Skip to main content

Nanoparticles for Drug and Gene Delivery in Treating Diseases of the Eye

  • Protocol
  • First Online:
Ocular Pharmacology and Toxicology

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Using biodegradable polymeric nanoparticles as model systems for drug and gene delivery, this chapter describes commonly used methods for preparing and characterizing nanoparticles. This chapter focuses on emulsion solvent evaporation-based methods for encapsulating hydrophilic as well as lipophilic drugs in polymeric nanoparticles. In order to describe methods for preparing nanoparticles, we have chosen poly(lactide) (PLA)/poly(lactide-co-glycolide) (PLGA) as the carrier materials for nanoparticles intended for drug and gene delivery. Nanoparticles intended for drug and gene delivery can be characterized for various parameters including particle size, size distribution, morphology, zeta potential, drug loading, syringeability and injectability, in vitro drug release, and stability. Methods for the measurement of these parameters, which influence the performance characteristics of nanoparticles in vivo, are also discussed in this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Akpek EK, Smith RA (2013) Overview of age-related ocular conditions. Am J Manag Care 19(5 Suppl):s67–s75

    PubMed  Google Scholar 

  2. Clark AF, Yorio T (2003) Ophthalmic drug discovery. Nat Rev Drug Discov 2(6):448–459. doi:10.1038/nrd1106

    Article  PubMed  CAS  Google Scholar 

  3. Shah SS, Denham LV, Elison JR, Bhattacharjee PS, Clement C, Huq T, Hill JM (2010) Drug delivery to the posterior segment of the eye for pharmacologic therapy. Exp Rev Ophthalmol 5(1):75–93. doi:10.1586/eop.09.70

    Article  CAS  Google Scholar 

  4. Amrite AC, Ayalasomayajula SP, Cheruvu NP, Kompella UB (2006) Single periocular injection of celecoxib-PLGA microparticles inhibits diabetes-induced elevations in retinal PGE2, VEGF, and vascular leakage. Invest Ophthalmol Vis Sci 47(3):1149–1160. doi:10.1167/iovs.05-0531

    Article  PubMed  Google Scholar 

  5. Kompella UB, Amrite AC, Pacha Ravi R, Durazo SA (2013) Nanomedicines for back of the eye drug delivery, gene delivery, and imaging. Prog Retin Eye Res. doi:10.1016/j.preteyeres.2013.04.001

    PubMed  Google Scholar 

  6. D’Souza SS, DeLuca PP (2006) Methods to assess in vitro drug release from injectable polymeric particulate systems. Pharm Res 23(3):460–474. doi:10.1007/s11095-005-9397-8

    Article  PubMed  Google Scholar 

  7. Singh SR, Grossniklaus HE, Kang SJ, Edelhauser HF, Ambati BK, Kompella UB (2009) Intravenous transferrin, RGD peptide and dual-targeted nanoparticles enhance anti-VEGF intraceptor gene delivery to laser-induced CNV. Gene Ther 16(5):645–659. doi:10.1038/gt.2008.185

    Article  PubMed  CAS  Google Scholar 

  8. Mitra M, Misra R, Harilal A, Sahoo SK, Krishnakumar S (2011) Enhanced in vitro antiproliferative effects of EpCAM antibody-functionalized paclitaxel-loaded PLGA nanoparticles in retinoblastoma cells. Mol Vis 17:2724–2737

    PubMed  CAS  Google Scholar 

  9. Astete CE, Sabliov CM (2006) Synthesis and characterization of PLGA nanoparticles. J Biomater Sci Polym Ed 17(3):247–289

    Article  PubMed  CAS  Google Scholar 

  10. Peyman GA, Yang D, Khoobehi B, Rahimy MH, Chin SY (1996) In vitro evaluation of polymeric matrix and porous biodegradable reservoir devices for slow-release drug delivery. Ophthalmic Surg Lasers 27(5):384–391

    PubMed  CAS  Google Scholar 

  11. Thombre AG, Himmelstein KJ (1984) Modelling of drug release kinetics from a laminated device having an erodible drug reservoir. Biomaterials 5(5):250–254

    Article  PubMed  CAS  Google Scholar 

  12. Richards Grayson AC, Cima MJ, Langer R (2004) Molecular release from a polymeric microreservoir device: Influence of chemistry, polymer swelling, and loading on device performance. J Biomed Mater Res A 69(3):502–512. doi:10.1002/jbm.a.30019

