Polymeric Nanoparticles

  • Ijeoma F. Uchegbu
  • Aikaterini Lalatsa
  • Dennis Wong


Self-assembling polymers, which are either amphiphilic block copolymers with hydrophobic and hydrophilic blocks, hydrophilic polymer backbones substituted with hydrophobic units or polymers with a low aqueous solubility, may all be used to prepare aqueous dispersions of polymeric nanoparticles. The amphiphilic variants form polymeric micelles and polymeric bilayer vesicles. The hydrophobic polymers form dense amorphous polymeric particles. Polymeric particles, of whichever nature, may be loaded with hydrophobic and hydrophilic drugs, and the bioavailability of the drug compound is altered by this encapsulation within a polymeric nanoparticle. This simple concept has been exploited heavily to yield enhancements in oral, tumour and brain bioavailability and some of these polymeric nanoparticle formulations have undergone clinical testing and even been commercialised, e.g. the nanoparticle paclitaxel formulation Abraxane.


Ethylene Oxide Polymeric Micelle Critical Micellar Concentration Polymer Nanoparticles Brain Endothelial Cell 


  1. Adams ML, Andes DR, Kwon GS (2003) Amphotericin B encapsulated in micelles based on poly(ethylene oxide)-block-poly(L-amino acid) derivatives exerts reduced in vitro hemolysis but maintains potent in vivo antifungal activity. Biomacromolecules 4:750–757PubMedCrossRefGoogle Scholar
  2. Alexandridis P, Holzwarth JF, Hatton TA (1994) Micellization of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers in aqueous-solutions—thermodynamics of copolymer association. Macromolecules 27:2414–2425CrossRefGoogle Scholar
  3. Brown MD, Uchegbu IF, Schatzlein AG (1999) Polyamino acid based polymeric vesicles for gene delivery. Br J Cancer 80:P97CrossRefGoogle Scholar
  4. Cheng WP, Gray AI, Tetley L, Hang TLB, Schatzlein AG, Uchegbu IF (2006) Polyelectrolyte nanoparticles with high drug loading enhance the oral uptake of hydrophobic compounds. Biomacromolecules 7:1509–1520PubMedCrossRefGoogle Scholar
  5. Chooi KW, Gray AI, Tetley L, Fan YL, Uchegbu IF (2010) The molecular shape of poly(propyleneimine) dendrimers has a profound effect on their self assembly. Langmuir 26:2301–2316PubMedCrossRefGoogle Scholar
  6. Chooi KW, Hou XL, Qu X, Soundararajan R, Uchegbu IF (2013) Claw amphiphiles with a dendrimer core—nanoparticle stability and drug encapsulation is directly proportional to the number of digits. Langmuir 29(13):4214–4224PubMedCrossRefGoogle Scholar
  7. Cortes J, Saura C (2010) Nanoparticle albumin-bound (nab (TM))-paclitaxel: improving efficacy and tolerability by targeted drug delivery in metastatic breast cancer. EJC Suppl 8:1–10CrossRefGoogle Scholar
  8. Dufes C, Schatzlein AG, Tetley L, Gray AI, Watson DG, Olivier JC, Couet W, Uchegbu IF (2000) Niosomes and polymeric chitosan based vesicles bearing transferrin and glucose ligands for drug targeting. Pharm Res 17:1250–1258PubMedCrossRefGoogle Scholar
  9. Dyer AM, Hinchcliffe M, Watts P, Castile J, Jabbal-Gill I, Nankervis R, Smith A, Illum L (2002) Nasal delivery of insulin using novel chitosan based formulations: a comparative study in two animal models between simple chitosan formulations and chitosan nanoparticles. Pharm Res 19:998–1008PubMedCrossRefGoogle Scholar
  10. Ensign LM, Tang BC, Wang YY, Tse TA, Hoen T, Cone R, Hanes J (2012) Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus. Sci Transl Med 4:138ra79PubMedCrossRefGoogle Scholar
