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Nano/Microparticles for Retina and Posterior Diseases

  • Anita Patel
  • Jayvadan K. Patel
  • Elie Beit-Yannai
Chapter

Abstract

Treatment and management of diseases of the posterior segment of the eye such as age-related macular degeneration, cytomegalovirus retinitis, diabetic retinopathy, posterior uveitis, retinoblastoma, retinitis pigmentosa, and choroidal neovascularization is a challenging task due to the anatomy and physiology of ocular barriers. For instance, traditional routes of drug delivery for therapeutic treatment are hindered by poor intraocular penetration and/or rapid ocular elimination. One possible approach to improve ocular therapy is to employ nanotechnology. In this chapter, the focus will be on the products of nanotechnology, having at least one dimension in the nanoscale including nano/microparticles with and without targeting ligands, which are making a significant impact in the fields of ocular drug delivery and gene delivery. Additionally, the use of nano/micro-carriers, such as cyclodextrin nanoparticle, polymeric nanoparticle, and functionalized nanoparticle for the treatment of retinal and posterior diseases, has been discussed. Although the above nano/microparticles may be administered by various routes including topical, intravenous, intravitreal, and periocular, each nano/microparticles should be tailored for the disease, drug, and site of administration. In addition, recent advances in the research and development of drug delivery methods of the posterior chamber of the eye, with an emphasis on the use of nano/microparticles, have been summarized.

Keywords

Posterior segment Ocular barrier Nano/micro-carriers Biodegradable 

References

  1. 1.
    Amrite AC, Kompella UB. Nanoparticles for ocular drug delivery. In: Gupta RB, Kompella UB, editors. Nanoparticle technology for drug delivery. New York, NY: Informa Healthcare USA Inc.; 2006. p. 319–60.Google Scholar
  2. 2.
    Raghava S, Goel G, Kompella UB. Ophthalmic applications of nanotechnology. In: Tombran-Tink J, Barnstable CJ, editors. Ocular transporters in ophthalmic diseases and drug delivery. Totowa: Humana Press; 2008. p. 415–36.CrossRefGoogle Scholar
  3. 3.
    Bourges JL, Bloquel C, Thomas A, Froussart F, Bochot A, Azan F, Gurny R, BenEzra D, Behar-Cohen F. Intraocular implants for extended drug delivery: therapeutic applications. Adv Drug Deliv Rev. 2006;58:1182–202.CrossRefGoogle Scholar
  4. 4.
    Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J. 2010;12:348–60.CrossRefGoogle Scholar
  5. 5.
    Liu S, Jones L, Gu FX. Nanomaterials for ocular drug delivery. Macromol Biosci. 2012;12:608–20.CrossRefGoogle Scholar
  6. 6.
    Del Amo EM, Urtti A. Current and future ophthalmic drug delivery systems. A shift to the posterior segment. Drug Discov Today. 2008;13:135–43.CrossRefGoogle Scholar
  7. 7.
    Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev. 2006;58:1131–5.CrossRefGoogle Scholar
  8. 8.
    Hämäläinen KM, Kontturi K, Auriola S, Murtomäki L, Urtti A. Estimation of pore size and pore density of biomembranes from permeability measurements of polyethylene glycols using an effusion-like approach. J Control Release. 1997;49:97–104.CrossRefGoogle Scholar
  9. 9.
    Prausnitz MR, Noonan JS. Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug delivery to the eye. J Pharm Sci. 1998;87:1479–87.CrossRefGoogle Scholar
  10. 10.
    Mannermaa E, Vellonen KS, Urtti A. Drug transport in corneal epithelium and blood–retina barrier: emerging role of transporters in ocular pharmacokinetics. Adv Drug Deliv Rev. 2006;58:1136–63.CrossRefGoogle Scholar
  11. 11.
    Barar J, Javadzadeh AR, Omidi Y. Ocular novel drug delivery: impacts of membranes and barriers. Expert Opin Drug Deliv. 2008;5:567–81.CrossRefGoogle Scholar
  12. 12.
    Gaudana R, Jwala J, Boddu SH, Mitra AK. Recent perspectives in ocular drug delivery. Pharm Res. 2009;26:1197–216.CrossRefGoogle Scholar
  13. 13.