    Article  PubMed  Google Scholar 

  13. Kawashima Y, Yamamoto H, Takeuchi H, Hino T, Niwa T (1998) Properties of a peptide containing dl-lactide/glycolide copolymer nanospheres prepared by novel emulsion solvent diffusion methods. Eur J Pharm Biopharm 45(1):41–48. doi:10.1016/S0939-6411(97)00121-5

    Article  PubMed  CAS  Google Scholar 

  14. Gopferich A (1996) Mechanisms of polymer degradation and erosion. Biomaterials 17(2):103–114

    Article  PubMed  CAS  Google Scholar 

  15. Siepmann J, Elkharraz K, Siepmann F, Klose D (2005) How autocatalysis accelerates drug release from PLGA-based microparticles: a quantitative treatment. Biomacromolecules 6(4):2312–2319. doi:10.1021/bm050228k

    Article  PubMed  CAS  Google Scholar 

  16. Kompella UB, Bandi N, Ayalasomayajula SP (2003) Subconjunctival nano- and microparticles sustain retinal delivery of budesonide, a corticosteroid capable of inhibiting VEGF expression. Invest Ophthalmol Vis Sci 44(3):1192–1201

    Article  PubMed  Google Scholar 

  17. Kadam RS, Tyagi P, Edelhauser HF, Kompella UB (2012) Influence of choroidal neovascularization and biodegradable polymeric particle size on transscleral sustained delivery of triamcinolone acetonide. Int J Pharm 434(1–2):140–147. doi:10.1016/j.ijpharm.2012.05.025

    Article  PubMed  CAS  Google Scholar 

  18. Yang H, Tyagi P, Kadam RS, Holden CA, Kompella UB (2012) 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 6(9):7595–7606. doi:10.1021/nn301873v

    Article  PubMed  CAS  Google Scholar 

  19. Luo L, Zhang X, Hirano Y, Tyagi P, Barabas P, Uehara H, Miya TR, Singh N, Archer B, Qazi Y, Jackman K, Das SK, Olsen T, Chennamaneni SR, Stagg BC, Ahmed F, Emerson L, Zygmunt K, Whitaker R, Mamalis C, Huang W, Gao G, Srinivas SP, Krizaj D, Baffi J, Ambati J, Kompella UB, Ambati BK (2013) Targeted intraceptor nanoparticle therapy reduces angiogenesis and fibrosis in primate and murine macular degeneration. ACS Nano 7(4):3264–3275. doi:10.1021/nn305958y

    Article  PubMed  CAS  Google Scholar 

  20. Cho YK, Uehara H, Young JR, Tyagi P, Kompella UB, Zhang X, Luo L, Singh N, Archer B, Ambati BK (2012) Flt23k nanoparticles offer additive benefit in graft survival and anti-angiogenic effects when combined with triamcinolone. Invest Ophthalmol Vis Sci 53(4):2328–2336. doi:10.1167/iovs.11-8393

    Article  PubMed  Google Scholar 

  21. Panyam J, Dali MM, Sahoo SK, Ma W, Chakravarthi SS, Amidon GL, Levy RJ, Labhasetwar V (2003) Polymer degradation and in vitro release of a model protein from poly(d, l-lactide-co-glycolide) nano- and microparticles. J Control Release 92(1–2):173–187

    Article  PubMed  CAS  Google Scholar 

  22. Amrite AC, Kompella UB (2006) Nanoparticles for ocular drug delivery. In: Gupta RB, Kompella UB (eds) Nanoparticle technology for drug delivery, vol 159. Taylor and Francis Group, New York, pp 319–360

    Chapter  Google Scholar 

  23. Shmueli RB, Bhise NS, Green JJ (2013) Evaluation of polymeric gene delivery nanoparticles by nanoparticle tracking analysis and high-throughput flow cytometry. J Vis Exp (73):e50176. doi:10.3791/50176

  24. Wright M (2012) Nanoparticle tracking analysis for the multiparameter characterization and counting of nanoparticle suspensions. Methods Mol Biol 906:511–524. doi:10.1007/978-1-61779-953-2_41

    PubMed  CAS  Google Scholar 

  25. Zolls S, Tantipolphan R, Wiggenhorn M, Winter G, Jiskoot W, Friess W, Hawe A (2012) Particles in therapeutic protein formulations, Part 1: overview of analytical methods. J Pharm Sci 101(3):914–935. doi:10.1002/jps.23001

