, Volume 2, Issue 4, pp 227–250 | Cite as

Nanotechnology as Emerging Tool for Enhancing Solubility of Poorly Water-Soluble Drugs

  • Sandeep KumarEmail author
  • Neeraj Dilbaghi
  • Ruma Saharan
  • Gaurav Bhanjana


In the past few decades, nanotechnology has been used to develop various nano-based systems to facilitate the delivery of therapeutic and imaging agents for various medical applications. Nanoparticulate drug delivery systems have been used to modify and improve the pharmacokinetic and pharmacodynamics properties of various drugs used in therapeutic application. According to material of delivery vehicle used for the nanoparticles, they have been categorized as polymer-based nanoparticles, lipid-based nanoparticles, and lipid–polymer hybrid nanoparticles. Earlier, two types represent two primary delivery vehicles with lot of application in different fields but some intrinsic limitations remain to limit their application at certain extent. The later one have been demonstrated to include the unique advantages of both lipid-based nanoparticles and polymer-based nanoparticles while excluding some of their intrinsic limitations, thereby holding great promise as a delivery vehicle for various medical applications. In this review, we first introduce nanoparticles, method of preparation, and their types based on delivery vehicle followed by characteristics which affect the nanoparticle formulation. Finally, we summarize the potential medical application of the nanoparticles.


Polymer-based nanoparticles Lipid-based nanoparticles Lipid–polymer hybrid nanoparticles Zeta potential Drug loading and release Cellular uptake and cytotoxicity 


  1. 1.
    Lipinski, C. A., Lombardo, F., Dominy, B. W., Feeney, P. (1997). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 23, 3–25.CrossRefGoogle Scholar
  2. 2.
    Klopman, G., & Zhu, H. (2001). Estimation of aqueous solubility of organic molecules by the group contribution approach. Journal of Chemical Information and Computer Sciences, 41(2), 439–445. doi: 10.1021/ci000152d.Google Scholar
  3. 3.
    Brigger, I., Dubernet, C., Couvreur, P. (2002). Nanoparticles in cancer therapy and diagnosis. Advanced Drug Delivery Reviews, 54(5), 631–651. doi: 10.1016/S0169-409X(02)00044-3.CrossRefGoogle Scholar
  4. 4.
    Amidon, G. L., Lennernas, H., Shah, V. P., Crison, J. R. A. (1995). A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharmaceutical Research, 12(3), 413–419. doi: 10.1023/A:1016212804288.CrossRefGoogle Scholar
  5. 5.
    Yu, L. X., Amidon, G. L., et al. (2002). A biopharmaceutics classification system: the scientific basis for biowaiver extensions. Pharmaceutical Research, 19(7), 921–925. doi: 10.1023/A:101647360163.CrossRefGoogle Scholar
  6. 6.
    Gothoskar, A. V. (2005). Biopharmaceutical classification of drugs. Pharmacy Review. Available from: Accessed: 18 Jun 2012
  7. 7.
    Thiel-Demby, V. E., Humphreys, J. E., et al. (2009). Biopharmaceutics classification system: validation and learnings of an in vitro permeability assay. Molecular Pharmaceutics, 6(1), 11–18. doi: 10.1021/mp800122b.CrossRefGoogle Scholar
  8. 8.
    Chen, M., Amidon, G. L., Benet, L. Z., Lennernas, H., Yu, L. X. (2011). The BCS, BDDCS, and regulatory guidances. Pharmaceutical Research, 28(7), 1774–1778. doi: 10.1007/s11095-011-0438-1.CrossRefGoogle Scholar
  9. 9.
    Pouton, C. W. (2006). Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. European Journal of Pharmaceutical Sciences, 29(3–4), 278–287. doi: 10.1016/j.ejps.2006.04.016.CrossRefGoogle Scholar
  10. 10.
    Urbanetz, N. A. (2006). Stabilization of solid dispersions of nimodipine and polyethylene glycol 2000. The European Journal of Pharmaceutical Sciences, 28(1–2), 67–76. doi: 10.1016/j.ejps.2005.12.009.CrossRefGoogle Scholar
  11. 11.
    Noyes, A. A., & Whitney, W. R. (1897). The rate of solution of solid substances in their own solutions. Journal of the American Chemical Society, 19, 930–934. doi: 10.1021/ja02086a003.CrossRefGoogle Scholar
  12. 12.
    Liversidge, G., & Cundy, K. (1995). Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: I. Absolute oral bioavailability of nanocrystalline danazol in beagle dogs. International Journal of Pharmaceutics, 125, 91–97. doi: 10.1016/0378-5173(95)00122-Y.CrossRefGoogle Scholar
  13. 13.
    Benet, L. Z. (2008). Bioavailability and bioequivalence: focus on physiological factors and variability. Pharmaceutical Research, 25(8), 1956–1962. doi: 10.1007/s11095-008-9645-9.CrossRefGoogle Scholar
  14. 14.
    Tom, J. W., & Debenedetti, P. G. (1991). Particle formation with supercritical fluids—a review. Journal of Aerosol Science, 22(5), 555–584. doi: 10.1016/0021-8502(91)90013-8.CrossRefGoogle Scholar
  15. 15.
    Horn, D., & Rieger, J. (2001). Organic nanoparticles in the aqueous phase theory, experiment, and use. Angewandte Chemie (International Ed. in English), 40(23), 4330–4361. doi: 10.1002/1521-3773(20011203)40:23<4330::AID-ANIE4330>3.0.CO;2-W.CrossRefGoogle Scholar
  16. 16.
    Muller, R. H., Jacobs, C., Kayser, O. (2001). Nanosuspensions as particulate drug formulations in therapy: rationale for development and what we can expect in the future. Advanced Drug Delivery Reviews, 47(1), 3–19. doi: 10.1016/S0169-409X(00)00118-6.CrossRefGoogle Scholar
  17. 17.
    Rabinow, B. E. (2004). Nanosuspensions in drug delivery. Nature Reviews Drug Discovery, 3(9), 785–796. doi: 10.1038/nrd1494.CrossRefGoogle Scholar
  18. 18.
    Merisko-Liversidge, E., Liversidge, G. G., Cooper, E. R. (2004). Nanosizing: a formulation approach for poorly water-soluble compounds. European Journal of Pharmaceutical Sciences, 18(2), 113–120. doi: 10.1016/S0928-0987(02)00251-8.CrossRefGoogle Scholar
  19. 19.
    Suzuki, H., Ogawa, M., Hironaka, K., Ito, K., Sunada, H. (2001). A nifedipine coground mixture with sodium deoxycholate. II. Dissolution characteristics and stability. Drug Development International Pharmacy, 27(9), 951–958. doi: 10.1081/DDC-100107676.CrossRefGoogle Scholar
  20. 20.
    List, M., Sucker, H. (1998). Pharmaceutical colloidal hydrosols for injection. GB patent no. 2200048Google Scholar
  21. 21.
    Rogers, T. L., et al. (2002). A novel particle engineering technology: spray–freezing into liquid. International Journal of Pharmaceutics, 242(1–2), 93–100. doi: 10.1016/S0378-5173(02)00154-0.CrossRefGoogle Scholar
  22. 22.
    Hua, J., Keith, P., Johnston, B., Robert, O., Williams, A. (2004). Rapid dissolving high potency danazol powders produced by spray freezing into liquid process. International Journal of Pharmaceutics, 271, 145–154. doi: 10.1016/j.ijpharm.2003.11.003.CrossRefGoogle Scholar
  23. 23.
    Ribeiro, D. S., Richard, J. B. P., Thiesc, C., Benoit, J. P. (2002). Microencapsulation of protein particles within lipids using a novel supercritical fluid process. International Journal of Pharmaceutics, 242(1), 69–78. doi: 10.1016/S0378-5173(02)00149-7.CrossRefGoogle Scholar
  24. 24.
    Pathak, P., Meziani, M. J., Sun, Y.-P. (2005). Supercritical fluid technology for enhanced drug delivery. Expert Opinion on Drug Delivery, 2(4), 747–761. doi: 10.1517/17425247.2.4.747.CrossRefGoogle Scholar
  25. 25.
    Waard, H. D., Hinrichs, W. L. J., Frijlink, H. W. (2008). A novel bottom-up process to produce drug nanocrystals: controlled crystallization during freeze-drying. Journal of Controlled Release, 128(2), 179–183. doi: 10.1016/j.jconrel.2008.03.002.CrossRefGoogle Scholar
  26. 26.
    Pouton, C. W. (2000). Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and “self-microemulsifying” drug delivery systems. European Journal of Pharmaceutical Sciences, 11, 93–98. doi: 10.1016/S0928-0987(00)00167-6.CrossRefGoogle Scholar
  27. 27.
    Kawakami, K., Yoshikawa, T., Mororo, Y., Hayashi, T. (2002). Microemulsion formulation for enhanced absorption of poorly soluble drugs: I prescription design. Journal of Controlled Release, 81(1–2), 65–74. doi: 10.1016/S0168-3659(02)00049-4.CrossRefGoogle Scholar
  28. 28.
    Letchford, K., & Burt, H. (2007). A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymerosomes. European Journal of Pharmaceutics and Biopharmaceutics, 65, 259–269. doi: 10.1016/j.ejpb.2006.11.009.CrossRefGoogle Scholar
  29. 29.
    GuFX, K. R., WangAZ, A. F. E., et al. (2007). Targeted nanoparticles for cancer treatment. Nano Today, 2, 14–21. doi: 10.1016/S1748-0132(07)70083-X.CrossRefGoogle Scholar
  30. 30.
    Tong, R., & Cheng, J. J. (2007). Anticancer polymeric nanomedicines. Polymer Reviews, 47, 345–381. doi: 10.1080/15583720701455079.CrossRefGoogle Scholar
  31. 31.
    Torchilin, V. P. (2005). Recent advances with liposomes as pharmaceutical carriers. Nature Reviews. Drug Discovery, 4(2), 145–160. doi: 10.1038/nrd1632.CrossRefGoogle Scholar
  32. 32.
    Torchilin, V. P. (2007). Micellar nanocarriers: pharmaceutical perspectives. Pharmaceutical Research, 24(1), 1–16. doi: 10.1007/s11095-006-9132-0.CrossRefGoogle Scholar
  33. 33.
    Merisko-Liversidge, E. M., & Liversidge, G. G. (2008). Drug nanoparticles: formulating poorly water-soluble compounds. Toxicologic Pathology, 36(1), 43–48. doi: 10.1177/0192623307310946.CrossRefGoogle Scholar
  34. 34.
    Hu, J., Johnston, K. P., Williams, R. O. (2004). Nanoparticle engineering processes for enhancing the dissolution rates of poorly water soluble drugs. Drug Development and Industrial Pharmacy, 30(3), 233–245. doi: 10.1081/DDC-120030422.CrossRefGoogle Scholar
  35. 35.
    Jani, P. U., Florence, A. T., McCarthy, D. E. (1992). Further histologicalevidence of the gastrointestinal absorption of polystyrene nanospheres in the rat. International Journal of Pharmaceutics, 84, 245–252. doi: 10.1016/0378-5173(92)90162-U.CrossRefGoogle Scholar
  36. 36.
    Hillery, A. M., & Florence, A. T. (1996). The effect of adsorbed poloxamer 188 and 407 surfactants on the intestinal uptake of 60 nm polystyrene particles after oral administration in the rat. International Journal of Pharmaceutics, 132, 123–130. doi: 10.1016/0378-5173(95)04353-5.CrossRefGoogle Scholar
  37. 37.
    Rajput, G., Majmudar, F., Patel, J., Thakor, R., Rajqor, N. B. (2010). Stomach-specific mucoadhesive microsphere as a controlled drug delivery system. Systemic Reviews in Pharmacy, 1(1), 70–78. doi: 10.4103/0975-8453.59515.CrossRefGoogle Scholar
  38. 38.
    Peters, K., & Muller, R. H. (1998). Nanosuspensions for the formulation of poorly soluble drugs: I. Preparation by a size-reduction technique. International Journal of Pharmaceutics, 160(2), 229–237. doi: 10.1016/S0378-5173(97)00311-6.CrossRefGoogle Scholar
  39. 39.
    Langguth, P., Hanafy, A., Frenzel, D., Grenier, P., et al. (2005). Nanosuspension formulationsfor low-soluble drugs: pharmacokinetic evaluation using spironolactone as model compound. Drug Development & Industry Pharmacy, 31(3), 319–321. doi: 10.1081/DDC-52182.Google Scholar
  40. 40.
    Kocbek, P., Baumgartner, S., Kristl, J. (2006). Preparation and evaluationof nanosuspensions for enhancing the dissolution of poorly water-soluble drugs. International Journal of Pharmaceutics, 312(1–2), 179–186. doi: 10.1016/j.ijpharm.2006.01.008.CrossRefGoogle Scholar
  41. 41.
    Horter, D., & Dressman, J. B. (2001). Influence of physicochemical propertieson dissolution of drugs in the gastrointestinal tract. Advanced Drug Delivery Reviews, 46(1–3), 75–87. doi: 10.1016/S0169-409X(00)00130-7.CrossRefGoogle Scholar
  42. 42.
    Mamo, T., Moseman, E. A., Kolishetti, N., Salvador-Morales, C., et al. (2010). Emerging nanotechnology approaches for HIV/AIDS treatment and prevention. Nanomedicine, 5(2), 269–285. doi: 10.2217/nnm.10.1.CrossRefGoogle Scholar
  43. 43.
    Hanel, J. (2010). Biodegradable nanosized particles to deliver sustained-release medication cargo. Nanomedicine: nanomateral. PNAS, 2009(106), 19268–19273. Published online:; The A to Z of nanotechnology.Google Scholar
  44. 44.
    Soutter, W. (2012). Nanotechnology-based cancer treatment can reduce side effects. Nanomedicine: nanomateral. Published online. Available at: Last accessed on 25 Jun 2012
  45. 45.
    Zhang, L., & Zhang, L. G. (2010). Lipid-polymer hybrid nanoparticles: synthesis, characterization and application. Nano LIFE, 1(1–2), 163–173. doi: 10.1142/S179398441000016X.CrossRefGoogle Scholar
  46. 46.
    Mahapatro, A., & Singh, D. K. (2011). Biodegradable nanoparticles are excellent vehicle for site directed in vivo delivery of drugs and vaccines. Journal of Nanobiotechnology, 9, 55–67. doi: 10.1186/1477-3155-9-55.CrossRefGoogle Scholar
  47. 47.
    Jong, W. H. D., & Borm, P. J. A. (2008). Drug delivery and nanoparticles: applications and hazards. International Journal of Nanomedicine, 3(1), 133–149 PMCID: PMC2527668.CrossRefGoogle Scholar
  48. 48.
    BormPJ, M.-S. D. (2006). Nanoparticles in drug delivery and environmental exposure: same size, same risk? Nanomedicine, 1(2), 235–249. doi: 10.2217/17435889.1.2.235.CrossRefGoogle Scholar
  49. 49.
    Labhasetwar, V., Song, C., Levy, R. J. (1997). Nanoparticle drug delivery system forrestenosis. Advanced Drug Delivery Reviews, 24(1), 63–85. doi: 10.1016/S0169-409X(96)00483-8.CrossRefGoogle Scholar
  50. 50.
    Langer, R. (2000). Biomaterials in drug delivery and tissue engineering: one laboratory’s experience. Accounts of Chemical Research, 33(2), 94–101. doi: 10.1021/ar9800993.CrossRefGoogle Scholar
  51. 51.
    Bhadra, D., Bhadra, S., Jain, P., Jain, N. K. (2003). A PEGylated dendritic nanoparticulate carrier of fluorouracil. International Journal of Pharmaceutics, 257(1–2), 111–124. doi: 10.1016/S0378-5173(03)00132-7.CrossRefGoogle Scholar
  52. 52.
    Kommareddy, S., Tiwari, S. B., Amiji, M. M. (2005). Long-circulating polymeric nanovectors for tumor-selective gene delivery. Technology in Cancer Research & Treatment, 4(6), 615–625.Google Scholar
  53. 53.
    Hans, M. L., & Lowman, A. M. (2002). Biodegradable nanoparticles for drug delivery and targeting. Current Opinion in Solid State and Materials Science, 6(4), 319–327. doi: 10.1016/S1359-0286(02)00117-1.CrossRefGoogle Scholar
  54. 54.
    Sonia, T. A., & Sharma, C. P. (2011). Chitosan and its derivatives for drug delivery perspective. Advances in Polymer Science, 243, 23–54. doi: 10.1007/12_2011_117.CrossRefGoogle Scholar
  55. 55.
    Ubrich, N., Schmidt, C., Bodmeier, R., Hoffman, M., Maincent, P. (2005). Oral evaluation in rabbits of cyclosporin-loaded Eudragit RS or RL nanoparticles. International Journal of Pharmaceutics, 288(1), 169–175. doi: 10.1016/j.ijpharm.2004.09.019.CrossRefGoogle Scholar
  56. 56.
    Illum, L. (1998). Chitosan and its use as a pharmaceutical excipient. Pharmaceutical Research, 15, 1326–1331. doi: 10.1023/A:1011929016601.CrossRefGoogle Scholar
  57. 57.
    Kreuter, J. (1994). Nanoparticles. In J. Kreuter (Ed.), Colloidal drug delivery systems (pp. 261–276). New York: Marcel Dekker.Google Scholar
  58. 58.
    Muller, R. H. (1991). Colloidal carriers for controlled drug delivery and targeting, modification, characterization and in vivo distribution. Boston: CRC Press.Google Scholar
  59. 59.
    Agnihotri, S. A., Mallikarjuna, N. N., Aminabhavi, T. M. (2004). Recent advances on chitosan-based micro- and nanoparticles in drug delivery. Journal of Controlled Release, 100(1), 5–28. doi: 10.1016/j.jconrel.2004.08.010.CrossRefGoogle Scholar
  60. 60.
    Prabaharan, M., & Mano, J. F. (2005). Chitosan-based particles as controlled drug delivery systems. Drug Delivery, 12(1), 41–57. doi: 10.1080/10717540590889781.CrossRefGoogle Scholar
  61. 61.