    Klyce SD, Crosson CE. Transport processes across the rabbit corneal epithelium: a review. Curr Eye Res. 1985;4:323–31.CrossRefGoogle Scholar
  14. 14.
    Ghate D, Edelhauser HF. Ocular drug delivery. Expert Opin Drug Deliv. 2006;3:275–87.CrossRefGoogle Scholar
  15. 15.
    Hämäläinen KM, Kananen K, Auriola S, Kontturi K, Urtti A. Characterization of paracellular and aqueous penetration routes in cornea conjunctiva, and sclera. Invest Ophthalmol Vis Sci. 1997b;38:627–34.PubMedGoogle Scholar
  16. 16.
    Holland GN, Sakamoto MJ, Hardy D, Sidikaro Y, Kreiger AE, Frenkel LM. Treatment of cytomegalovirus retinopathy in patients with acquired immunodeficiency syndrome. Use of the experimental drug 9-2-hydroxy-1-(hydroxymethyl)ethoxymethyl guanine. Arch Ophthalmol. 1986;104:1794–800.CrossRefGoogle Scholar
  17. 17.
    Akula SK, Peyman GA, Rahimy MH, Hyslop NE, Janney A, Ashton P. Treatment of cytomegalovirus retinitis with intravitreal injection of liposome encapsulated ganciclovir in a patient with AIDS. Br J Ophthalmol. 1994;78:667–80.CrossRefGoogle Scholar
  18. 18.
    MacCumber MW, Sadeghi S, Cohen JA, Deutsch TA. Suture loop to aid in ganciclovir implant removal. Arch Ophthalmol. 1999;117:1250–4.CrossRefGoogle Scholar
  19. 19.
    Smith TJ, Pearson PA, Blanford DL, Brown JD, Goins KA, Hollins JL, Schmeisser ET, Glavinos P, Baldwin LB, Ashton P. Intravitreal sustained-release ganciclovir. Arch Ophthalmol. 1992;110:255–8.CrossRefGoogle Scholar
  20. 20.
    Yang CS, Khawly JA, Hainsworth DP, Chen SN, Ashton P, Guo H, Jaffe GJ. An intravitreal sustained-release triamcinolone and 5-fluorouracil co-drug in the treatment of experimental proliferative vitreoretinopathy. Arch Ophthalmol. 1998;116:69–77.CrossRefGoogle Scholar
  21. 21.
    Kaur IP, Kanwar M. Ocular preparations: the formulation approach. Drug Dev Ind Pharm. 2002;28:473–93.CrossRefGoogle Scholar
  22. 22.
    Keister JC, Cooper ER, Missel PJ, Lang JC, Hager DF. Limits on optimizing ocular drug delivery. J Pharm Sci. 1991;80:50–3.CrossRefGoogle Scholar
  23. 23.
    Lang JC, Roehrs RE, Jani R. Ophthalmic preparations. In: Beringer P, Gupta PK, editors. Remington, the science and practice of pharmacy. 21st ed. Philadelphia: Lippincott Williams & Williams; 2006. p. 850–70.Google Scholar
  24. 24.
    Rache JM, Merodio M, Arnedo A, Camapanero MA, Mirshahi M, Espuelas S. Albumin nanoparticles for the intravitreal delivery of anticytomegaloviral drugs. Mini-Rev Med Chem. 2005;5:293–305.CrossRefGoogle Scholar
  25. 25.
    de Kozak Y, Andrieux K, Villarroya H, Klein C, Thillaye-Goldenberg B, Naud MC, Garcia E, Couvreur P. Intraocular injection of tamoxifen-loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitis. Eur J Immunol. 2004;34:3702–12.CrossRefGoogle Scholar
  26. 26.
    Yasukawa T, Ogura Y, Tabata Y, Kimura H, Wiedemann P, Honda Y. Drug delivery systems for vitreoretinal diseases. Prog Retin Eye Res. 2004;23:253–81.CrossRefGoogle Scholar
  27. 27.
    Sánchez A, Alonso MJ. Nanoparticular carriers for ocular drug delivery. In: Torchilin VP, editor. Nanoparticulates as drug carriers. London: Imperial College Press; 2006. p. 649–73.CrossRefGoogle Scholar
  28. 28.
    Geroski DH, Edelhauser HF. Transscleral drug delivery for posterior segment disease. Adv Drug Deliv Rev. 2001;52:37–48.CrossRefGoogle Scholar
  29. 29.
    Guidetti B, Azema J, Malet-Martino M, Martino R. Delivery systems for the treatment of proliferative vitreoretinopathy: materials, devices and colloidal carriers. Curr Drug Deliv. 2008;5:7–19.CrossRefGoogle Scholar
  30. 30.
    Kearns VR, Williams RL. Drug delivery systems for the eye. Expert Rev Med Devices. 2009;6:277–90.CrossRefGoogle Scholar
  31. 31.
    Kashyap N, Modi S, Jain JP, Bala I, Hariharan S, Bharadwaj R, Singh D, Mahajan R, Kumar N, Kumar MNVR. Polymers for advanced drug delivery. CRIPS (Current Research and Information on Pharmaceutical Science). 2004;5:7–12.Google Scholar
  32. 32.
    Kranz H, Ubrich N, Maincent P, Bodmeier R. Physicomechanical properties of biodegradable poly (d,l-lactide) and poly(d,l-lactide-co-glycolide) films in the dry and wet states. J Pharm Sci. 2000;89:1558–66.CrossRefGoogle Scholar
  33. 33.
    Dobrovolskaia MA, Aggarwal P, Hall JB, McNeil SE. Preclinical studies to understand nanoparticles interaction with the immune system and its potential effects on nanoparticles biodistribution. Mol Pharm. 2008;5:487–95.CrossRefGoogle Scholar
  34. 34.
    Dobrovolskaia MA, McNeil SE. Immunological properties of engineered nanomaterials. Nat Nanotechnol. 2007;2:469–78.CrossRefGoogle Scholar
  35. 35.
    Durairaj C, Shah JC, Senapati S, Kompella UB. Prediction of vitreal half-life based on drug physicochemical properties: quantitative structure pharmacokinetic relationships (QSPKR). Pharm Res. 2009;26:1236–60.CrossRefGoogle Scholar
  36. 36.
    Andrew JS, Anglin EJ, Wu EC, Chen MY, Cheng L, Freeman WR, Sailor MJ. Sustained release of a monoclonal antibody from electrochemically prepared mesoporous silicon oxide. Adv Funct Mater. 2010;20:4168–74.CrossRefGoogle Scholar
  37. 37.
    Kim H, Robinson SB, Csaky KG. Investigating the movement of intravitreal human serum albumin nanoparticles in the vitreous and retina. Pharm Res. 2009;26:329–37.CrossRefGoogle Scholar
  38. 38.
    Amrite AC, Edelhauser HF, Singh SR, Kompella UB. Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration. Mol Vis. 2008;14:150–60.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Amrite AC, Kompella UB. Size-dependent disposition of nanoparticles and microparticles following subconjunctival administration. J Pharm Pharmacol. 2005;57:1555–63.CrossRefGoogle Scholar
  40. 40.
    Patel SR, Berezovsky DE, McCarey BE, Zarnitsyn V, Edelhauser HF, Prausnitz MR. Targeted administration into the suprachoroidal space using a microneedle for drug delivery to the posterior segment of the eye. Invest Ophthalmol Vis Sci. 2012;53:4433–41.CrossRefGoogle Scholar
  41. 41.
    Kiernan DF, Lim JI. Topical drug delivery for posterior segment disease: novel formulations offer possibilities for efficacious therapies through topical routes. Retina Today. 2010;5:48–54.Google Scholar
  42. 42.
    Janoria KG, Gunda S, Boddu SH, Mitra AK. Novel approaches to retinal drug delivery. Expert Opin Drug Deliv. 2007;4:371–88.CrossRefGoogle Scholar
  43. 43.
    Cholkar K, Patel A, Vadlapudi AD, Mitra AK. Novel nanomicellar formulation approaches for anterior and posterior segment ocular drug delivery. Recent Pat Nanomed. 2012;2:82–95.CrossRefGoogle Scholar
  44. 44.
    Mains J, Wilson CG. The vitreous humor as a barrier to nanoparticle distribution. J Ocul Pharmacol Ther. 2013;29:143–50.CrossRefGoogle Scholar
  45. 45.
    Maurice D. Review: practical issues in intravitreal drug delivery. J Ocul Pharmacol Ther. 2001;17:393–401.CrossRefGoogle Scholar
  46. 46.
    Ranta VP, Mannermaa E, Lummepuro K, Subrizi A, Laukkanen A, Antopolsky M, Murtomäki L, Hornof M, Urtti A. Barrier analysis of periocular drug delivery to the posterior segment. J Control Release. 2010;148:42–8.CrossRefGoogle Scholar
  47. 47.
    Raghava S, Hammond M, Kompella UB. Periocular routes for retinal drug delivery. Expert Opin Drug Deliv. 2004;1:99–114.CrossRefGoogle Scholar
  48. 48.
    da Silva GR, Sílvia LF, Siqueira RC, Jorge R, da Silva ACJ. Implants as drug delivery devices for the treatment of eye diseases. Braz J Pharm Sci. 2010;46:585–95.CrossRefGoogle Scholar
  49. 49.
    Patel SR, Lin AS, Edelhauser HF, Prausnitz MR. Suprachoroidal drug delivery to the back of the eye using hollow microneedles. Pharm Res. 2011;28:166–76.CrossRefGoogle Scholar
  50. 50.
    Mac Gabhann F, Demetriades AM, Deering T, Packer JD, Shah SM, Duh E, Campochiaro PA, Popel AS. Protein transport to choroid and retina following periocular injection: theoretical and experimental study. Ann Biomed Eng. 2007;35:615–30.CrossRefGoogle Scholar
  51. 51.
    Eljarrat-Binstock E, Pe’er J, Domb AJ. New techniques for drug delivery to the posterior eye segment. Pharm Res. 2010;27:530–43.CrossRefGoogle Scholar
  52. 52.
    Diebold Y, Calonge M. Applications of nanoparticles in ophthalmology. Prog Retin Eye Res. 2010;29:596–609.CrossRefGoogle Scholar
  53. 53.
    Bejjani RA, BenEzra D, Cohen H, Rieger J, Andrieu C, Jeaanny J-C, Golomb G, Behar-Cohen FF. Nanoparticles for gene delivery to retinal pigment epithelial cells. Mol Vis. 2005;11:124–32.PubMedGoogle Scholar
  54. 54.
    Bourges JL, Gautier SE, Delie F, Bejjani RA, Jeanny J-C, Gurny R, BenEzra D, Behar-Cohen FF. Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles. Invest Ophthalmol Vis Sci. 2003;44:3562–9.CrossRefGoogle Scholar
  55. 55.
    Normand N, Valamanesh F, Savoldelli M, Mascarelli F, BenEzra D, Courtois Y, Behar-Cohen FF. VP22 light controlled delivery of oligonucleotides to ocular cells in vitro and in vivo. Mol Vis. 2005;11:184–91.PubMedGoogle Scholar
  56. 56.
    Ceulemans J, Ludwig A. Optimisation of carbomer viscous eye drops: an in vitro experimental design approach using rheological techniques. Eur J Pharm Biopharm. 2002;54:41–50.CrossRefGoogle Scholar
  57. 57.
    Durrani AM, Farr SJ, Kellaway IW. Precorneal clearance of mucoadhesive microspheres from the rabbit eye. J Pharm Pharmacol. 1995;47:581–4.CrossRefGoogle Scholar
  58. 58.
    Hornof M, Weyenberg W, Ludwig A, Bernkop-Schnurch A. Mucoadhesive ocular insert based on thiolated poly(acrylic acid): development and in vivo evaluation in humans. J Control Release. 2003;89:419–28.CrossRefGoogle Scholar
  59. 59.
    Lehr CM, Lee YH, Lee VH. Improved ocular penetration of gentamicin by mucoadhesive polymer polycarbophil in the pigmented rabbit. Invest Ophthalmol Vis Sci. 1994;35:2809–14.PubMedGoogle Scholar
  60. 60.
    Yang H, Tyagi P, Kadam RS, Holden CA, Kompella UB. A hybrid dendrimer hydrogel/PLGA nanoparticle platform sustains drug delivery for one week and Antiglaucoma effects for four days following one-time topical administration. ACS Nano. 2012;6:7595–606.CrossRefGoogle Scholar
  61. 61.
    De Campos AM, Sanchez A, Alonso MJ. Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin a. Int J Pharm. 2001;224:159–68.CrossRefGoogle Scholar
  62. 62.
    Ciechanover A, Schwartz AL, Lodish HF. Sorting and recycling of cell surface receptors and endocytosed ligands: the asialoglycoprotein and transferrin receptors. J Cell Biochem. 1983;23:107–30.CrossRefGoogle Scholar
  63. 63.
    Koushik K, Bandi N, Sundaram S, Kompella UB. Evidence for LHRH-receptor expression in human airway epithelial (Calu-3) cells and its role in the transport of an LHRH agonist. Pharm Res. 2004;21:1034–46.CrossRefGoogle Scholar
  64. 64.
    Kompella UB, Sundaram S, Raghava S, Escobar ER. Luteinizing hormone-releasing hormone agonist and transferrin functionalizations enhance nanoparticle delivery in a novel bovine ex vivo eye model. Mol Vis. 2006;12:1185–98.PubMedGoogle Scholar
  65. 65.
    Amrite AC, Ayalasomayajula SP, Cheruvu NP, Kompella UB. Single periocular injection of celecoxib–PLGA microparticles inhibits diabetes-induced elevations in retinal PGE2, VEGF, and vascular leakage. Invest Ophthalmol Vis Sci. 2006;47:1149–60.CrossRefGoogle Scholar
  66. 66.
    Carrasquillo KG, Ricker JA, Rigas IK, Miller JW, Gragoudas ES, Adamis AP. Controlled delivery of the anti-VEGF aptamer EYE001 with poly(lactic-co-glycolic)acid microspheres. Invest Ophthalmol Vis Sci. 2003;44:290–9.CrossRefGoogle Scholar
  67. 67.
    Kompella UB, Bandi N, Ayalasomayajula SP. Subconjunctival nano-and microparticles sustain retinal delivery of budesonide, a corticosteroid capable of inhibiting VEGF expression. Invest Ophthalmol Vis Sci. 2003;44:1192–201.CrossRefGoogle Scholar
  68. 68.
    Saishin Y, Silva RL, Saishin Y, Callahan K, Schoch C, Ahlheim M, Lai H, Kane F, Brazzell RK, Bodmer D, Campochiaro PA. Periocular injection of microspheres containing PKC412 inhibits choroidal neovascularization in a porcine model. Invest Ophthalmol Vis Sci. 2003;44:4989–93.CrossRefGoogle Scholar
  69. 69.
    Christie JG, Kompella UB. Ophthalmic light sensitive nanocarrier systems. Drug Discov Today. 2008;13:124–34.CrossRefGoogle Scholar
  70. 70.
    Fujii Y, Kachi S, Ito A, Kawasumi T, Honda H, Terasaki H. Transfer of gene to human retinal pigment epithelial cells using magnetite cationic liposomes. Br J Ophthalmol. 2010;94:1074–7.CrossRefGoogle Scholar
  71. 71.
    Holden CA, Tyagi P, Thakur A, Kadam R, Jadhav G, Kompella UB, Yang H. Polyamidoamine dendrimer hydrogel for enhanced delivery of antiglaucoma drugs. Nanomedicine. 2012;8:776–83.CrossRefGoogle Scholar
  72. 72.
    Chen J, Patil S, Seal S, McGinnis JF. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nat Nanotechnol. 2006;1:142–50.CrossRefGoogle Scholar
  73. 73.
    Edelhauser HF, Boatright JH, Nickerson JM. Drug delivery to posterior intraocular tissues: third annual ARVO/Pfizer Ophthalmics research institute conference. Invest Ophthalmol Vis Sci. 2008;49:4712–20.CrossRefGoogle Scholar
  74. 74.
    Tamboli V, Patel S, Mishra GP, Mitra AK. Biodegradable polymers for ophthalmic applications. In: Mitra AK, editor. (E-book). Treatise on ocular drug delivery. Bentham: Science Publishers; 2013. p. 96–113. (Chapter 5).CrossRefGoogle Scholar
  75. 75.
    De Campos AM, Diebold Y, Carvalho EL, Sánchez A, Alonso MJ. Chitosan nanoparticles as new ocular drug delivery systems: in Vitro stability, in vivo fate, and cellular toxicity. Pharm Res. 2004;21:803–10.CrossRefGoogle Scholar
  76. 76.
    Aşık MD, Uğurlu N, Yülek F, Tuncer S, Türk M, Denkbaş EB. Ketorolac tromethamine loaded chitosan nanoparticles as a nanotherapeutic system for ocular diseases. Hacettepe J Biol Chem. 2013;41:81–6.Google Scholar
  77. 77.
    Rajendran NN, Natrajan R, Kumar RS, Selvaraj S. Acyclovir loaded chitosan nanoparticles for ocular delivery. Asian J Pharmacol. 2010;4:220–6.CrossRefGoogle Scholar
  78. 78.
    Silva NC, Silva S, Sarmento B, Pintado M. Chitosan nanoparticles for daptomycin delivery in ocular treatment of bacterial endophthalmitis. Drug Deliv. 2015;22:885–93.CrossRefGoogle Scholar
  79. 79.
    Motwani SK, Chopra S, Talegaonkar S, Kohli K, Ahmad FJ, Khar RK. Chitosan-sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: formulation, optimisation and in vitro characterisation. Eur J Pharm Biopharm. 2008;68:513–25.PubMedGoogle Scholar
  80. 80.
    Nagarwal RC, Kumar R, Pandit JK. Chitosan coated sodium alginate- chitosan nanoparticles loaded with 5-FU for ocular delivery: In vitro characterization and in vivo study in rabbit eye. Eur J Pharm Sci. 2012;47:678–85.CrossRefGoogle Scholar
  81. 81.
    Wadhwa S, Paliwal R, Paliwal SR, Vyas SP. Hyaluronic acid modified chitosan nanoparticles for effective management of glaucoma: development, characterization, and evaluation. J Drug Target. 2010;18:292–302.CrossRefGoogle Scholar
  82. 82.
    Qian L, Zheng J, Wang K, Tang Y, Zhang X, Zhang H, Huang F, Pei Y, Jiang Y. Cationic coreshell nanoparticles with carmustine contained within O6-benzylguanine shell for glioma therapy. Biomaterials. 2013;34:8968–78.CrossRefGoogle Scholar
  83. 83.
    Gomez-Gaete C, Tsapis N, Besnard M, Bochot A, Fattal E. Encapsulation of dexamethasone into biodegradable polymeric nanoparticles. Int J Pharm. 2007;331:153–9.CrossRefGoogle Scholar
  84. 84.
    Loftsson T, Hreinsdottir D, Stefansson E. Cyclodextrin microparticles for drug delivery to the posterior segment of the eye: aqueous dexamethasone eye drops. J Pharm Pharmacol. 2007;59:629–35.CrossRefGoogle Scholar
  85. 85.
    Cortesi R, Ajanji SC, Sivieri E, Manservigi M, Fundueanu G, Menegatti E, Esposito E. Eudragit microparticles as a possible tool for ophthalmic administration of acyclovir. J Microencapsul. 2007;24:445–56.CrossRefGoogle Scholar
  86. 86.
    Sakai T, Kohno H, Ishihara T, Higaki M, Saito S, Matsushima M, Mizushima Y, Kitahara K. Treatment of experimental autoimmune uveoretinitis with poly (lactic acid) nanoparticles encapsulating β-methasone phosphate. Exp Eye Res. 2006;82:657–63.CrossRefGoogle Scholar
  87. 87.
    Ayalasomayajula SP, Kompella UB. Subconjunctivally administered celecoxib-PLGA microparticles sustain retinal drug levels and alleviate diabetes-induced oxidative stress in a rat model. Eur J Pharmacol. 2005;511:191–8.CrossRefGoogle Scholar
  88. 88.
    Panyam J, Zhou WZ, Prabha S, Sahoo SK, Labhasetwar V. Rapid endo-lysosomal escape of poly(dllactide-co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB J. 2002;16:1217–26.CrossRefGoogle Scholar
  89. 89.
    Mo Y, Barnett ME, Takemoto D, Davidson H, Kompella UB. Human serum albumin nanoparticles for efficient delivery of cu, Zn superoxide dismutase gene. Mol Vis. 2007;13:746–57.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Singh SR, Grossniklaus HE, Kang SJ, Edelhauser HF, Ambati BK, Kompella UB. Intravenous transferrin, RGD peptide and dual-targeted nanoparticles enhance anti-VEGF intraceptor gene delivery to laser-induced CNV. Gene Ther. 2009;16:645–59.CrossRefGoogle Scholar
  91. 91.
    McNeil SE. Nanotechnology for the biologist. J Leukoc Biol. 2005;78(3):585–94.CrossRefGoogle Scholar
  92. 92.
    Kipen HM, Laskin DL. Smaller is not always better: nanotechnology yields nanotoxicology. Am J Physiol Lung Cell Mol Physiol. 2005;289:L696–7.CrossRefGoogle Scholar
  93. 93.
    Kiang T, Brigth C, Cheung CY, Stayton PS, Hoffman AS, Leong KW. Formulation of chitosan-DNA nanoparticles with poly(propyl acrylic acid) enhances gene expression. J Biomater Sci Polym Ed. 2004;15:1405–21.CrossRefGoogle Scholar
  94. 94.
    Akagi T, Kim H, Akashi M. pH-dependent disruption of erythrocyte membrane by amphiphilic poly(amino acid) nanoparticles. J Biomater Sci Polym Ed. 2010;21:315–28.CrossRefGoogle Scholar
  95. 95.
    Medina C, Santos-Martínez MJ, Radomski A, Corrigan OI, Radomski MW. Nanoparticles: pharmacological and toxicological significance. Br J Pharmacol. 2007;150:552–8.CrossRefGoogle Scholar
  96. 96.
    Zolnik BS, González-Fernández A, Sadrieh N, Dobrovolskaia MA. Mini review: nanoparticles and the immune system. Endocrinology. 2010;151:458–65.CrossRefGoogle Scholar
  97. 97.
    Manolova V, Flace A, Bauer M, Schwarz K, Saudan P, Bachmann MF. Nanoparticles target distinct dendritic cell populations according to their size. Eur J Immunol. 2008;38:1404–13.CrossRefGoogle Scholar
  98. 98.
    Reddy ST, van der Vlies AJ, Simeoni E, Angeli V, Randolph GJ, O’Neil CP, Lee LK, Swartz MA, Hubbell JA. Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nat Biotechnol. 2007;25:1159–64.CrossRefGoogle Scholar
  99. 99.
    Putman E, van der Laan JW, van Loveren H. Assessing immunotoxicity: guidelines. Fundam Clin Pharmacol. 2003;17:615–26.CrossRefGoogle Scholar
  100. 100.
    Snodin DJ. Regulatory immunotoxicology: does the published evidence support mandatory nonclinical immune function screening in drug development? Regul Toxicol Pharmacol. 2004;40:336–55.CrossRefGoogle Scholar
  101. 101.
    Stone V, Johnston H, Schins RP. Development of in vitro systems for nanotoxicology: methodological considerations. Crit Rev Toxicol. 2009;39:613–26.CrossRefGoogle Scholar
  102. 102.
    NCL. National Characterization Laboratory, U.S. National Cancer Institute http://ncl.cancer.gov/working_assay-cascade.asp. 2004. Accessed 21 April 2017.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Anita Patel
    • 1
  • Jayvadan K. Patel
    • 1
  • Elie Beit-Yannai
    • 2
  1. 1.Nootan Pharmacy College, Faculty of PharmacySankalchand Patel UniversityVisnagarIndia
  2. 2.Clinical Pharmacology, Ben-Gurion University of the NegevBeer-ShevaIsrael

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