The AAPS Journal

, Volume 14, Issue 4, pp 688–702 | Cite as

Engineered Nanoparticulate Drug Delivery Systems: The Next Frontier for Oral Administration?

  • Roudayna DiabEmail author
  • Chiraz Jaafar-Maalej
  • Hatem Fessi
  • Philippe Maincent
Review Article Theme: Develop Enabling Technologies for Delivering Poorly Water Soluble Drugs: Current Status and Future Perspectives


For the past few decades, there has been a considerable research interest in the area of oral drug delivery using nanoparticle (NP) delivery systems as carriers. Oral NPs have been used as a physical approach to improve the solubility and the stability of active pharmaceutical ingredients (APIs) in the gastrointestinal juices, to enhance the intestinal permeability of drugs, to sustain and to control the release of encapsulated APIs allowing the dosing frequency to be reduced, and finally, to achieve both local and systemic drug targeting. Numerous materials have been used in the formulation of oral NPs leading to different nanoparticulate platforms. In this paper, we review various aspects of the formulation and the characterization of polymeric, lipid, and inorganic NPs. Special attention will be dedicated to their performance in the oral delivery of drug molecules and therapeutic genes.


biodegradable nanoparticles natural oral polymer 


  1. 1.
    Pang KS. Modeling of intestinal drug absorption: roles of transporters and metabolic enzymes (for the Gillette Review Series). Drug Metab Dispos. 2003;31:1507–19.PubMedGoogle Scholar
  2. 2.
    Panchagnula R, Thomas NS. Biopharmaceutics and pharmacokinetics in drug research. Int J Pharm. 2000;201:131–50.PubMedGoogle Scholar
  3. 3.
    Marre F, Sanderink GJ, de Sousa G, Gaillard C, Martinet M, Rahmani R. Hepatic biotransformation of docetaxel (Taxotere) in vitro: involvement of the CYP3A subfamily in humans. Cancer Res. 1996;56:1296–302.PubMedGoogle Scholar
  4. 4.
    Li F, Maag H, Alfredson T. Prodrugs of nucleoside analogues for improved oral absorption and tissue targeting. J Pharm Sci. 2008;97:1109–34.PubMedGoogle Scholar
  5. 5.
    Saini SD, Schoenfeld P, Kaulback K, Dubinsky MC. Effect of medication dosing frequency on adherence in chronic diseases. Am J Manag Care. 2009;15:e22–33.PubMedGoogle Scholar
  6. 6.
    Bowman K, Leong KW. Chitosan nanoparticles for oral drug and gene delivery. Int J Nanomedicine. 2006;1:117–28.PubMedGoogle Scholar
  7. 7.
    Sosnik A, Carcaboso A, Chiappetta D. Polymeric nanocarriers: new endeavors for the optimization of the technological aspects of drugs. Recent Patents Biomed Eng. 2008;1:43–59.Google Scholar
  8. 8.
    Florence AT. Issues in oral nanoparticle drug carrier uptake and targeting. J Drug Target. 2004;12:65–70.PubMedGoogle Scholar
  9. 9.
    Gelperina S, Kisich K, Iseman MD, Heifets L. The potential advantages of nanoparticle drug delivery systems in chemotherapy of tuberculosis. Am J Respir Crit Care Med. 2005;172:1487–90.PubMedGoogle Scholar
  10. 10.
    Brayden DJ, Baird AW. Apical membrane receptors on intestinal M cells: potential targets for vaccine delivery. Adv Drug Deliv Rev. 2004;56:721–6.PubMedGoogle Scholar
  11. 11.
    des Rieux A, Fievez V, Garinot M, Schneider Y, Préat V. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release. 2006;116:1–27.PubMedGoogle Scholar
  12. 12.
    Lamprecht A. IBD: selective nanoparticle adhesion can enhance colitis therapy. Nat Rev Gastroenterol Hepatol. 2010;7:311–2.PubMedGoogle Scholar
  13. 13.
    Park JH, Saravanakumar G, Kim K, Kwon IC. Targeted delivery of low molecular drugs using chitosan and its derivatives. Adv Drug Deliv Rev. 2010;62:28–41.PubMedGoogle Scholar
  14. 14.