    Aspden, T. J., Mason, J. D., Jones, N. S. (1997). Chitosan as a nasal delivery system: the effect of chitosan solutions on in vitro and in vivo mucociliary transport rates in human turbinates and volunteers. Journal of Pharmaceutical Sciences, 86(4), 509–513. doi: 10.1021/js960182o.CrossRefGoogle Scholar
  62. 62.
    Mao, H. Q., Troung-le, V. L., Janes, K. A., Roy, K., Wang, Y., August, J. T., Leong, K. W. (2001). Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. Journal of Controlled Release, 70(3), 399–421. doi: 10.1016/S0168-3659(00)00361-8.CrossRefGoogle Scholar
  63. 63.
    Wang, X., Chi, N., Tang, X. (2008). Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting. European Journal of Pharmaceutics and Biopharmaceutics, 70(3), 735–740. doi: 10.1016/j.ejpb.2008.07.005.CrossRefGoogle Scholar
  64. 64.
    Calvo, et al. (1997). Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers. Journal of Applied Polymer Science, 63, 125–132. doi: 0021-8995/97/010125-08.CrossRefGoogle Scholar
  65. 65.
    Bodmeier, R., Chen, H. G., Paeratakul, O. (1989). A novel approach to the oral delivery of micro- or nanoparticles. Pharmaceutical Research, 6(5), 413–417. doi: 10.1023/A:1015987516796.CrossRefGoogle Scholar
  66. 66.
    Pan, Y., Li, Y. J., Zhao, H. Y., Zheng, J. M., Xu, H., Wei, G., Hao, J. S., Cui, F. D. (2002). Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo. International Journal of Pharmaceutics, 249(1–2), 139–147. doi: 10.1016/S0378-5173(02)00486-6.CrossRefGoogle Scholar
  67. 67.
    Dustgani, A., Fasahani, E. V., Imani, M. (2012). Preparation and in vitro characterization of chitosan nanoparticles containing Mesobuthus eupeus scorpion venom as an antigen delivery system. Journal of Venomous Animals and Toxins including Tropical Diseases, 18(1), 44–52. doi: 10.1590/S1678-91992012000100006.Google Scholar
  68. 68.
    Shi, L. E., & Tang, Z. X. (2007). Adsorption of nuclease p1 on chitosan nano-particles. Brazilian Journal of Chemical Engineering, 26(2), 223–228. doi: 10.1590/S0104-66322009000200022.Google Scholar
  69. 69.
    Gan, Q., Wang, T., Cochrane, C., McCarron, P. (2005). Modulation of surface charge, particle size and morphological properties of chitosan–TPP nanoparticles intended for gene delivery. Colloids and Surfaces B, 44(2–3), 65–73. doi: 10.1016/j.colsurfb.2005.06.001.CrossRefGoogle Scholar
  70. 70.
    Tsai, M. L., Bai, S. W., Chen, R. H. (2008). Cavitation effects versus stretch effects resulted in different size and polydispersity of ionotropic gelation chitosan-sodium tripolyphosphate nanoparticle. Carbohydrate Polymers, 71(3), 448–457.CrossRefGoogle Scholar
  71. 71.
    López-León, T., Carvalho, E. L., Seijo, B., Ortega-Vinuesa, J. L., Bastos-González, D. (2005). Physicochemical characterization of chitosan nanoparticles: electrokinetic and stability behavior. Journal of Colloid and Interface Science, 283(2), 344–351. doi: 10.1016/j.jcis.2004.08.186.CrossRefGoogle Scholar
  72. 72.
    Sarmento, B., Ribeiro, A. J., Veiga, F., Ferreira, D. (2007). Alginate/chitosan nanoparticles are effective for oral insulin delivery. Pharmaceutical Research, 24(12), 2198–2206. doi: 10.1007/s11095-007-9367-4.CrossRefGoogle Scholar
  73. 73.
    Vila, A., Sánchez, A., Janes, K., Behrens, I., Kissel, T., Vila Jato, J. L., Alonso, M. J. (2004). Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice. The European Journal of Pharmaceutical, 57(1), 123–131. doi: 10.1016/j.ejpb.2003.09.006.CrossRefGoogle Scholar
  74. 74.
    Fernandez-Urrusuno, R., Calvo, P., Remunan-Lopez, C., Vila-Jato, J. L., Alonso, M. J. (1999). Enhancement of nasal absorbtion of insulin using chitosan nanoparticles. Pharmaceutical Research, 16, 1576–1581. doi: 10.1023/A:1018908705446.CrossRefGoogle Scholar
  75. 75.
    Aktas, Y., Andrieux, K., Alonso, M. J., Calvo, P., Gürsoy, R. N., Couvreur, P., Capan, Y. (2005). Preparation and in vitro evaluation of chitosan nanoparticles containing a caspase inhibitor. International Journal of Pharmaceutics, 298, 378–383. doi: 10.1016/j.ijpharm.2005.03.027.CrossRefGoogle Scholar
  76. 76.
    DeCampos, A. M., & Alonso, M. J. (2001). Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface: application to cyclosporine A. International Journal of Pharmaceutics, 224(1–2), 116–159. doi: 10.1016/S0378-5173(01)00760-8.Google Scholar
  77. 77.
    Shu, X. Z., & Zhu, K. J. (2000). A novel approach to prepare tripolyphosphate/chitosan complex beads for controlled release drug delivery. International Journal of Pharmaceutics, 201(1), 51–58. doi: 10.1016/S0378-5173(00)00403-8.CrossRefGoogle Scholar
  78. 78.
    Cetin, M., Atila, A., Kadioglu, Y. (2010). Formulation and in vitro characterization of Eudragit® L100 and Eudragit® L100-PLGA nanoparticles containing diclofenac sodium. AAPS PharmSciTech, 11(3), 1250–1256. doi: 10.1208/s12249-010-9489-6.CrossRefGoogle Scholar
  79. 79.
    Avadi, M. R., Sadeghi, A. M. M., Mohammadpour, N., et al. (2010). Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method. Nanomedicine: Nanotechnology, Biology and Medicine, 6(1), 58–63. doi: 10.1016/j.nano.2009.04.007.CrossRefGoogle Scholar
  80. 80.
    Maitra, A. N., Ghosh, P. K., De, T. K., Sahoo, S. K. (1999) Process for the preparation of highly monodispersed hydrophilic polymeric nanoparticles of size less than 100 nm. US patent 5,874,111.Google Scholar
  81. 81.
    Ohya, Y., Shiratani, M., Kobayashi, H., Ouchi, T. (1993). Release behavior of 5-fluorouracil from chitosan-gel nanospheres immobilizing 5-fluorouracil coated with polysaccharides and their cell specific cytotoxicity. Journal of Microencapsulation, 10(1), 1–9. doi: 10.3109/02652049309015307.CrossRefGoogle Scholar
  82. 82.
    Goldberg, M., Langer, R., Jia, X. (2007). Nanostructured materials for applications in drug delivery and tissue engineering. Journal of Biomaterials Science, Polymer Edition, 18(3), 241–268. doi: 10.1163/156856207779996931.CrossRefGoogle Scholar
  83. 83.
    Mitra, S., Gaur, U., Ghosh, P. C., Maitra, A. N. (2001). Tumour targeted delivery of encapsulated dextran–doxorubicin conjugate using chitosan nanoparticles as carrier. Journal of Controlled Release, 74(1–3), 317–323. doi: 10.1016/S0168-3659(01)00342-X.CrossRefGoogle Scholar
  84. 84.
    Qu, J., Liu, G., Wang, Y., Hong, R. (2010). Preparation of Fe3O4-chitosan nanoparticles used for hyperthermia. Advanced Powder Technology, 21(4), 461–467. doi: 10.1016/j.apt.2010.01.008.CrossRefGoogle Scholar
  85. 85.
    Denuziere, A., Ferrier, D., Damour, O., Domard, A. (1998). Chitosan–chondroitin sulfate and chitosan–hyaluronate polyelectrolyte complexes: biological properties. Biomaterials, 19(14), 1275–1285. doi: 10.1016/S0142-9612(98)00036-2.CrossRefGoogle Scholar
  86. 86.
    Chen, Y., Mohanraj, V. J., Parkin, J. E. (2003). Chitosan-dextran sulfate nanoparticles for delivery of an anti-angiogenesis peptide. International Journal of Peptide Research and Therapeutics, 10(5–6), 621–629. doi: 10.1007/s10989-004-2433-4.CrossRefGoogle Scholar
  87. 87.
    Chen, Y., Mohanraj, V. J., Wang, F., Benson, H. A. E. (2007). Designing chitosan-dextran sulfate nanoparticles using charge ratios. AAPS PharmSciTech, 8(4), 131–139. doi: 10.1208/pt0804098.CrossRefGoogle Scholar
  88. 88.
    Ichikawa, S., Iwamoto, S., Watanabe, J. (2005). Formation of biocompatible nanoparticles by self-assembly of enzymatic hydrolysates of chitosan and carboxymethyl cellulose. Bioscience, Biotechnology, and Biochemistry, 69(9), 1637–1642. doi: 10.1271/bbb.69.1637.CrossRefGoogle Scholar
  89. 89.
    Liu, Z., Jiao, Y., Liu, F., Zhang, Z. (2007). Heparin/chitosan nanoparticle carriers prepared by polyelectrolyte complexation. Journal of Biomedical Materials Research Part A, 83(3), 806–812. doi: 10.1002/jbm.a.31407.CrossRefGoogle Scholar
  90. 90.
    Tan, Q., Tang, H., Hu, J., Hu, Y., Zhou, X., Tao, Y., Wu, Z. (2011). Controlled release of chitosan/heparin nanoparticle-delivered VEGF enhances regeneration of decellularized tissue-engineered scaffolds. International Journal of Nanomedicine, 6, 929–942. doi: 10.2147/IJN.S18753.CrossRefGoogle Scholar
  91. 91.
    Tiyaboonchai, W., & Limpeanchob, N. (2007). Formulation and characterization of amphotericin B-chitosan-dextran sulfate nanoparticles. International Journal of Pharmaceutics, 329(1–2), 142–149. doi: 10.1016/j.ijpharm.2006.08.013.CrossRefGoogle Scholar
  92. 92.
    Erbacher, P., Zou, S., Bettinger, T., Steffan, A. M., Remy, J. S. (1998). Chitosan-based vector/DNA complexes for gene delivery: biophysical characteristics and transfection ability. Pharmaceutical Research, 15(9), 1332–1339. doi: 10.1023/A:1011981000671.CrossRefGoogle Scholar
  93. 93.
    Sarmento, B., Martins, S., Ribeiro, A., Veiga, F., Neufeld, R., Ferreira, D. (2006). Development and comparison of different nanoparticulate polyelectrolyte complexes as insulin carriers. The International Journal of Peptide Research and Therapeutics, 12(2), 131–138. doi: 10.1007/s10989-005-9010-3.CrossRefGoogle Scholar
  94. 94.
    Sadeghi, A. M., Dorkoosh, F. A., Avadi, M. R., Weinhold, M., et al. (2008). Permeation enhancer effect of chitosan and chitosan derivatives: comparison of formulations as soluble polymers and nanoparticulate systems on insulin absorption in Caco-2 cells. European Journal of Pharmaceutics and Biopharmaceutics, 70(1), 270–278. doi: 10.1016/j.ejpb.2008.03.004.CrossRefGoogle Scholar
  95. 95.
    Coppi, G., Iannuccelli, V., Leo, E., Bernabei, M. T., Cameroni, R. (2001). Chitosan-alginate microparticles as a protein carrier. Drug Development and Industrial Pharmacy, 27(5), 393–400. doi: 10.1081/DDC-100104314.CrossRefGoogle Scholar
  96. 96.
    Douglas, K. L., & Tabrizian, M. (2005). Effect of experimental parameters on the formation of alginate-chitosan nanoparticles and evaluation of their potential application as DNA carrier. Journal of Biomaterials Science, 16(1), 43–56. doi: 10.1163/1568562052843339.CrossRefGoogle Scholar
  97. 97.
    Sarmento, B., Ferreira, D., Veiga, F., Ribeiro, A. (2006). Characterization of insulin-loaded alginate nanoparticles produced by ionotropic pre-gelation through DSC and FTIR studies. Carbohydrate Polymers, 66, 1–7. doi: 10.1016/j.carbpol.2006.02.008.CrossRefGoogle Scholar
  98. 98.
    Zhang, Y., Yang, W., Wang, C., Hu, J., Fu, S., Dong, L., Wu, L., Shen, X. (2007). Nanoparticles based on the complex of chitosan and polyaspartic acid sodium salt: preparation, characterization and the use for 5-fluorouracil delivery. European Journal of Pharmaceutics and Biopharmaceutics, 67, 621–631. doi: 10.1016/j.ejpb.2007.04.007.CrossRefGoogle Scholar
  99. 99.
    Zhang, D. Y., Shen, X. Z., Wang, J. Y., Dong, L., Zheng, Y. L., Wu, L. L. (2008). Preparation of chitosan-polyaspartic acid-5-fluorouracil nanoparticles and its anti-carcinoma effect on tumor growth in nude mice. World Journal of Gastroenterology, 14, 3554–3562. doi: 10.3748/wjg.14.3554.CrossRefGoogle Scholar
  100. 100.
    Lee, J. E., Khan, S. A., Lim, K. H. Chitosan-nanoparticle preparationby polyelectrolyte complexation. 1-2. Available online:,%20Eun-Ju%20%28Kyungpook%20Nat.U.,%20Daegu,%20Korea%29%20%20541.pdf. Accessed: 23 Jun 2012
  101. 101.
    Mourao, P. A. S., & Pereira, M. S. (1999). Searching for alternatives to heparin: sulfated fucans from marine invertebrates. Trends in Cardiovascular Medicine, 9, 225–232. doi: 10.1016/S1050-1738(00)00032-3.CrossRefGoogle Scholar
  102. 102.
    Mi, F. L., Shyu, S. S., Kuan, C. Y., Lee, S. L., Lu, K. T., Jang, S. F. (1999). Chitosan–polyelectrolyte complexation for the preparation of gel beads and controlled release of anticancer drug. II. Effect of pH-dependent ionic crosslinking or interpolymer complex using tripolyphosphate or polyphosphate as reagent. Journal of Applied Polymer Science, 74, 1093–1107. doi: 10.1002/(SICI)1097-4628(19991114)74:7<1868::AID-APP32>3.0.CO;2-N.CrossRefGoogle Scholar
  103. 103.
    Singla, A. K., & Chawla, M. (2001). Chitosan: some pharmaceutical and biological aspects—an update. The Journal of Pharmacy and Pharmacology, 53(8), 1047–1067. doi: 10.1211/0022357011776441.CrossRefGoogle Scholar
  104. 104.
    Tapia, C., Escobar, Z., Costa, E., Sapag-Hagar, J., Valenzuela, F., Basualto, C., Nella, G. M., Yazdano-Pedram, M. (2004). Comparative studies on polyelectrolyte complexes and mixtures of chitosan-alginate and chitosan-carrageenan as prolonged diltiazemclorhydrate release systems. European Journal of Pharmaceutics and Biopharmaceutics, 57(1), 65–75. doi: 10.1016/S0939-6411(03)00153-X.CrossRefGoogle Scholar
  105. 105.
    Vila, A., Sanchez, A., Janes, K., Behrens, I., Kissel, T., Vila-Jato, J. L., Alonso, M. J. (2004). Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice. European Journal of Pharmaceutics and Biopharmaceutics, 57(1), 123–131. doi: 10.1016/j.ejpb.2003.09.006.CrossRefGoogle Scholar
  106. 106.
    Borchard, G. (2001). Chitosan for gene delivery. Advanced Drug Delivery Reviews, 52(2), 145–150. doi: 10.1016/S0169-409X(01)00198-3.CrossRefGoogle Scholar
  107. 107.
    Thanou, M., Florea, B., Geldof, M., Junginger, H. E., Borchard, G. (2002). Quaternized chitosan oligomers as novel gene delivery vectors in epithelial cell lines. Biomaterials, 23(1), 153–159. doi: 10.1016/S0142-9612(01)00090-4.CrossRefGoogle Scholar
  108. 108.
    Nagasaki, T., Hojo, M., Uno, A., Satch, T., Koumoto, K., Mizu, M., Sakurai, K., Shinkai, S. (2004). Long-term expressionwith a cationic polymer derived from a natural polysaccharide: schizophyllan. Bioconjugate Chemistry, 15(2), 249–259. doi: 10.1021/bc034178x.CrossRefGoogle Scholar
  109. 109.
    Mansouri, S., Lavigne, P., Corsi, K., Benderdour, M., Beaumont, E., Fernandes, J. C. (2004). Chitosan–DNA nanoparticles as non-viral vectors in gene therapy: strategies to improve transfection efficiency. European Journal of Pharmaceutics and Biopharmaceutics, 57(1), 1–8. doi: 10.1016/S0939-6411(03)00155-3.CrossRefGoogle Scholar
  110. 110.
    Sashiwa, H., Thompson, J. M., Das, S. K., Shigenasa, Y., Tripathy, S., Roy, R. (2000). Chemical modification of chitosan: binding proprieties of a-galactosyl-chitosan conjugates. Potential inhibitors in acute rejection following xeno-transplantation. Biomolecules, 1(3), 303–305. doi: 10.1021/bm005536r.Google Scholar
  111. 111.
    Sharma, A., Mondal, K., Gupta, M. N. (2003). Separation of enzymes by sequential macroaffinity ligand-facilitated three-phase partitioning. Journal of Chromatography A, 995(1&2), 127–134. doi: 10.1016/S0021-9673(03)00522-3.CrossRefGoogle Scholar
  112. 112.
    Sasaki, C., Kristiansen, A., Fukamizo, T., Varum, K. M. (2003). Biospecific fractionation of chitosan. Biomolecules, 4(6), 1686–1690. doi: 10.1021/bm034124q.Google Scholar
  113. 113.
    Park, S. I., & Zhao, Y. (2004). Incorporation of a high concentration of mineral or vitamin into chitosan-based films. Journal of Agricultural and Food Chemistry, 52(7), 1933–1939. doi: 10.1021/jf034612p.CrossRefGoogle Scholar
  114. 114.
    Silva, C. L., Pereira, J. C., Ramalho, A., Pais, A. A. C. C., Sousa, J. S. J. (2008). Films based on chitosan polyelectrolyte complexes for skin drug delivery: development and characterisation. Journal of Membrane Science, 320, 268–279. doi: 10.1016/j.memsci.2008.04.011.CrossRefGoogle Scholar
  115. 115.
    Ruel-Gariepy, E., Chenite, A., Chaput, C., Guirguis, S., Lerous, J. (2000). Characterization of thermosensitive chitosan gels for the sustained delivery of drugs. International Journal of Pharmaceutics, 203(1–2), 89–98. doi: 10.1016/S0378-5173(00)00428-2.CrossRefGoogle Scholar
  116. 116.
    Ramanathan, S., & Block, L. H. (2001). The use of chitosan gels as matrices for electrically-modulated drug delivery. Journal of Controlled Release, 70(1–2), 109–123. doi: 10.1016/S0168-3659(00)00333-3.CrossRefGoogle Scholar
  117. 117.
    Vinogradov, S. V., Bronich, T. K., Kabanow, A. V. (2002). Synthesis of nanogel carrier for delivery of active phosphorylated nucleoside analogues. Advanced Drug Delivery Reviews, 54(1), 135–147.CrossRefGoogle Scholar
  118. 118.
    Kofuji, K., Akamine, H., Qian, C. J., Watanaba, K., Togan, Y., Nishimura, M., Sugiyana, I., Murata, Y., Kawashima, S. (2004). Therapeutic efficacy of sustained drug release from chitosan gel on local inflammation. International Journal of Pharmaceutics, 272(1–2), 65–78. doi: 10.1016/j.ijpharm.2003.11.036.CrossRefGoogle Scholar
  119. 119.
    Bergera, J., Reista, M., Mayera, J. M., Feltb, O., Gurny, R. (2004). Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications. European Journal of Pharmaceutics and Biopharmaceutics, 57(1), 35–52. doi: 10.1016/S0939-6411(03)00160-7.CrossRefGoogle Scholar
  120. 120.
    El-Shabouri, M. H. (2002). Positively charged nanoparticles for improving the oral bioavailability of cyclosporin-A. International Journal of Pharmaceutics, 249, 101–108. doi: 10.1016/S0378-5173(02)00461-1.CrossRefGoogle Scholar
  121. 121.
    Niwa, T., Takeuchi, H., Hino, T., Kunou, N., Kawashima, Y. (1994). In vitro drug release behavior of d, l-lactide/glycolide copolymer (PLGA) nanospheres with nafarelin acetate prepared by a novel spontaneous emulsification solvent diffusion method. Journal of Pharmaceutical Sciences, 83(5), 727–732. doi: 10.1002/jps.2600830527.CrossRefGoogle Scholar
  122. 122.
    Lim, S. T., Martin, G. P., Berry, D. J., Brown, M. B. (2000). Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan. Journal of Controlled Release, 66(2–3), 281–292. doi: 10.1016/S0168-3659(99)00285-0.CrossRefGoogle Scholar
  123. 123.
    Jaganathan, K. S., Rao, Y. U., Singh, P., Prabakaran, D., Gupta, S., Jain, A., Vyas, S. P. (2005). Development of a single dose tetanus toxoid formulation based on polymeric microspheres: a comparative study of poly(d, l-lactic-co-glycolic acid) versus chitosan microspheres. International Journal of Pharmaceutics, 294(1–2), 23–32. doi: 10.1016/j.ijpharm.2004.12.026.CrossRefGoogle Scholar
  124. 124.
    Tønnesen, H. H., & Karlsen, J. (2002). Alginate in drug delivery systems. Drug Development and Industrial Pharmacy, 28(6), 621–630. doi: 10.1081/DDC-120003853.CrossRefGoogle Scholar
  125. 125.
    Rajaonarivony, M., Vauthier, C., Couarraze, G., Puisieux, F., Couvreur, P. (1993). Development of a new drug carrier made from alginate. Journal of Pharmaceutical Sciences, 82(8), 912–917. doi: 10.1002/jps.2600820909.CrossRefGoogle Scholar
  126. 126.
    Pandey, R., Ahmad, Z., Sharma, S., Khuller, G. K. (2005). Nano-encapsulation of azole antifungals: potential applications to improve oral drug delivery. International Journal of Pharmaceutics, 301(1–2), 268–276. doi: 10.1016/j.ijpharm.2005.05.027.CrossRefGoogle Scholar
  127. 127.
    Hoa, L. T. M., Chi, N. T., Triet, N. M., Nhan, L. N. T., Chien, D. M. (2009). Preparation of drug nanoparticles by emulsion evaporation method. Journal of Physics Conference Series, 187, 1–4. doi: 10.1088/1742-6596/187/1/012047.Google Scholar
  128. 128.
    Bungenberg de Jong, H. G. (1949). A survey of the study objects in this volume. In H. R. Kruyt (Ed.), Colloid science vol II (pp. 1–18). Amsterdam: Elsevier.Google Scholar
  129. 129.
    Okhamafe, A. O., Amsden, B., Chu, W., Goosen, M. F. A. (1996). Modulation of protein release from chitosan-alginate microcapsules using pH- sensitive polymer hydroxypropyl methylcellulose acetate succinate. Journal of Microencapsulation, 13(5), 497–508. doi: 10.3109/02652049609026035.CrossRefGoogle Scholar
  130. 130.
    Mooren, F. C., & Berthold, A. (1998). Influence of chitosan microspheres on the transport of prednisone sodium phosphate across HT-29 cell monolayers. Pharmaceutical Research, 15(1), 58–65. doi: 10.1023/A:1011996619500.CrossRefGoogle Scholar
  131. 131.
    Sonvico, F., Cagnani, A., Rossi, A., Motta, S., Di Bari, M. T., Cavatorta, F., Alonso, M. J., Deriu, A., et al. (2006). Formation of self-organized nanoparticles by lecithin/chitosan ionic interaction. The International Journal of Pharmaceutics, 324(1), 67–73. doi: 10.1016/j.ijpharm.2006.06.036.CrossRefGoogle Scholar
  132. 132.
    Leong, K. W., Mao, H. Q., Truong-Le, V. L., Roy, K., Walsh, S. M., August, J. T. (1998). DNA-polycation nanospheres as non-viral gene delivery vehicles. Journal of Controlled Release, 53(1–3), 183–193. doi: 10.1016/S0168-3659(97)00252-6.CrossRefGoogle Scholar
  133. 133.
    Roy, K., Mao, H. Q., Huang, S. K., Leong, K. W. (1999). Oral gene delivery with chitosan–DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nature Medicine, 5(4), 387–391. doi: 10.1038/7385.CrossRefGoogle Scholar
  134. 134.
    Bhattarai, N., Ramay, H. R., Chou, S. H., Zhang, M. (2006). Chitosan and lactic acid-grafted chitosan nanoparticles as carriers for prolonged drug delivery. International Journal of Nanomedicine, 1(2), 181–187. doi: 10.2147/nano.2006.1.2.18.CrossRefGoogle Scholar
  135. 135.
    Tien, C. L., Lacroix, I.-S. P., Mateescu, M. A. (2003). N-acylated chitosan: hydrophobic matrices for controlled drug release. Journal of Controlled Release, 93(1), 1–13. doi: 10.1016/S0168-3659(03)00327-4.CrossRefGoogle Scholar
  136. 136.
    Yoo, H. S., Lee, J. E., Chung, H., Kwon, I. C., Jeong, S. Y. (2005). Self -assembled nanoparticles containing hydrophobically modified glycol chitosan for gene delivery. Journal of Controlled Release, 103(1), 235–243. doi: 10.1016/j.jconrel.2004.11.033.CrossRefGoogle Scholar
  137. 137.
    Park, J. H., Kwon, S., Nam, J. O., et al. (2005). Self-assembled nanoparticles based on glycol chitosan bearing 5 β-cholanic acid for RGD peptide delivery. Journal of Controlled Release, 95(3), 579–588. doi: 10.1016/j.jconrel.2003.12.020.CrossRefGoogle Scholar
  138. 138.
    Zhang, J., Chen, X. G., Li, Y. Y., Liu, C. S. (2007). Self-assembled nanoparticles based on hydrophobically modified chitosan as carriers for doxorubicin. Nanomedicine, 3(4), 258–265. doi: 10.1016/j.nano.2007.08.002.CrossRefGoogle Scholar
  139. 139.
    Kim, J. H., Kim, Y. S., Park, K., et al. (2008). Antitumor efficacy of cisplatin-loaded glycol chitosan nanoparticles in tumor-bearing mice. Journal of Controlled Release, 127(1), 41–49. doi: 10.1016/j.jconrel.2007.12.014.CrossRefGoogle Scholar
  140. 140.
    Chen, C. C., Tsai, T. H., Huang, Z. R., Fang, J. F. (2010). Effects of lipophilic emulsifiers on the oral administration of lovastatin from nanostructured lipid carriers: physicochemical characterization and pharmacokinetics. European Journal of Pharmaceutics and Biopharmaceutics, 74(3), 474–482. doi: 10.1016/j.ejpb.2009.12.008.CrossRefGoogle Scholar
  141. 141.
    Müller, R. H., Petersen, R. D., Hommoss, A., Pardeike, J. (2007). Nanostructured lipid carriers (NLC) in cosmetic dermal products. Advanced Drug Delivery Reviews, 59(6), 522–530. doi: 10.1016/j.addr.2007.04.012.CrossRefGoogle Scholar
  142. 142.
    Mo, Y., & Lim, L. (2004). Mechanistic study of the uptake of wheat germ agglutinin-conjugated PLGA nano particles by A549 cells. Journal of Pharmaceutical Sciences, 93(1), 20–28. doi: 10.1002/jps.10507.CrossRefGoogle Scholar
  143. 143.
    Yeh, T. K., Lu, Z., Wientjes, M. G., Au, J. L.-S. (2005). Formulating paclitaxel in nanoparticles alters its disposition. Pharmaceutical Research, 22(6), 867–874. doi: 10.1007/s11095-005-4581-4.CrossRefGoogle Scholar
  144. 144.
    Stevens, P. J., Sekido, M., Lee, R. J. (2004). Synthesis and evaluation of a hematoporphyrin derivative in a folate receptor-targeted solid–lipid nanoparticle formulation. Anticancer Research, 24(1), 161–165. doi: 0250-7005/2004$2.00+.40.Google Scholar
  145. 145.
    Stevens, P. J., Sekido, M., Lee, R. J. (2004). A folate receptor-targeted lipid nanoparticle formulation for a lipophilic paclitaxel prodrug. Pharmaceutical Research, 21(12), 2153–2157. doi: 10.1007/s11095-004-7667-5.CrossRefGoogle Scholar
  146. 146.
    Wu, J., Xiaobin, Z., Lee, R. J. (2007). Lipid-based nanoparticulate drug delivery systems. In D. Thassu, M. Deleers, & Y. Pathak (Eds.), Nanoparticulate drug delivery systems (1st ed.). New York: Informa Healthcare USA, Inc.Google Scholar
  147. 147.
    Puri, A., Loomis, K., Smith, B., et al. (2009). Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic. Critical Reviews in Therapeutic Drug Carrier Systems, 26(6), 523–580.CrossRefGoogle Scholar
  148. 148.
    Wissing, S. A., & Muller, R. H. (2003). The influence of solid lipid nanoparticles on skin hydration and viscoelasticity—in vivo study. European Journal of Pharmaceutics and Biopharmaceutics, 56(1), 67–72. doi: 10.1016/j.addr.2003.12.002.CrossRefGoogle Scholar
  149. 149.
    Wissing, S. A., Kayser, O., Muller, R. H. (2004). Solid lipid nanoparticles for parenteral drug delivery. Advanced Drug Delivery Reviews, 56(9), 1257–1272. doi: 10.1016/j.addr.2003.12.002.CrossRefGoogle Scholar
  150. 150.
    Heurtault, B., Saulnier, P., Pech, B., Proust, J. E., Benoit, J. P. (2002). A novel phase inversion-based process for the preparation of lipid nanocarriers. Pharmaceutical Research, 19(6), 875–880. doi: 10.1023/A:1016121319668.CrossRefGoogle Scholar
  151. 151.
    Charcosset, C., El-Harati, A., Fessi, H. (2005). Preparation of solid lipid nanoparticles using a membrane contactor. Journal of Controlled Release, 108(1), 112–120. doi: 10.1016/j.jconrel.2005.07.023.CrossRefGoogle Scholar
  152. 152.
    Schwarz, C., Mehnert, W., Lucks, J. S., Muller, R. H. (1994). Solid lipid nanoparticles (SLN) for controlled drug delivery: I. Production, characterization and sterilization. Journal of Controlled Release, 30, 83–96. doi: 10.1016/0168-3659(94)90047-7.CrossRefGoogle Scholar
  153. 153.
    Westesen, K., Bunjes, H., Koch, M. H. J. (1997). Physicochemical characterization of lipid nanoparticles and evaluation of their drug loading capacity and sustained release potential. Journal of Controlled Release, 48, 223–236. doi: 10.1016/S0168-3659(97)00046-1.CrossRefGoogle Scholar
  154. 154.
    Uner, M., & Yener, G. (2007). Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives. International Journal of Nanomedicine, 2(3), 289–300.Google Scholar
  155. 155.
    Liu, Z., Zhang, X., Wu, H., Li, J., Shu, L., Liu, R., Li, L., Li, N. (2011). Preparation and evaluation of solid lipid nanoparticles of baicalin for ocular drug delivery system in vitro and in vivo. Drug Development and Industrial Pharmacy, 37(4), 475–481. doi: 10.3109/03639045.2010.522193.CrossRefGoogle Scholar
  156. 156.
    Montenegro, L., Campisi, A., Sarpietro, M. G., et al. (2011). In vitro evaluation of idebenone-loaded solid lipid nanoparticles for drug delivery to the brain. Drug Dev Ind Pharm, 37(6), 737–746.CrossRefGoogle Scholar
  157. 157.
    Seyfoddin, A., Shaw, J., Al-Kassas, R. (2010). Solid lipid nanoparticles for ocular drug delivery. Drug Delivery, 17(7), 467–489. doi: 10.3109/10717544.2010.483257.CrossRefGoogle Scholar
  158. 158.
    Serpe, L., Canaparo, R., Daperno, M., Sostegni, R., Martinasso, G., Muntoni, E., Ippolito, L., Vivenza, N., Pera, A., Eandi, M., Gasco, M. R., Zara, G. P. (2010). Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model. European Journal of Pharmaceutical Sciences, 39(5), 428–436. doi: 10.1016/j.ejps.2010.01.013.CrossRefGoogle Scholar
  159. 159.
    Zhang, X. G., Miao, J., Dai, Y. Q., Du, Y. Z., Yuan, H., Hu, F. Q. (2008). Reversal activity of nanostructured lipid carriers loading cytotoxic drug in multi-drug resistant cancer cells. International Journal of Pharmaceutics, 361(1–2), 239–244. doi: 10.1016/j.ijpharm.2008.06.002.CrossRefGoogle Scholar
  160. 160.
    Teeranachaideekul, V., Muller, R. H., Junyaprasert, V. B. (2007). Encapsulation of ascorbylpalmitate in nanostructured lipid carriers (NLC)—effects of formulation parameters on physicochemical stability. International Journal of Pharmaceutics, 340(1–2), 198–206. doi: 10.1016/j.ijpharm.2007.03.022.CrossRefGoogle Scholar
  161. 161.
    Yuan, H., Wang, L. L., Du, Y. Z., You, J., Hu, F. Q., Zeng, S. (2007). Preparation and characteristics of nanostructured lipid carriers for control-releasing progesterone by melt-emulsification. Colloids and Surfaces. B, Biointerfaces, 60(2), 174–179. doi: 10.1016/j.colsurfb.2007.06.011.CrossRefGoogle Scholar
  162. 162.
    Jenning, V., Thunemann, A. F., Gohla, S. H. (2000). Characterization of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids. International Journal of Pharmaceutics, 1999, 167–177. doi: 10.1016/S0378-5173(00)00378-1.CrossRefGoogle Scholar
  163. 163.
    Jenning, V., Mader, K., Gohla, S. H. (2000). Solid lipid nanoparticles (SLN) based on binary mixtures of liquid and solid lipids: a1H-NMR study. International Journal of Pharmaceutics, 205, 15–21. doi: 10.1016/S0378-5173(00)00462-2.CrossRefGoogle Scholar
  164. 164.
    Joshi, M., & Patravale, M. (2006). Formulation and evaluation of nanostructured lipid carrier (NLC)-based gel of Valdecoxib. Drug Development and Industrial Pharmacy, 32(8), 911–918.CrossRefGoogle Scholar
  165. 165.
    Geßner, A., Olbrich, C., Schroder, W., Kayser, O., Muller, R. H. (2001). The role of plasma proteins in brain targeting: species dependent protein adsorption patterns on brain-specific lipid drug conjugate (LDC) nanoparticles. International Journal of Pharmaceutics, 214(1–2), 87–91. doi: 10.1016/S0378-5173(00)00639-6.CrossRefGoogle Scholar
  166. 166.
    Thevenot, J., TroutierAL, D. L., Delair, T., Ladaviere, C. (2007). Steric stabilization of lipid/polymer particle assemblies by poly(ethylene glycol)-lipids. Biomacromolecules, 8, 3651–3660. doi: 10.1021/bm700753q.CrossRefGoogle Scholar
  167. 167.
    Zhang, L., Chan, J. M., Gu, F. X., Rhee, J. W., Wang, A. Z., Radovic-Moreno, A. F., et al. (2008). Self-assembled lipid–polymer hybrid nanoparticles: a robust drug delivery platform. ACS Nano, 2, 1696–1702. doi: 10.1021/nn800275r.CrossRefGoogle Scholar
  168. 168.
    Chan, J. M., Zhang, L. F., Tong, R., Ghosh, D., Gao, W., et al. (2010). Spatio-temporal controlled delivery of nanoparticles to injured vasculature. Proceedings of the National Academy of Sciences, 107(5), 2213–2218. doi: 10.1073/pnas.0914585107.CrossRefGoogle Scholar
  169. 169.
    Yadav, K. S., & Sawant, K. K. (2010). Modified nanoprecipitation method for preparation of cytarabine-loaded PLGA nanoparticles. AAPS PharmSciTech, 11(3), 1456–1465. doi: 10.1208/s12249-010-9519-4.CrossRefGoogle Scholar
  170. 170.
    Fang, R. H., Aryal, S., Hu, C. M., Zhang, L. (2010). Quick synthesis of lipid-polymer hybrid nanoparticles with low polydispersity using a single-step sonication method. Langmuir, 26(22), 16958–16962. doi: 10.1021/la103576a.CrossRefGoogle Scholar
  171. 171.
    Ling, G., Zhang, P., Zhang, W., Sun, J., et al. (2010). Development of novel self-assembled DS-PLGA hybrid nanoparticles for improving oral bioavailability of vincristine sulfate by P-gp inhibition. Journal of Controlled Release, 148(2), 241–248. doi: 10.1016/j.jconrel.2010.08.010.CrossRefGoogle Scholar
  172. 172.
    Wang, A. Z., Gu, F., Zhang, L., Chan, J. M., Radovic-Moreno, A., Shaikh, M. R., Farokhzad, O. C. (2008). Biofunctionalized targeted nanoparticles for therapeutic applications. Expert Opinion on Biological Therapy, 8(8), 1063–1070. doi: 10.1517/14712598.8.8.1063.CrossRefGoogle Scholar
  173. 173.
    Hu, C. M. J., Kaushal, S., Cao, H. S. T., Aryal, S., Sartor, M., et al. (2010). Half-antibody functionalized lipid-polymer hybrid nanoparticles for targeted drug delivery to carcino embryonic antigen (CEA) presenting pancreatic cancer cells. Molecular Pharmaceutics, 7(3), 914–920. doi: 10.1021/mp900316a.CrossRefGoogle Scholar
  174. 174.
    Li, J., Ying-zi He, Y., Li, W., Shen, Y., Li, Y., Wang, Y. (2010). A novel polymer–lipid hybrid nanoparticle for efficient non-viral gene delivery. Acta Pharmacologica Sinica, 31, 509–514. doi: 10.1038/aps.2010.15.CrossRefGoogle Scholar
  175. 175.
    Sengupta, S., Eavarone, D., Capila, I., Zhao, G., Watson, N., Kiziltepe, T., Sasisekharan, R. (2005). Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system. Nature, 436(7050), 568–572. doi: 10.1038/nature03794.CrossRefGoogle Scholar
  176. 176.
    Yiu, T., Li, K., Li, P. J., Liu, B., Feng, S. S. (2010). Folic acid conjugated nanoparticles of mixed lipid monolayer shell and biodegradable polymer core for targeted delivery of Docetaxel. Biomaterials, 31, 330–338. doi: 10.1016/j.biomaterials.2009.09.036.CrossRefGoogle Scholar
  177. 177.
    Salvador-Morales, C., Zhang, L., Langer, R., Farokhzad, O. C. (2009). Immunocompatibility properties of lipid–polymer hybrid nanoparticles with heterogeneous surface functional groups. Biomaterials, 30, 2231–2240. doi: 10.1016/j.biomaterials.2009.01.005.CrossRefGoogle Scholar
  178. 178.
    Panyam, J., & Labhasetwar, V. (2003). Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Advanced Drug Delivery Reviews, 55(3), 329–347. doi: 10.1016/S0169-409X(02)00228-4.CrossRefGoogle Scholar
  179. 179.
    Desai, M. P., Labhasetwar, V., Walter, E., Levy, R. J., Amidon, G. L. (1997). The mechanism of uptake of biodegradable microparticles in Caco-2 cells is size dependent. Pharmaceutical Research, 14(11), 1568–1573. doi: 10.1023/A:1012126301290.CrossRefGoogle Scholar
  180. 180.
    Desai, M. P., Labhasetwar, V., Amidon, G. L., Levy, R. J. (1996). Gastrointestinal uptake of biodegradable microparticles: effect of particle size. Pharmaceutical Research, 13(12), 1838–1845. doi: 10.1023/A:1016085108889.CrossRefGoogle Scholar
  181. 181.
    Zauner, W., Farrow, N. A., Haines, A. M. (2001). In vitro uptake of polystyrene microspheres: effect of particle size, cell line and cell density. Journal of Controlled Release, 71(1), 39–51. doi: 10.1016/S0168-3659(00)00358-8.CrossRefGoogle Scholar
  182. 182.
    Redhead, H. M., Davis, S. S., Illum, L. (2001). Drug delivery in poly(lactide-co-glycolide) nanoparticles surface modified with poloxamer 407 and poloxamine 908: in vitro characterisation and in vivo evaluation. Journal of Controlled Release, 70(3), 353–363. doi: 10.1023/A:1022604120952.CrossRefGoogle Scholar
  183. 183.
    Dwibhashyam, V. S. N. M., & Nagappa, A. N. (2008). Strategies for enhanced drug delivery to the central nervous system. Indian Journal of Pharmaceutical Sciences, 70(2), 145–153. doi: 10.4103/0250-474X.41446.CrossRefGoogle Scholar
  184. 184.
    Kreuter, J., Ramge, P., Petrov, V., Hamm, S., Gelperina, S. E., Engelhardt, B., Alyautdin, R., von Briesen, H., Begley, D. J. (2003). Direct evidence that polysorbate-80-coated poly(butylcyanoacrylate) nanoparticles deliver drugs to the CNS via specific mechanisms requiring prior binding of drug to the nanoparticles. Pharmaceutical Research, 20(3), 409–416. doi: 10.1023/A:1022604120952.CrossRefGoogle Scholar
  185. 185.
    Jores, K., Mehnert, W., Mader, K. (2003). Physicochemical investigations on solid–lipid nanoparticles and on oil loaded solid–lipid nanoparticles: a nuclear magnetic resonance and electron spin resonance study. Pharmaceutical Research, 20, 1274–1283. doi: 10.1023/A:1025065418309.CrossRefGoogle Scholar
  186. 186.
    Maestrell, F., Mura, P., Alonso, M. J. (2004). Formulation and characterization of triclosan sub-micronemulsions and nanocapsules. Journal of Microencapsulation, 21(8), 857–864. doi: 10.1080/02652040400015411.CrossRefGoogle Scholar
  187. 187.
    Lochmann, D., Vogel, V., Weyermann, J., et al. (2004). Physicochemical characterization of protamine-phosphorothioate nanoparticles. Journal of Microencapsulation, 21(6), 625–641. doi: 10.1080/02652040400000504.CrossRefGoogle Scholar
  188. 188.
    Geze, A., Putaux, J. L., Choisnard, L., Jehan, P., Wouessidjewe, D. (2004). Long term shelf stability of amphiphilic B-cyclodextrin nanospheres suspensions monitored by dynamic light scattering and cryo-transmission electron microscopy. Journal of Microencapsulation, 21, 607–613. doi: 10.1080/02652040400008457%20.CrossRefGoogle Scholar
  189. 189.
    Wang, X., Dai, J., Chen, Z., et al. (2004). Bioavailability and pharmacokinetics of cyclosporine A loaded pH-sensitive nanoparticles for oral administration. Journal of Controlled Release, 97, 421–429. doi: 10.1016/j.jconrel.2004.03.003.Google Scholar
  190. 190.
    Muniyappan, S. V. T., Karatgi, P., Prabu, R., Pillai, R. (2008). Production and in vitro characterization of solid dosage form incorporating drug nanoparticles. Drug Development and Industrial Pharmacy, 34(11), 1209–1218. doi: 10.1080/03639040802005024.CrossRefGoogle Scholar
  191. 191.
    Yoo, H. S., & Park, T. G. (2004). Biodegradable nanoparticles containing protein–fatty acid complexes for oral delivery of salmon calcitonin. Journal of Pharmaceutical Sciences, 93, 488–495. doi: 10.1002/jps.10573.CrossRefGoogle Scholar
  192. 192.
    Alphandary, H. P., Aboubaker, M., Jaillard, D., Couvreur, P., Vauthier, C. (2003). Visualization of insulin loaded nanocapsules: in vitro and in vivo studies after oral administration to rats. Pharmaceutical Research, 20(7), 1071–1084. doi: 10.1023/A:1024470508758.CrossRefGoogle Scholar
  193. 193.
    Alexis, F., Pridgen, E., Molnar, L. K., Farokhzad, O. C. (2008). Factors affecting the clearance and biodistribution of polymeric nanoparticles. Molecular Pharmaceutics, 5(4), 505–515. doi: 10.1021/mp800051m.CrossRefGoogle Scholar
  194. 194.
    Bershteyn, A., Chaparro, J., Yau, R., Kim, M., Reinherz, E., et al. (2008). Polymer-supported lipid shells, onions, and flowers. Soft Matter, 4(9), 1787–1791. doi: 10.1039/b804933e.CrossRefGoogle Scholar
  195. 195.
    Govender, T., Stolnik, S., Garnett, M. C., Illum, L., Davis, S. S. (1999). PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. Journal of Controlled Release, 57(2), 171–185. doi: 10.1016/S0168-3659(98)00116-3.CrossRefGoogle Scholar
  196. 196.
    Govender, T., Riley, T., Ehtezazi, T., Garnett, M. C., Stolnik, S., Illum, L., Davis, S. S. (2000). Defining the drug incorporation properties of PLA–PEG nanoparticles. International Journal of Pharmaceutics, 199(1), 95–110. doi: 10.1016/S0378-5173(00)00375-6.CrossRefGoogle Scholar
  197. 197.
    Chen, Y., McCulloch, R. K., Gray, B. N. (1994). Synthesis of albumin-dextran sulfate microspheres possessing favourable loading and release characteristics for the anti-cancer doxorubicin. Journal of Controlled Release, 31(1), 49–54. doi: 10.1016/0168-3659(94)90250-X.CrossRefGoogle Scholar
  198. 198.
    Peracchia, M., Gref, R., Minamitake, Y., Domb, A., Lotan, N., Langer, R. (1997). PEG-coated nanospheres from amphiphillic diblock and multiblock copolymers: investigation of their drug encapsulation and release characteristics. Journal of Controlled Release, 46(3), 223–231. doi: 10.1016/S0168-3659(96)01597-0.CrossRefGoogle Scholar
  199. 199.
    Aryal, S., Hu, C. M. J., Zhang, L. F. (2010). Polymer–cisplatin conjugate nanoparticles for acid-responsive drug delivery. ACS Nano, 4, 251–258. doi: 10.1021/nn9014032.CrossRefGoogle Scholar
  200. 200.
    Kundu, J., Chung, Y. I., Kim, Y. H., Taeb, G., Kundu, S. C. (2010). Silk fibroin nanoparticles for cellular uptake and control release. International Journal of Pharmaceutics, 388(1–2), 242–250. doi: 10.1016/j.ijpharm.2009.12.052.CrossRefGoogle Scholar
  201. 201.
    Kaul, G., & Amiji, M. (2002). Long-circulating poly(ethylene glycol)-modified gelatin nanoparticles for intracellular delivery. Pharmaceutical Research, 19(7), 1061–1067. doi: 10.1023/A:1016486910719.CrossRefGoogle Scholar
  202. 202.
    Nam, H. Y., Kwon, S. M., Chung, H., et al. (2009). Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles. Journal of Controlled Release, 135(3), 259–267. doi: 10.1016/j.jconrel.2009.01.018.CrossRefGoogle Scholar
  203. 203.
    Jeong, Y. I., Jin, S. G., Kim, I. Y., et al. (2010). Doxorubicin-incorporated nanoparticles composed of poly(ethylene glycol)-grafted carboxymethyl chitosan and antitumor activity against glioma cells in vitro. Colloids and Surfaces B, 79(1), 149–155. doi: 10.1016/j.colsurfb.2010.03.037.CrossRefGoogle Scholar
  204. 204.
    Verdun, C., Brasseur, F., Vranckx, H., Couvreur, P., Roland, M. (1990). Tissue distribution of doxorubicin associated with polyhexylcyanoacrylate nanoparticles. Cancer Chemotherapy and Pharmacology, 26(1), 13–18. doi: 10.1007/BF0294028.CrossRefGoogle Scholar
  205. 205.
    Storm, G., Belliot, S., Daemen, T., Lasic, D. (1995). Surface modification of nanoparticles to oppose uptake by the mononuclear phagocyte system. Advanced Drug Delivery Reviews, 17, 31–48. doi: 10.1016/0169-409X(95)00039-A.CrossRefGoogle Scholar
  206. 206.
    Jeon, S. I., Lee, J. H., Andrade, J. D., De Gennes, P. G. (1991). Protein-surface interactions in the presence of polyethylene oxide: I. Simplified theory. Journal of Colloid and Interface Science, 142, 149–158. doi: 10.1016/0021-9797(91)90043-8.CrossRefGoogle Scholar
  207. 207.
    Stella, B., Arpicco, S., Peracchia, M., Desmaele, D., Hoebeke, J., Renoir, M., Angelo, J., Cattel, L., Couvreur, P. (2000). Design of folic acid-conjugated nanoparticles for drug targeting. Journal of Pharmaceutical Sciences, 89(11), 1452–1464. doi: 10.1002/1520-6017(200011)89:11<1452::AID-JPS8>3.0.CO;2-P.CrossRefGoogle Scholar
  208. 208.
    Larsen, A. K., Escargueil, A. E., Skladanowski, A. (2000). Resistance mechanisms associated with altered intracellular distribution of anticancer agents. Pharmacology and Therapeutics, 85(3), 217–229. doi: 10.1016/S0163-7258(99)00073-X.CrossRefGoogle Scholar
  209. 209.
    Bennis, S., Chapey, C., Couvreur, P., Robert, J. (1994). Enhanced cytotoxicity of doxorubicin encapsulated in polyisohexylcyanoacrylate nanospheres against multidrug-resistant tumour cells in culture. European Journal of Cancer, 30A(1), 89–93.CrossRefGoogle Scholar
  210. 210.
    Damge, C., Michel, C., Aprahamian, M., Couvreur, P., Devissaguet, J. P. (1990). Nanocapsules as carriers for oral peptide delivery. Journal of Controlled Release, 13, 233–239. doi: 10.1016/0168-3659(90)90013-J.CrossRefGoogle Scholar
  211. 211.
    Brandtzaeg, P., Berstad, A., Farstad, I., Haraldsen, G., Helgeland, L., Jahnsen, F., Johansen, F., Natvig, I., Nilsen, E., Rugtveit, J. (1997). Mucosal immunity—a major adaptive defense mechanism. Behring Institute Mitteilungen, 98(1), 1–23.Google Scholar
  212. 212.
    Moghimi, S. M., Hunter, A. C., Murray, J. C. (2001). Long-circulating and target-specific nanoparticles: theory to practice. Pharmacological Reviews, 53, 283–318. doi: 0031-6997/01/5302-283-318$3.00.Google Scholar
  213. 213.
    Bromberg, L. E., Ron, E. S. (1998). Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery. Advanced Drug Delivery Reviews, 31(3), 197–221. doi: 10.1016/S0169-409X(97)00121-X.CrossRefGoogle Scholar
  214. 214.
    Haltner, E., Easson, J., Lehr, C. (1997). Lectins and bacterial invasion factors for controlling endo- and transcytosis of bioadhesive drug carrier systems. European Journal of Pharmaceutics and Biopharmaceutics, 44, 3–13.CrossRefGoogle Scholar
  215. 215.
    Hussain, N., Jani, P. U., Florence, A. T. (1997). Enhanced oral uptake of tomato lectin-conjugated nanoparticles in the rat. Pharmaceutical Research, 14(5), 613–618. doi: 10.1023/A:1012153011884.CrossRefGoogle Scholar
  216. 216.
    Russell-Jones, G. J., Arthur, L., Walker, H. (1999). Vitamin B12-mediated transport of nanoparticles across Caco-2 cells. International Journal of Pharmaceutics, 179(2), 247–255. doi: 10.1016/S0378-5173(98)00394-9.CrossRefGoogle Scholar
  217. 217.
    Veiseh, O., Sun, C., Fang, C., Bhattarai, N., Gunn, J., Kievit, F., Du, K., Pullar, B., Lee, D., Ellenbogen, R. G., Olson, J., Zhang, M. (2009). Specific targeting of brain tumors with an optical/magnetic resonance imaging nanoprobe across the blood–brain barrier. Cancer Research, 69, 6200–6207.CrossRefGoogle Scholar
  218. 218.
    Patel, M. M., Goyal, B. R., Bhadada, S. V., Bhatt, J. S., Amin, A. F. (2009). Getting into the brain: approaches to enhance brain drug delivery. CNS Drugs, 23(1), 35–58. doi: 10.2165/0023210-200923010-00003.CrossRefGoogle Scholar
  219. 219.
    Lockman, P. R., Koziara, J. M., Mumper, R. J., et al. (2004). Nanoparticle surface charges alter blood–brain barrier integrity and permeability. Journal of Drug Targeting, 12(9–10), 635–641. doi: 10.1080/10611860400015936.CrossRefGoogle Scholar
  220. 220.
    Costantino, L., Gandolfi, F., Tosi, G., Rivasi, F., Vandelli, M. A., Forni, F. (2005). Peptide-derivatized biodegradable nanoparticles able to cross the blood–brain barrier. Journal of Controlled Release, 108(1), 84–96. doi: 10.1016/j.jconrel.2005.07.013.CrossRefGoogle Scholar
  221. 221.
    Tahara, K., Miyazaki, Y., Kawashima, Y., Kreuter, J., Yamamoto, H. (2011). Brain targeting with surface-modified poly(d, l-lactic-co-glycolic acid) nanoparticles delivered via carotid artery administration. European Journal of Pharmaceutics and Biopharmaceutics, 77(1), 84–88. doi: 10.1016/j.ejpb.2010.11.002.CrossRefGoogle Scholar
  222. 222.
    Cho, K., Wang, X., Nie, S., et al. (2008). Therapeutic nanoparticles for drug delivery in cancer. Clinicalo Cancer Research, 14(5), 1310–1316. doi: 10.1158/1078-0432.CCR-07-1441.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Sandeep Kumar
    • 1
    Email author
  • Neeraj Dilbaghi
    • 1
  • Ruma Saharan
    • 1
  • Gaurav Bhanjana
    • 1
  1. 1.Nanomaterials Synthesis & Characterization Laboratory, Department of Bio & Nano TechnologyGuru Jambheshwar University of Science and TechnologyHisarIndia

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