    Article  PubMed  Google Scholar 

  26. den Engelsman J, Garidel P, Smulders R, Koll H, Smith B, Bassarab S, Seidl A, Hainzl O, Jiskoot W (2011) Strategies for the assessment of protein aggregates in pharmaceutical biotech product development. Pharm Res 28(4):920–933. doi:10.1007/s11095-010-0297-1

    Article  Google Scholar 

  27. Shelke NB, Kadam R, Tyagi P, Rao VR, Kompella UB (2011) Intravitreal poly(l-lactide) microparticles sustain retinal and choroidal delivery of TG-0054, a hydrophilic drug intended for neovascular diseases. Drug Deliv Transl Res 1(1):76–90. doi:10.1007/s13346-010-0009-8

    Article  PubMed  CAS  Google Scholar 

  28. ICH Q1A (R2) (2003) Guidance (International Conference on Harmonisation). Stability testing of new drug substances and products

    Google Scholar 

  29. McCrackin FL (1987) Relationship of intrinsic viscosity of polymer solutions to molecular weight. Polymer 28(11):1847–1850

    Article  CAS  Google Scholar 

  30. Wang N, Wu XS, Lujan-Upton H, Donahue E, Siddiqui A (1997) Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid oligomers: I synthesis and characterization. J Biomater Sci Polym Ed 8(12):905–917

    Article  PubMed  CAS  Google Scholar 

  31. Dawes GJ, Fratila-Apachitei LE, Necula BS, Apachitei I, Witkamp GJ, Duszczyk J (2010) Release of PLGA-encapsulated dexamethasone from microsphere loaded porous surfaces. J Mater Sci Mater Med 21(1):215–221. doi:10.1007/s10856-009-3846-6

    Article  PubMed  CAS  Google Scholar 

  32. Mittal G, Sahana DK, Bhardwaj V, Ravi Kumar MN (2007) Estradiol loaded PLGA nanoparticles for oral administration: effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo. J Control Release 119(1):77–85. doi:10.1016/j.jconrel.2007.01.016

    Article  PubMed  CAS  Google Scholar 

  33. Wischke C, Schwendeman SP (2008) Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles. Int J Pharm 364(2):298–327. doi:10.1016/j.ijpharm.2008.04.042

    Article  PubMed  CAS  Google Scholar 

  34. Kenley RA, Maryann Ott Lee T, Randolph Mahoney II, Sanders LM (1987) Poly(lactide-co-glycolide) decomposition kinetics in vivo and in vitro. Macromolecules 20(10):2398–2403

    Article  CAS  Google Scholar 

  35. Wang N, Wu XS (1997) Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid oligomers: Part II Biodegradation and drug delivery application. J Biomater Sci Polym Ed 9(1):75–87

    Article  PubMed  CAS  Google Scholar 

  36. Park TG (1995) Degradation of poly(lactic-co-glycolic acid) microspheres: effect of copolymer composition. Biomaterials 16(15):1123–1130

    Article  PubMed  CAS  Google Scholar 

  37. Jalil R, Nixon JR (1990) Microencapsulation using poly (l-lactic acid) III: effect of polymer molecular weight on the microcapsule properties. J Microencapsul 7(1):41–52. doi:10.3109/02652049009028422

    Article  PubMed  CAS  Google Scholar 

  38. Beck LR, Pope VZ, Flowers CE Jr, Cowsar DR, Tice TR, Lewis DH, Dunn RL, Moore AB, Gilley RM (1983) Poly(dl-lactide-co-glycolide)/norethisterone microcapsules: an injectable biodegradable contraceptive. Biol Reprod 28(1):186–195

    Article  PubMed  CAS  Google Scholar 

  39. Braunecker J, Baba M, Milroy GE, Cameron RE (2004) The effects of molecular weight and porosity on the degradation and drug release from polyglycolide. Int J Pharm 282(1–2):19–34. doi:10.1016/j.ijpharm.2003.08.020

    Article  PubMed  CAS  Google Scholar 

  40. Makadia HK, Siegel SJ (2011) Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers 3(3):1377–1397. doi:10.3390/polym3031377

    Article  PubMed  CAS  Google Scholar 

  41. Vert M, Mauduit J, Li S (1994) Biodegradation of PLA/GA polymers: increasing complexity. Biomaterials 15(15):1209–1213

    Article  PubMed  CAS  Google Scholar 

  42. Yandrapu S, Kompella UB (2013) Development of sustained-release microspheres for the delivery of SAR 1118, an LFA-1 antagonist intended for the treatment of vascular complications of the eye. J Ocul Pharmacol Ther 29(2):236–248. doi:10.1089/jop.2012.0210