    Löbenberg R, Araujo I, Kreuter J. Body distribution of azidothymidine bound to nanoparticles after oral administration. Eur J Pharm Biopharm. 1997;44:127–32.Google Scholar
  15. 15.
    Sharma A, Sharma S, Khuller GK. Lectin-functionalized poly (lactide-co-glycolide) nanoparticles as oral/aerosolized antitubercular drug carriers for treatment of tuberculosis. J Antimicrob Chemother. 2004;54:761–6.PubMedGoogle Scholar
  16. 16.
    Pandey R, Khuller GK. Oral nanoparticle-based antituberculosis drug delivery to the brain in an experimental model. J Antimicrob Chemother. 2006;57:1146–52.PubMedGoogle Scholar
  17. 17.
    Plapied L, Vandermeulen G, Vroman B, Préat V, des Rieux A. Bioadhesive nanoparticles of fungal chitosan for oral DNA delivery. Int J Pharm. 2010;398:210–8.PubMedGoogle Scholar
  18. 18.
    Laurienzo P. Marine polysaccharides in pharmaceutical applications: an overview. Mar Drugs. 2010;8:2435–65.PubMedGoogle Scholar
  19. 19.
    Illum L, Farraj NF, Davis SS. Chitosan as a novel nasal delivery system for peptide drugs. Pharm Res. 1994;11:1186–9.PubMedGoogle Scholar
  20. 20.
    Schipper NG, Vârum KM, Stenberg P, Ocklind G, Lennernäs H, Artursson P. Chitosans as absorption enhancers of poorly absorbable drugs. 3: Influence of mucus on absorption enhancement. Eur J Pharm Sci. 1999;8:335–43.PubMedGoogle Scholar
  21. 21.
    Schipper NG, Olsson S, Hoogstraate JA, deBoer AG, Vårum KM, Artursson P. Chitosans as absorption enhancers for poorly absorbable drugs 2: mechanism of absorption enhancement. Pharm Res. 1997;14:923–9.PubMedGoogle Scholar
  22. 22.
    Schipper NG, Vårum KM, Artursson P. Chitosans as absorption enhancers for poorly absorbable drugs. 1: Influence of molecular weight and degree of acetylation on drug transport across human intestinal epithelial (Caco-2) cells. Pharm Res. 1996;13:1686–92.PubMedGoogle Scholar
  23. 23.
    Sarmento B, Ribeiro A, Veiga F, Sampaio P, Neufeld R, Ferreira D. Alginate/chitosan nanoparticles are effective for oral insulin delivery. Pharm Res. 2007;24:2198–206.PubMedGoogle Scholar
  24. 24.
    Lu E, Franzblau S, Onyuksel H, Popescu C. Preparation of aminoglycoside-loaded chitosan nanoparticles using dextran sulphate as a counterion. J Microencapsul. 2009;26:346–54.PubMedGoogle Scholar
  25. 25.
    Chew JL, Wolfowicz CB, Mao H, Leong KW, Chua KY. Chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen, Der p 1 for oral vaccination in mice. Vaccine. 2003;21:2720–9.PubMedGoogle Scholar
  26. 26.
    Borges O, Tavares J, de Sousa A, Borchard G, Junginger HE, Cordeiro-da-Silva A. Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate-coated chitosan nanoparticles. Eur J Pharm Sci. 2007;32:278–90.PubMedGoogle Scholar
  27. 27.
    Zhao K, Shi X, Zhao Y, Wei H, Sun Q, Huang T, et al. Preparation and immunological effectiveness of a swine influenza DNA vaccine encapsulated in chitosan nanoparticles. Vaccine. 2011;29:8549–56.PubMedGoogle Scholar
  28. 28.
    Mao S, Sun W, Kissel T. Chitosan-based formulations for delivery of DNA and siRNA. Adv Drug Deliv Rev. 2010;62:12–27.PubMedGoogle Scholar
  29. 29.
    Ohya Y, Shiratania M, Kobayashia H, Ouchia T. Release behavior of 5-fluorouracil from chitosan-gel nanospheres immobilizing 5-fluorouracil coated with polysaccharides and their cell specific cytotoxicity. J Macromolecular Sci Pure Appl Chem. 1994; doi: 10.1080/10601329409349743
  30. 30.
    Zhang S, Kawakami K. One-step preparation of chitosan solid nanoparticles by electrospray deposition. Int J Pharm. 2010;397:211–7.Google Scholar
  31. 31.
    Jain A, Jain SK. In vitro and cell uptake studies for targeting of ligand anchored nanoparticles for colon tumors. Eur J Pharm Sci. 2008;35:404–16.PubMedGoogle Scholar
  32. 32.
    Bayat A, Dorkoosh FA, Dehpour AR, Moezi L, Larijani B, Junginger HE, et al. Nanoparticles of quaternized chitosan derivatives as a carrier for colon delivery of insulin: ex vivo and in vivo studies. Int J Pharm. 2008;356:259–66.PubMedGoogle Scholar
  33. 33.
    Zhang H, Neau SH. In vitro degradation of chitosan by bacterial enzymes from rat cecal and colonic contents. Biomaterials. 2002;23:2761–6.PubMedGoogle Scholar
  34. 34.
    Jain A, Jain SK, Ganesh N, Barve J, Beg AM. Design and development of ligand-appended polysaccharidic nanoparticles for the delivery of oxaliplatin in colorectal cancer. Nanomedicine. 2010;6:179–90.PubMedGoogle Scholar
  35. 35.
    Atyabi F, Talaie F, Dinarvand R. Thiolated chitosan nanoparticles as an oral delivery system for amikacin: in vitro and ex vivo evaluations. J Nanosci Nanotechnol. 2009;9:4593–603.PubMedGoogle Scholar
  36. 36.
    Malhotra M, Lane C, Tomaro-Duchesneau C, Saha S, Prakash S. A novel method for synthesizing PEGylated chitosan nanoparticles: strategy, preparation, and in vitro analysis. Int J Nanomedicine. 2011;6:485–94.PubMedGoogle Scholar
  37. 37.
    Wang Q, Jamal S, Detamore MS, Berkland C. PLGA-chitosan/PLGA-alginate nanoparticle blends as biodegradable colloidal gels for seeding human umbilical cord mesenchymal stem cells. J Biomed Mater Res A. 2011;96:520–7.PubMedGoogle Scholar
  38. 38.
    Smidsrød O, Skjåk-Braek G. Alginate as immobilization matrix for cells. Trends Biotechnol. 1990;8:71–8.PubMedGoogle Scholar
  39. 39.
    Sonavane GS, Devarajan PV. Preparation of alginate nanoparticles using Eudragit E100 as a new complexing agent: development, in-vitro, and in-vivo evaluation. J Biomed Nanotech. 2007;3:160–9.Google Scholar
  40. 40.
    Rajaonarivony M, Vauthier C, Couarraze G, Puisieux F, Couvreur P. Development of a new drug carrier made from alginate. J Pharm Sci. 1993;82:912–7.PubMedGoogle Scholar
  41. 41.
    Ahmad Z, Pandey R, Sharma S, Khuller GK. Alginate nanoparticles as antituberculosis drug carriers: formulation development, pharmacokinetics and therapeutic potential. Indian J Chest Dis Allied Sci. 2006;48:171–6.PubMedGoogle Scholar
  42. 42.
    Arangoa MA, Campanero MA, Renedo MJ, Ponchel G, Irache JM. Gliadin nanoparticles as carriers for the oral administration of lipophilic drugs. Relationships between bioadhesion and pharmacokinetics. Pharm Res. 2001;18:1521–7.PubMedGoogle Scholar
  43. 43.
    Patil GV. Biopolymer albumin for diagnosis and in drug delivery. Drug Dev Res. 2003;58:219–47.Google Scholar
  44. 44.
    Toshio Y, Mitsuru H, Shozo M, Hitoshi S. Specific delivery of mitomycin C to the liver, spleen, and lung: nano- and microspherical carriers of gelatin. Int J Pharm. 1981;8:131–41.Google Scholar
  45. 45.
    Langer K, Balthasar S, Vogel V, Dinauer N, von Briesen H, Schubert D. Optimization of the preparation process for human serum albumin (HSA) nanoparticles. Int J Pharm. 2003;257:169–80.PubMedGoogle Scholar
  46. 46.
    Lin W, Coombes AG, Davies MC, Davis SS, Illum L. Preparation of sub-100 nm human serum albumin nanospheres using a pH-coacervation method. J Drug Target. 1993;1:237–43.PubMedGoogle Scholar
  47. 47.
    Kumar PV, Jain NK. Suppression of agglomeration of ciprofloxacin-loaded human serum albumin nanoparticles. AAPS Pharm Sci Technol. 2007;8:17.Google Scholar
  48. 48.
    Umamaheshwari RB, Jain NK. Receptor mediated targeting of lectin conjugated gliadin nanoparticles in the treatment of Helicobacter pylori. J Drug Target. 2003;11:415–24.PubMedGoogle Scholar
  49. 49.
    Bhavsar MD, Amiji MM. Gastrointestinal distribution and in vivo gene transfection studies with nanoparticles-in-microsphere oral system (NiMOS). J Control Release. 2007;119:339–48.PubMedGoogle Scholar
  50. 50.
    Roy S, Pal K, Anis A, Pramanik K, Prabhakar B. Polymers in mucoadhesive drug delivery system: a brief note. Des Monomers Polym. 2009;12:483–95.Google Scholar
  51. 51.
    Wang W, Chen H, Liang W. Study on polymethacrylate nanoparticles as delivery system of antisense oligodeoxynucleotides. Yao Xue Xue Bao. 2003;38:298–301.PubMedGoogle Scholar
  52. 52.
    Gargouri M, Sapin A, Bouli S, Becuwe P, Merlin JL, Maincent P. Optimization of a new non-viral vector for transfection: Eudragit nanoparticles for the delivery of a DNA plasmid. Technol Cancer Res Treat. 2009;8:433–44.PubMedGoogle Scholar
  53. 53.
    Jiao YY, Ubrich N, Marchand-Arvier M, Vigneron C, Hoffman M, Maincent P. Preparation and in vitro evaluation of heparin-loaded polymeric nanoparticles. Drug Deliv. 2001;8:135–41.PubMedGoogle Scholar
  54. 54.
    Jiao Y, Ubrich N, Marchand-Arvier M, Vigneron C, Hoffman M, Lecompte T, et al. In vitro and in vivo evaluation of oral heparin-loaded polymeric nanoparticles in rabbits. Circulation. 2002;105:230–5.PubMedGoogle Scholar
  55. 55.
    Attivi D, Wehrle P, Ubrich N, Damge C, Hoffman M, Maincent P. Formulation of insulin-loaded polymeric nanoparticles using response surface methodology. Drug Dev Ind Pharm. 2005;31:179–89.PubMedGoogle Scholar
  56. 56.
    Tamizhrasi S, Shukla A, Shivkumar T, Rathi V, Rathi JC. Formulation and evaluation of lamivudine loaded polymethacrylic acid nanoparticles. Int J Pharm Technol Res. 2009;1:411–5.Google Scholar
  57. 57.
    Leroux JC, Cozens R, Roesel JL, Galli B, Kubel F, Doelker E, et al. Pharmacokinetics of a novel HIV-1 protease inhibitor incorporated into biodegradable or enteric nanoparticles following intravenous and oral administration to mice. J Pharm Sci. 1995;84:1387–91.PubMedGoogle Scholar
  58. 58.
    Jelvehgari M, Zakeri-Milani P, Siahi-Shadbad MR, Loveymi BD, Nokhodchi A, Azari Z, et al. Development of pH-sensitive insulin nanoparticles using Eudragit L100-55 and chitosan with different molecular weights. AAPS Pharm Sci Technol. 2010;11:1237–42.Google Scholar
  59. 59.
    Gupta MK, Mishra B, Prakash D, Rai SK. Nanoparticulate drug delivery system of cyclosporine. Int J Pharm Pharm Sci. 2009;1:81–92.Google Scholar
  60. 60.
    Eerikäinen H, Kauppinen EI. Preparation of polymeric nanoparticles containing corticosteroid by a novel aerosol flow reactor method. Int J Pharm. 2003;263:69–83.PubMedGoogle Scholar
  61. 61.
    Xiong X, Tam K. Hydrolytic degradation of pluronic F127/poly(lactic acid) block copolymer nanoparticles. Macromolecules. 2004;37:3425–30.Google Scholar
  62. 62.
    Dash TK, Konkimalla VB. Poly-є-caprolactone based formulations for drug delivery and tissue engineering: a review. J Control Release. 2011. doi: 10.1016/j.jconrel.2011.09.064.
  63. 63.
    Chawla JS, Amiji MM. Biodegradable poly(epsilon -caprolactone) nanoparticles for tumor-targeted delivery of tamoxifen. Int J Pharm. 2002;249:127–38.PubMedGoogle Scholar
  64. 64.
    Varela MC, Guzmán M, Molpeceres J, del Rosario Aberturas M, Rodríguez-Puyol D, Rodríguez-Puyol M. Cyclosporine-loaded polycaprolactone nanoparticles: immunosuppression and nephrotoxicity in rats. Eur J Pharm Sci. 2001;12:471–8.PubMedGoogle Scholar
  65. 65.
    Xiong XY, Li YP, Li ZL, Zhou CL, Tam KC, Liu ZY, et al. Vesicles from pluronic/poly(lactic acid) block copolymers as new carriers for oral insulin delivery. J Control Release. 2007;120:11–7.PubMedGoogle Scholar
  66. 66.
    Cegnar M, Kos J, Kristl J. Cystatin incorporated in poly(lactide-co-glycolide) nanoparticles: development and fundamental studies on preservation of its activity. Eur J Pharm Sci. 2004;22:357–64.PubMedGoogle Scholar
  67. 67.
    Vila A, Sánchez A, Tobío M, Calvo P, Alonso MJ. Design of biodegradable particles for protein delivery. J Control Release. 2002;78:15–24.PubMedGoogle Scholar
  68. 68.
    Garinot M, Fiévez V, Pourcelle V, Stoffelbach F, des Rieux A, Plapied L, et al. PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination. J Control Release. 2007;120:195–204.PubMedGoogle Scholar
  69. 69.
    Jesorka A, Orwar O. Liposomes: technologies and analytical applications. Annu Rev Anal Chem (Palo Alto Calif). 2008;1:801–32.Google Scholar
  70. 70.
    Villasmil-Sánchez S, Drhimeur W, Ospino SCS, Rabasco Alvarez AM, González-Rodríguez ML. Positively and negatively charged liposomes as carriers for transdermal delivery of sumatriptan: in vitro characterization. Drug Dev Ind Pharm. 2010;36:666–75.PubMedGoogle Scholar
  71. 71.
    Dial EJ, Rooijakkers SHM, Darling RL, Romero JJ, Lichtenberger LM. Role of phosphatidylcholine saturation in preventing bile salt toxicity to gastrointestinal epithelia and membranes. J Gastroenterol Hepatol. 2008;23:430–6.PubMedGoogle Scholar
  72. 72.
    Porter CJH, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007;6:231–48.PubMedGoogle Scholar
  73. 73.
    Sun J, Deng Y, Wang S, Cao J, Gao X, Dong X. Liposomes incorporating sodium deoxycholate for hexamethylmelamine (HMM) oral delivery: development, characterization, and in vivo evaluation. Drug Deliv. 2010;17:164–70.PubMedGoogle Scholar
  74. 74.
    Ling SSN, Yuen KH, Magosso E, Barker SA. Oral bioavailability enhancement of a hydrophilic drug delivered via folic acid-coupled liposomes in rats. J Pharm Pharmacol. 2009;61:445–9.PubMedGoogle Scholar
  75. 75.
    Müller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery—a review of the state of the art. Eur J Pharm Biopharm. 2000;50:161–77.PubMedGoogle Scholar
  76. 76.
    Souto E, Müller R. Lipid nanoparticles (SLN and NLC) for drug delivery. In: Domb AJ, Tabata Y, Kumar MNVR, Farber S, editors. Nanoparticles for pharmaceutical applications. California: American Scientific Publishers; 2007. p. 103–22.Google Scholar
  77. 77.
    Tomoyasu Y, Yasuda T, et al. Liposome-encapsulated midazolam for oral administration. J Liposome Res. 2011;21:166–72.PubMedGoogle Scholar
  78. 78.
    Cao J, Sun J, et al. N-trimethyl chitosan-coated multivesicular liposomes for oxymatrine oral delivery. Drug Dev Ind Pharm. 2009;35:1339–47.PubMedGoogle Scholar
  79. 79.
    Sun W, Zhang N, et al. Preparation and evaluation of N(3)-O-toluyl-fluorouracil-loaded liposomes. Int J Pharm. 2008;353:243–50.PubMedGoogle Scholar
  80. 80.
    Uner M, Yener G. Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives. Int J Nanomedicine. 2007;2:289–300.PubMedGoogle Scholar
  81. 81.
    Garcia-Fuentes M, Torres D, Alonso M. Design of lipid nanoparticles for the oral delivery of hydrophilic macromolecules. Colloid Surf B. 2003;27:159–68.Google Scholar
  82. 82.
    Olbrich C, Müller RH. Enzymatic degradation of SLN-effect of surfactant and surfactant mixtures. Int J Pharm. 1999;180:31–9.PubMedGoogle Scholar
  83. 83.
    Barauskas J, Johnsson M, Tiberg F. Self-assembled lipid superstructures: beyond vesicles and liposomes. Nano Lett. 2005;5:1615–9.PubMedGoogle Scholar
  84. 84.
    Lai J, Chen J, Lu Y, Sun J, Hu F, Yin Z, et al. Glyceryl monooleate/poloxamer 407 cubic nanoparticles as oral drug delivery systems: I. In vitro evaluation and enhanced oral bioavailability of the poorly water-soluble drug simvastatin. AAPS Pharm Sci Technol. 2009;10:960–6.Google Scholar
  85. 85.
    Lai J, Lu Y, Yin Z, Hu F, Wu W. Pharmacokinetics and enhanced oral bioavailability in beagle dogs of cyclosporine A encapsulated in glyceryl monooleate/poloxamer 407 cubic nanoparticles. Int J Nanomedicine. 2010;5:13–23.PubMedGoogle Scholar
  86. 86.
    Parhi P, Mohanty C, Sahoo SK. Enhanced cellular uptake and in vivo pharmacokinetics of rapamycin-loaded cubic phase nanoparticles for cancer therapy. Acta Biomater. 2011;7:3656–69.PubMedGoogle Scholar
  87. 87.
    Luo Y, Chen D, et al. Solid lipid nanoparticles for enhancing vinpocetine's oral bioavailability. J Control Release. 2006;114:53–9.PubMedGoogle Scholar
  88. 88.
    Hu L, Tang X, et al. Solid lipid nanoparticles (SLNs) to improve oral bioavailability of poorly soluble drugs. J Pharm Pharmacol. 2004;56:1527–35.PubMedGoogle Scholar
  89. 89.
    Venkateswarlu V, Manjunath K. Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles. J Control Release. 2004;95:627–38.PubMedGoogle Scholar
  90. 90.
    Suresh G, Manjunath K, et al. Preparation, characterization, and in vitro and in vivo evaluation of lovastatin solid lipid nanoparticles. AAPS PharmSciTech. 2007;8:24.PubMedGoogle Scholar
  91. 91.
    Pandey R, Sharma S, et al. Oral solid lipid nanoparticle-based antitubercular chemotherapy. Tuberculosis (Edinb). 2005;85:415–20.Google Scholar
  92. 92.
    Hainfeld JF, Slatkin DN, Smilowitz HM. The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol. 2004;49:N309–15.PubMedGoogle Scholar
  93. 93.
    Joshi HM, Bhumkar DR, Joshi K, Pokharkar V, Sastry M. Gold nanoparticles as carriers for efficient transmucosal insulin delivery. Langmuir. 2006;22:300–5.PubMedGoogle Scholar
  94. 94.
    Hillyer JF, Albrecht RM. Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles. J Pharm Sci. 2001;90:1927–36.PubMedGoogle Scholar
  95. 95.
    Stern A, Rotem D, Popov I, Porath D. Quasi 3D imaging of DNA-gold nanoparticle tetrahedral structures. J Phys Condens Matter. 2012;24:164203.PubMedGoogle Scholar
  96. 96.
    You C, Agasti S, Park M, Rotello V. Chemical and biological sensing based on gold nanoparticles. In: Mattoussi H, Cheon J, editors. Inorganic nanoprobes for biological sensing and imaging. Norwood: Artech House Inc.; 2009. p. 161–95.Google Scholar
  97. 97.
    Jana N, Gearheart L, Murphy C. Seed-mediated growth approach for shape-controlled synthesis of spheroidal and rod-like gold nanoparticles using a surfactant template. Adv Mater. 2001;13:1389–93.Google Scholar
  98. 98.
    Shukla R, Bansal V, Chaudhary M, Basu A, Bhonde RR, Sastry M. Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopic overview. Langmuir. 2005;21:10644–54.PubMedGoogle Scholar
  99. 99.
    Connor EE, Mwamuka J, Gole A, Murphy CJ, Wyatt MD. Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small. 2005;1:325–7.PubMedGoogle Scholar
  100. 100.
    Dhar S, Reddy EM, Prabhune A, Pokharkar V, Shiras A, Prasad BLV. Cytotoxicity of sophorolipid-gellan gum-gold nanoparticle conjugates and their doxorubicin loaded derivatives towards human glioma and human glioma stem cell lines. Nanoscale. 2011;3:575–80.PubMedGoogle Scholar
  101. 101.
    Zhang X, Wu H, Wu D, Wang Y, Chang J, Zhai Z, et al. Toxicologic effects of gold nanoparticles in vivo by different administration routes. Int J Nanomedicine. 2010;5:771–81.PubMedGoogle Scholar
  102. 102.
    Liu Y, Miyoshi H, Nakamura M. Novel drug delivery system of hollow mesoporous silica nanocapsules with thin shells: preparation and fluorescein isothiocyanate (FITC) release kinetics. Colloids Surf B Biointerfaces. 2007;58:180–7.PubMedGoogle Scholar
  103. 103.
    Moulari B, Pertuit D, Pellequer Y, Lamprecht A. The targeting of surface modified silica nanoparticles to inflamed tissue in experimental colitis. Biomaterials. 2008;29:4554–60.PubMedGoogle Scholar
  104. 104.
    Chang J, Chang KLB, Hwang D, Kong Z. In vitro cytotoxicitiy of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line. Environ Sci Technol. 2007;41:2064–8.PubMedGoogle Scholar
  105. 105.
    Beck J, Vartuli J, Roth W, Leonowicz M, Kresge C, Schmitt K, et al. A new family of mesoporous molecular sieves prepared with liquid crystal templates. J Am Chem Soc. 1992;114:10834–43.Google Scholar
  106. 106.
    Vallet-Regí M, Balas F, Arcos D. Mesoporous materials for drug delivery. Angew Chem Int Ed Engl. 2007;46:7548–58.PubMedGoogle Scholar
  107. 107.
    Charnay C, Bégu S, Tourné-Péteilh C, Nicole L, Lerner DA, Devoisselle JM. Inclusion of ibuprofen in mesoporous templated silica: drug loading and release property. Eur J Pharm Biopharm. 2004;57:533–40.PubMedGoogle Scholar
  108. 108.
    Zhang Y, Zhi Z, Jiang T, Zhang J, Wang Z, Wang S. Spherical mesoporous silica nanoparticles for loading and release of the poorly water-soluble drug telmisartan. J Control Release. 2010;145:257–63.PubMedGoogle Scholar
  109. 109.
    Li Z, Zhu S, Gan K, Zhang Q, Zeng Z, Zhou Y, et al. Poly-L-lysine-modified silica nanoparticles: a potential oral gene delivery system. J Nanosci Nanotechnol. 2005;5:1199–203.PubMedGoogle Scholar
  110. 110.
    Balas F, Manzano M, Horcajada P, Vallet-Regí M. Confinement and controlled release of bisphosphonates on ordered mesoporous silica-based materials. J Am Chem Soc. 2006;128:8116–7.PubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2012

Authors and Affiliations

  • Roudayna Diab
    • 1
    Email author
  • Chiraz Jaafar-Maalej
    • 2
  • Hatem Fessi
    • 2
  • Philippe Maincent
    • 1
  1. 1.Pharmaceutical Technology Group, CITHÉFOR EA 3452, Faculty of PharmacyUniversity of LorraineNancy CedexFrance
  2. 2.Pharmaceutical Technology Group, LAGEP, UMR CNRS 5007, ISPBL-Faculty of PharmacyUniversity of LyonVilleurbanneFrance

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