  11. Fu Q, Sun J, Zhang WP, Sui XF, Yan ZT, He ZG (2009) Nanoparticle albumin-bound (NAB) technology is a promising method for anti-cancer drug delivery. Recent Pat Anticancer Drug Discov 4:262–272PubMedCrossRefGoogle Scholar
  12. Garrett NL, Lalatsa A, Uchegbu I, Schatzlein A, Moger J (2012) Exploring uptake mechanisms of oral nanomedicines using multimodal nonlinear optical microscopy. J Biophotonics 5:458–468PubMedCrossRefGoogle Scholar
  13. Gelderblom H, Verweij J, Nooter K, Sparreboom A (2001) Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer 37:1590–1598PubMedCrossRefGoogle Scholar
  14. Ghosh S, Collier A (2007) Inhaled insulins. Postgrad Med J 83:178–181PubMedCrossRefGoogle Scholar
  15. Hrkach J, Von Hoff D, Ali MM, Andrianova E, Auer J, Campbell T, De Witt D, Figa M, Figueiredo M, Horhota A, Low S, McDonnell K, Peeke E, Retnarajan B, Sabnis A, Schnipper E, Song JJ, Song YH, Summa J, Tompsett D, Troiano G, Hoven TV, Wright J, LoRusso P, Kantoff PW, Bander NH, Sweeney C, Farokhzad OC, Langer R, Zale S (2012) Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. Sci Transl Med 4:128ra39PubMedCrossRefGoogle Scholar
  16. Hu QY, Gu GZ, Liu ZY, Jiang MY, Kang T, Miao DY, Tu YF, Pang ZQ, Song QX, Yao L, Xia HM, Chen HZ, Jiang XG, Gao XL, Chen J (2013) F3 peptide-functionalized PEG-PLA nanoparticles co-administrated with tLyp-1 peptide for anti-glioma drug delivery. Biomaterials 34:1135–1145PubMedCrossRefGoogle Scholar
  17. Kataoka K, Matsumoto T, Yokoyama M, Okano T, Sakurai Y, Fukushima S, Okamoto K, Kwon GS (2000) Doxorubicin-loaded poly(ethylene glycol)-poly(beta-benzyl-L-aspartate) copolymer micelles: their pharmaceutical characteristics and biological significance. J Control Release 64:143–153PubMedCrossRefGoogle Scholar
  18. Kim H, Kim Y, Guk K, Yoo D, Lim H, Kang G, Lee D (2012) Fully biodegradable and cationic poly(amino oxalate) particles for the treatment of acetaminophen-induced acute liver failure. Int J Pharm 434:243–250PubMedCrossRefGoogle Scholar
  19. Kim JY, Choi WI, Kim YH, Tae G (2013) Brain-targeted delivery of protein using chitosan- and RVG peptide-conjugated, pluronic-based nano-carrier. Biomaterials 34:1170–1178PubMedCrossRefGoogle Scholar
  20. Kirkpatrick P (2003) Pressures in the pipeline. Nat Rev Drug Discov 2:337CrossRefGoogle Scholar
  21. Kreuter J, Shamenkov D, Petrov V, Ramge P, Cychutek K, Koch-Brandt C, Alyautdin R (2002) Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier. J Drug Target 10:317–325PubMedCrossRefGoogle Scholar
  22. Lalatsa A, Schätzlein AG, Uchegbu IF (2011) Drug delivery across the blood brain barrier. In: MurrayMoo-Young M, Butler M, Webb C et al (eds) Comprehensive biotechnology, 2nd edn. Elsevier, Amsterdam, pp 657–668CrossRefGoogle Scholar
  23. Lalatsa A, Garrett N, Moger J, Schatzlein AG, Davis C, Uchegbu IF (2012a) Delivery of peptides to the blood and brain after oral uptake of quaternary ammonium palmitoyl glycol chitosan nanoparticles. Mol Pharm 9:1764–1774PubMedCrossRefGoogle Scholar
  24. Lalatsa A, Lee V, Malkinson JP, Zloh M, Schatzlein AG, Uchegbu IF (2012b) A prodrug nanoparticle approach for the oral delivery of a hydrophilic peptide, leucine(5)-enkephalin, to the brain. Mol Pharm 9:1665–1680PubMedCrossRefGoogle Scholar
  25. Lalatsa A, Schatzlein AG, Mazza M, Le TB, Uchegbu IF (2012c) Amphiphilic poly(l-amino acids)—new materials for drug delivery. J Control Release 161:523–536PubMedCrossRefGoogle Scholar
  26. Lavasanifar A, Samuel J, Kwon GS (2002) Poly(ethylene oxide)-block-poly(L-amino acid) micelles for drug delivery. Adv Drug Del Rev 54:169–190CrossRefGoogle Scholar
  27. Le TBH, Schatzlein AG, Uchegbu IF (2013) Polymer hydrophobicity has a positive effect on the oral absorption of cyclosporine A from poly(ethylenimine) based nanomedicines. Pharm Nanotechnol 1:15–25Google Scholar
  28. Lee J, Lee C, Kim TH, Lee ES, Shin BS, Chi SC, Park ES, Lee KC, Youn YS (2012) Self-assembled glycol chitosan nanogels containing palmityl-acylated exendin-4 peptide as a long-acting anti-diabetic inhalation system. J Control Release 161:728–734PubMedCrossRefGoogle Scholar
  29. Lv PP, Wei W, Yue H, Yang TY, Wang LY, Ma GH (2011) Porous quaternized chitosan nanoparticles containing paclitaxel nanocrystals improved therapeutic efficacy in non-small-cell lung cancer after oral administration. Biomacromolecules 12:4230–4239PubMedCrossRefGoogle Scholar
  30. Maeda H (1992) The tumor blood vessel as an ideal target for macromolecular anticancer agents. J Control Release 19:315–324CrossRefGoogle Scholar
  31. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumour vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65:271–284PubMedCrossRefGoogle Scholar
  32. Min KH, Park K, Kim YS, Bae SM, Lee S, Jo HG, Park RW, Kim IS, Jeong SY, Kim K, Kwon IC (2008) Hydrophobically modified glycol chitosan nanoparticles-encapsulated camptothecin enhance the drug stability and tumor targeting in cancer therapy. J Control Release 127:208–218PubMedCrossRefGoogle Scholar
  33. Moger J, Garrett NL, Begley D, Mihoreanu L, Lalatsa A, Lozano M, Mazza M, Schatzlein A, Uchegbu IF (2012) Imaging cortical vasculature with stimulated Raman scattering and two photon photothermal lensing microscopy. J Raman Spectrosc 43:668–674CrossRefGoogle Scholar
  34. Mukhopadhyay P, Sarkar K, Chakraborty M, Bhattacharya S, Mishra R, Kundu PP (2013) Oral insulin delivery by self-assembled chitosan nanoparticles: in vitro and in vivo studies in diabetic animal model. Mater Sci Eng C 33:376–382CrossRefGoogle Scholar
  35. Na JH, Lee SY, Lee S, Koo H, Min KH, Jeong SY, Yuk SH, Kim K, Kwon IC (2012) Effect of the stability and deformability of self-assembled glycol chitosan nanoparticles on tumor-targeting efficiency. J Control Release 163:2–9PubMedCrossRefGoogle Scholar
  36. Nakagawa S (2008) Efficacy and safety of poly (gamma-glutamic acid) based nanoparticles (gamma-PGA NPs) as vaccine carrier. Yakugaku Zasshi 128:1559–1565PubMedCrossRefGoogle Scholar
  37. Nishiyama N, Yokoyama M, Aoyagi T, Okano T, Sakurai Y, Kataoka K (1999) Preparation and characterization of self-assembled polymer−metal complex micelle from cis-dichlorodiammineplatinum(II) and poly(ethylene glycol)−poly(α, β-aspartic acid) block copolymer in an aqueous medium. Langmuir 15:377–383CrossRefGoogle Scholar
  38. Nishiyama N, Okazaki S, Cabral H, Miyamoto M, Kato Y, Sugiyama Y, Nishio K, Matsumura Y, Kataoka K (2003) Novel cisplatin-incorporated polymeric micelles can eradicate solid tumors in mice. Cancer Res 63:8977–8983PubMedGoogle Scholar
  39. Podhajcer OL, Benedetti LG, Girotti MR, Prada F, Salvatierra E, Llera AS (2008) The role of the matricellular protein SPARC in the dynamic interaction between the tumor and the host. Cancer Metastasis Rev 27:691–705PubMedCrossRefGoogle Scholar
  40. Qu XZ, Khutoryanskiy VV, Stewart A, Rahman S, Papahadjopoulos-Sternberg B, Dufes C, McCarthy D, Wilson CG, Lyons R, Carter KC, Schatzlein A, Uchegbu IF (2006) Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude. Biomacromolecules 7:3452–3459PubMedCrossRefGoogle Scholar
  41. Qu X, Omar L, Le TBH, Tetley L, Bolton K, Chooi KW, Wang W, Uchegbu IF (2008) Polymeric amphiphile branching leads to rare nano-disc shaped planar self assemblies. Langmuir 24:9997–10004PubMedCrossRefGoogle Scholar
  42. Rafie F, Javadzadeh Y, Javadzadeh AR, Ghavidel LA, Jafari B, Moogooee M, Davaran S (2010) In vivo evaluation of novel nanoparticles containing dexamethasone for ocular drug delivery on rabbit eye. Curr Eye Res 35:1081–1089PubMedCrossRefGoogle Scholar
  43. Sarmento B, Ribeiro A, Veiga F, Sampaio P, Neufeld R, Ferreira D (2007) Alginate/chitosan nanoparticles are effective for oral insulin delivery. Pharm Res 24:2198–2206PubMedCrossRefGoogle Scholar
  44. Seju U, Kumar A, Sawant KK (2011) Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: in vitro and in vivo studies. Acta Biomater 7:4169–4176PubMedCrossRefGoogle Scholar
  45. Shahnaz G, Vetter A, Barthelmes J, Rahmat D, Laffleur F, Iqbal J, Perera G, Schlocker W, Dunnhaput S, Augustijns P, Bernkop-Schnurch A (2012) Thiolated chitosan nanoparticles for the nasal administration of leuprolide: bioavailability and pharmacokinetic characterization. Int J Pharm 428:164–170PubMedCrossRefGoogle Scholar
  46. Siew A, Le H, Thiovolet M, Gellert P, Schatzlein A, Uchegbu I (2012) Enhanced oral absorption of hydrophobic and hydrophilic drugs using quaternary ammonium palmitoyl glycol chitosan nanoparticles. Mol Pharm 9:14–28PubMedCrossRefGoogle Scholar
  47. Strickley RG (2004) Solubilizing excipients in oral and injectable formulations. Pharm Res 21:201–230PubMedCrossRefGoogle Scholar
  48. Tanford C (1980) The hydrophobic effect: formation of micelles and biological membranes. Wiley, New YorkGoogle Scholar
  49. Trapani A, Di Gioia S, Ditaranto N, Cioffi N, Goycoolea FM, Carbone A, Garcia-Fuentes M, Conese M, Alonso MJ (2013) Systemic heparin delivery by the pulmonary route using chitosan and glycol chitosan nanoparticles. Int J Pharm 139:215–218CrossRefGoogle Scholar
  50. Uchegbu IF, Schatzlein AG (2006) Polymers in drug delivery. Taylor and Francis, Boca RatonCrossRefGoogle Scholar
  51. Uchegbu IF, Siew A (2013) Nanomedicines and nanodiagnostics come of age. J Pharm Sci 102:305–310PubMedCrossRefGoogle Scholar
  52. Uchegbu IF, Schatzlein AG, Tetley L, Gray AI, Sludden J, Siddique S, Mosha E (1998) Polymeric chitosan-based vesicles for drug delivery. J Pharm Pharmacol 50:453–458PubMedCrossRefGoogle Scholar
  53. Uchegbu IF, Sadiq L, Arastoo M, Gray AI, Wang W, Waigh RD, Schätzlein AG (2001) Quarternary ammonium palmitoyl glycol chitosan—a new polysoap for drug delivery. Int J Pharm 224:185–199PubMedCrossRefGoogle Scholar
  54. Uchegbu IF, Sadiq L, Pardakhty A, El-Hammadi M, Gray AI, Tetley L, Wang W, Zinselmeyer BH, Schatzlein AG (2004) Gene transfer with three amphiphilic glycol chitosans—the degree of polymerisation is the main controller of transfection efficiency. J Drug Target 12:527–539PubMedCrossRefGoogle Scholar
  55. Uchino H, Matsumura Y, Negishi T, Koizumi F, Hayashi T, Honda T, Nishiyama N, Kataoka K, Naito S, Kakizoe T (2005) Cisplatin-incorporating polymeric micelles (NC-6004) can reduce nephrotoxicity and neurotoxicity of cisplatin in rats. Br J Cancer 93:678–687PubMedCrossRefGoogle Scholar
  56. Van Domeselaar GH, Kwon GS, Andrew LC, Wishart DS (2003) Application of solid phase peptide synthesis to engineering PEO-peptide block copolymers for drug delivery. Colloids Surf B Biointerfaces 30:323–334CrossRefGoogle Scholar
  57. Wadhwa S, Paliwal R, Paliwal SR, Vyas SP (2010) Hyaluronic acid modified chitosan nanoparticles for effective management of glaucoma: development, characterization, and evaluation. J Drug Target 18:292–302PubMedCrossRefGoogle Scholar
  58. Wang W, Tetley L, Uchegbu IF (2000) A new class of amphiphilic poly-L-lysine based polymers forms nanoparticles on probe sonication in aqueous media. Langmuir 16:7859–7866CrossRefGoogle Scholar
  59. Wang W, McConaghy AM, Tetley L, Uchegbu IF (2001a) Controls on polymer molecular weight may be used to control the size of palmitoyl glycol chitosan polymeric vesicles. Langmuir 17:631–636CrossRefGoogle Scholar
  60. Wang W, Tetley L, Uchegbu IF (2001b) The level of hydrophobic substitution and the molecular weight of amphiphilic poly-L-lysine-based polymers strongly affects their assembly into polymeric bilayer vesicles. J Colloid Interface Sci 237:200–207PubMedCrossRefGoogle Scholar
  61. Wang W, Qu XZ, Gray AI, Tetley L, Uchegbu IF (2004) Self-assembly of cetyl linear polyethylenimine to give micelles, vesicles, and dense nanoparticles. Macromolecules 37:9114–9122CrossRefGoogle Scholar
  62. Win KY, Feng SS (2006) In vitro and in vivo studies on vitamin E TPGS-emulsified poly(D, L-lactic-co-glycolic acid) nanoparticles for paclitaxel formulation. Biomaterials 27:2285–2291PubMedCrossRefGoogle Scholar
  63. Wohlfart S, Khalansky AS, Gelperina S, Begley D, Kreuter J (2011) Kinetics of transport of doxorubicin bound to nanoparticles across the blood-brain barrier. J Control Release 154:103–107PubMedCrossRefGoogle Scholar
  64. Yang J, Xie SX, Huang YL, Ling M, Liu JH, Ran YL, Wang YL, Thrasher JB, Berkland C, Li BY (2012) Prostate-targeted biodegradable nanoparticles loaded with androgen receptor silencing constructs eradicate xenograft tumors in mice. Nanomedicine 7:1297–1309PubMedCrossRefGoogle Scholar
  65. Yokoyama M, Fukushima S, Uehara R, Okamoto K, Kataoka K, Sakurai Y, Okano T (1998a) Characterization of physical entrapment and chemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery to a solid tumor. J Control Release 50:79–92PubMedCrossRefGoogle Scholar
  66. Yokoyama M, Satoh A, Sakurai Y, Okano T, Matsumura Y, Kakizoe T, Kataoka K (1998b) Incorporation of water-insoluble anticancer drugs into polymeric micelles and control of their particle. J Control Release 55:219–229PubMedCrossRefGoogle Scholar
  67. Yoon HY, Koo H, Choi KY, Lee SJ, Kim K, Kwon IC, Leary JF, Park K, Yuk SH, Park JH, Choi K (2012) Tumor-targeting hyaluronic acid nanoparticles for photodynamic imaging and therapy. Biomaterials 33:3980–3989PubMedCrossRefGoogle Scholar
  68. Yu BG, Okano T, Kataoka K, Kwon G (1998) Polymeric micelles for drug delivery: solubilization and haemolytic activity of amphotericin B. J Control Release 53:131–136PubMedCrossRefGoogle Scholar
  69. Zensi A, Begley D, Pontikis C, Legros C, Mihoreanu L, Wagner S, Buchel C, von Briesen H, Kreuter J (2009) Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones. J Control Release 137:78–86PubMedCrossRefGoogle Scholar
  70. Zhang Y, Wu XR, Meng LK, Ai RT, Qi N, He HB, Xu H, Tang X (2012) Thiolated Eudragit nanoparticles for oral insulin delivery: preparation, characterization and in vivo evaluation. Int J Pharm 436:341–350PubMedCrossRefGoogle Scholar
  71. Zou AF, Chen Y, Huo MR, Wang J, Zhang Y, Zhou JP, Zhang Q (2013) In vivo studies of octreotide-modified N-octyl-O, N-carboxymethyl chitosan micelles loaded with doxorubicin for tumor-targeted delivery. J Pharm Sci 102:126–135PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ijeoma F. Uchegbu
    • 1
  • Aikaterini Lalatsa
    • 2
  • Dennis Wong
    • 3
  1. 1.UCL School of PharmacyUniversity College LondonLondonUK
  2. 2.School of Pharmacy & Biomedical SciencesUniversity of PortsmouthPortsmouthUK
  3. 3.University of StrathclydeGlasgowUK

Personalised recommendations