    Article  PubMed  CAS  Google Scholar 

  43. Tracy MA, Ward KL, Firouzabadian L, Wang Y, Dong N, Qian R, Zhang Y (1999) Factors affecting the degradation rate of poly(lactide-co-glycolide) microspheres in vivo and in vitro. Biomaterials 20(11):1057–1062

    Article  PubMed  CAS  Google Scholar 

  44. Houchin ML, Topp EM (2008) Chemical degradation of peptides and proteins in PLGA: a review of reactions and mechanisms. J Pharm Sci 97(7):2395–2404. doi:10.1002/jps.21176

    Article  PubMed  CAS  Google Scholar 

  45. Chu CC (1981) The in-vitro degradation of poly(glycolic acid) sutures—effect of pH. J Biomed Mater Res 15(6):795–804. doi:10.1002/jbm.820150604

    Article  PubMed  CAS  Google Scholar 

  46. Dunne M, Corrigan I, Ramtoola Z (2000) Influence of particle size and dissolution conditions on the degradation properties of polylactide-co-glycolide particles. Biomaterials 21(16):1659–1668

    Article  PubMed  CAS  Google Scholar 

  47. Jain A, Jain SK (2013) Formulation and optimization of temozolomide nanoparticles by 3 factor 2 level factorial design. Biomatter 3(2)

    Google Scholar 

  48. Julienne MC, Alonso MJ, Gomez Amoza JL, Benoit JP (1992) Preparation of poly(dl lactide/glycolide) nanoparticles of controlled particle size distribution: application of experimental designs. Drug Dev Ind Pharm 18(10):1063–1077. doi:10.3109/03639049209069315

    Article  CAS  Google Scholar 

  49. Gomez-Gaete C, Bustos GL, Godoy RR, Saez CK, Novoa GP, Fernandez EM, Tsapis N, Fattal E (2013) Successful factorial design for the optimization of methylprednisolone encapsulation in biodegradable nanoparticles. Drug Dev Ind Pharm 39(2):310–320. doi:10.3109/03639045.2012.676049

    Article  PubMed  CAS  Google Scholar 

  50. Lalani J, Rathi M, Lalan M, Misra A (2013) Protein functionalized tramadol-loaded PLGA nanoparticles: preparation, optimization, stability and pharmacodynamic studies. Drug Dev Ind Pharm 39(6):854–864. doi:10.3109/03639045.2012.684390

    Article  PubMed  CAS  Google Scholar 

  51. Zhou YZ, Alany RG, Chuang V, Wen J (2013) Optimization of PLGA nanoparticles formulation containing l-DOPA by applying the central composite design. Drug Dev Ind Pharm 39(2):321–330. doi:10.3109/03639045.2012.681054

    Article  PubMed  CAS  Google Scholar 

  52. ICH Q3C (R4) (2003) Guidance (International Conference on Harmonisation). Impurities: Guideline for Residual Solvents

    Google Scholar 

  53. Abdelwahed W, Degobert G, Stainmesse S, Fessi H (2006) Freeze-drying of nanoparticles: formulation, process and storage considerations. Adv Drug Deliv Rev 58(15):1688–1713. doi:10.1016/j.addr.2006.09.017

    Article  PubMed  CAS  Google Scholar 

  54. Luan X, Skupin M, Siepmann J, Bodmeier R (2006) Key parameters affecting the initial release (burst) and encapsulation efficiency of peptide-containing poly(lactide-co-glycolide) microparticles. Int J Pharm 324(2):168–175. doi:10.1016/j.ijpharm.2006.06.004

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by the NIH grant EY018940. The authors are thankful to lab members including Puneet Tyagi, Shelley Durazo, Ruchit Trivedi, and Dr. Jiban Jyoti Panda and past lab member Dr. Sarath Yandrapu for helpful discussions during the preparation of this chapter.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this protocol

Cite this protocol

Kulkarni, S.S., Kompella, U.B. (2013). Nanoparticles for Drug and Gene Delivery in Treating Diseases of the Eye. In: Gilger, B. (eds) Ocular Pharmacology and Toxicology. Methods in Pharmacology and Toxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/7653_2013_11

Download citation

  • DOI: https://doi.org/10.1007/7653_2013_11

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-744-0

  • Online ISBN: 978-1-62703-745-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics