Physicochemical Requirements for Polymers and Polymer-Based Nanomaterial for Ophthalmic Drug Delivery

  • Sheeba Varghese GuptaEmail author


Polymers used for constructing ophthalmic nanodelivery systems play a crucial role in determining the drug entrapment capacity, biodegradation, and residence time of the nanoparticles. Polymers used for ophthalmic nanodelivery systems are biodegradable; the biodegradation may be enzymatically or chemically mediated. The physicochemical properties of the polymers such as molecular weight, hydrophobicity/hydrophilicity, polymer/copolymer composition, crystallinity, and glass transition temperature affect particle size, entrapment efficiency, adsorption/absorption pattern, degradation kinetics, and mechanical strength of the nanoparticles. PLGA is the most widely used polymer for ophthalmic delivery because of its biodegradability and flexibility in alteration of the physicochemical properties by altering the copolymer composition. Physicochemical properties of a polymer can be altered by chemical modifications. In-depth understanding of the physicochemical properties of the polymers is important to design a nanodelivery system with optimum drug encapsulation, degradation, and residence time.


Physicochemical properties Molecular weight Crystallinity Glass transition temperature Biodegradation PLGA 


  1. 1.
    Tamboli V, Mishra GP, Mitra AK (2012) Biodegradable polymers for ocular drug delivery. In: Mitra AK (ed) Advances in ocular drug delivery. Research Signpost, Trivandrum, pp 65–86Google Scholar
  2. 2.
    Ahmed F, Pakunlu RI, Brannan A, Bates F, Minko T, Discher DE (2006) Biodegradable polymersomes loaded with both paclitaxel and doxorubicin permeate and shrink tumors, inducing apoptosis in proportion to accumulated drug. J Control Release 116(2):150–158, Epub 2006/09/01CrossRefPubMedGoogle Scholar
  3. 3.
    Nagarwal RC, Kant S, Singh PN, Maiti P, Pandit JK (2009) Polymeric nanoparticulate system: a potential approach for ocular drug delivery. J Control Release 136(1):2–13, Epub 2009/04/01CrossRefPubMedGoogle Scholar
  4. 4.
    Sahoo SK, Dilnawaz F, Krishnakumar S (2008) Nanotechnology in ocular drug delivery. Drug Discov Today 13(3–4):144–151, Epub 2008/02/16CrossRefPubMedGoogle Scholar
  5. 5.
    Mudgil M, Gupta N, Nagpal M, Pawar P (2012) Nanotechnology: a new approach for ocular drug delivery system. Int J Pharm Sci 4(2):105–112Google Scholar
  6. 6.
    Makadia HK, Siegel SJ (2011) Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers 3(3):1377–1397, Epub 2012/05/12CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Di Colo G, Zambito Y, Burgalassi S, Nardini I, Saettone MF (2004) Effect of chitosan and of N-carboxymethylchitosan on intraocular penetration of topically applied ofloxacin. Int J Pharm 273(1–2):37–44CrossRefPubMedGoogle Scholar
  8. 8.
    Nagarwal RC, Kumar R, Pandit JK (2012) 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 47(4):678–685, Epub 2012/08/28CrossRefPubMedGoogle Scholar
  9. 9.
    Mahmoud AA, El-Feky GS, Kamel R, Awad GE (2011) Chitosan/sulfobutylether-beta-cyclodextrin nanoparticles as a potential approach for ocular drug delivery. Int J Pharm 413(1–2):229–236, Epub 2011/05/05CrossRefPubMedGoogle Scholar
  10. 10.
    Joshi SA, Chavhan SS, Sawant KK (2010) Rivastigmine-loaded PLGA and PBCA nanoparticles: preparation, optimization, characterization, in vitro and pharmacodynamic studies. Eur J Pharm Biopharm 76(2):189–199, Epub 2010/07/20CrossRefPubMedGoogle Scholar
  11. 11.
    Katti DS, Lakshmi S, Langer R, Laurencin CT (2002) Toxicity, biodegradation and elimination of polyanhydrides. Adv Drug Deliv Rev 54(7):933–961, Epub 2002/10/18CrossRefPubMedGoogle Scholar
  12. 12.
    Pak J, Lakes RS (2007) Biomaterials an introduction, 3rd edn. Springer, New YorkGoogle Scholar
  13. 13.
    Azevedo HS, Reis RL (2004) Understanding the enzymatic degradation of biodegradable polymers and strategies to control their degradation rate. In: Reis RL (ed) Biodegradable systems in tissue engineering and regenerative medicine. CRC Press, Boca Raton, pp 177–201Google Scholar
  14. 14.
    Nordtveit RJ, Vårum KM, Smidsrød O (1996) Degradation of partially N-acetylated chitosans with hen egg white and human lysozyme. Carbohydr Polym 29:163–167CrossRefGoogle Scholar
  15. 15.
    Tomihata K, Ikada Y (1997) In vitro and in vivo degradation of films of chitin and its deacetylated derivatives. Biomaterials 18(7):567–575, Epub 1997/04/01CrossRefPubMedGoogle Scholar
  16. 16.
    Mi FL, Tan YC, Liang HC, Huang RN, Sung HW (2001) In vitro evaluation of a chitosan membrane cross-linked with genipin. J Biomater Sci Polym Ed 12(8):835–850, Epub 2001/11/23CrossRefPubMedGoogle Scholar
  17. 17.
    Woodruff CW, Peck GE, Banker GS (1972) Dissolution of alkyl vinyl ether-maleic anhydride copolymers and ester derivatives. J Pharm Sci 61(12):1912–1916, Epub 1972/12/01CrossRefPubMedGoogle Scholar
  18. 18.
    Kimura H, Ogura Y (2001) Biodegradable polymers for ocular drug delivery. Ophthalmologica 215(3):143–155, Epub 2001/05/08CrossRefPubMedGoogle Scholar
  19. 19.
    Matsumoto J, Nakada Y, Sakurai K, Nakamura T, Takahashi Y (1999) Preparation of nanoparticles consisted of poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) and their evaluation in vitro. Int J Pharm 185(1):93–101, Epub 1999/07/30CrossRefPubMedGoogle Scholar
  20. 20.
    Yang H-C, Hon M-H (2009) The effect of the molecular weight of chitosan nanoparticles and its application on drug delivery. Microchem J 92(1):87–91CrossRefGoogle Scholar
  21. 21.
    Mehta RC, Thanoo BC, Deluca PP (1996) Peptide containing microspheres from low molecular weight and hydrophilic poly(d, l-lactide-co-glycolide). J Control Release 41(3):249–257CrossRefGoogle Scholar
  22. 22.
    Zambaux MF, Bonneaux F, Gref R, Maincent P, Dellacherie E, Alonso MJ et al (1998) Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method. J Control Release 50(1–3):31–40CrossRefPubMedGoogle Scholar
  23. 23.
    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, Epub 2007/03/14CrossRefPubMedGoogle Scholar
  24. 24.
    Araújo J, Vega E, Lopes C, Egea MA, Garcia ML, Souto EB (2009) Effect of polymer viscosity on physicochemical properties and ocular tolerance of FB-loaded PLGA nanospheres. Colloids Surf B Biointerfaces 72(1):48–56CrossRefPubMedGoogle Scholar
  25. 25.
    Mikos AG, Peppas NA (1986) Systems for controlled release of drugs v. bioadhesive systems. STP Pharm 2:705–716Google Scholar
  26. 26.
    Dash TK, Konkimalla VB (2012) Poly-small je, Ukrainian-caprolactone based formulations for drug delivery and tissue engineering: a review. J Control Release 158(1):15–33, Epub 2011/10/04CrossRefPubMedGoogle Scholar
  27. 27.
    Bilensoy E, Sarisozen C, Esendagli G, Dogan AL, Aktas Y, Sen M et al (2009) Intravesical cationic nanoparticles of chitosan and polycaprolactone for the delivery of Mitomycin C to bladder tumors. Int J Pharm 371(1–2):170–176, Epub 2009/01/13CrossRefPubMedGoogle Scholar
  28. 28.
    Park TG (1995) Degradation of poly(lactic-co-glycolic acid) microspheres: effect of copolymer composition. Biomaterials 16(15):1123–1130, Epub 1995/10/01CrossRefPubMedGoogle Scholar
  29. 29.
    Panyam J, Williams D, Dash A, Leslie-Pelecky D, Labhasetwar V (2004) Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles. J Pharm Sci 93(7):1804–1814, Epub 2004/06/04CrossRefPubMedGoogle Scholar
  30. 30.
    Sonam HC, Arora V, Koli K, Kumar V (2013) Effect of physicochemical properties of biodegradable polymers on nano drug delivery. Polymer Rev 53(4):546–567CrossRefGoogle Scholar
  31. 31.
    Youan BB, Benoit MA, Baras B, Gillard J (1999) Protein-loaded poly(epsilon-caprolactone) microparticles. I. Optimization of the preparation by (water-in-oil)-in water emulsion solvent evaporation. J Microencapsul 16(5):587–599, Epub 1999/09/28CrossRefPubMedGoogle Scholar
  32. 32.
    Kumar M (2000) A review of chitin and chitosan applications. React Funct Polym 46:1–27CrossRefGoogle Scholar
  33. 33.
    Sabnis S, Block LH (2000) Chitosan as an enabling excipient for drug delivery systems. I. Molecular modifications. Int J Biol Macromol 27(3):181–186, Epub 2000/06/01CrossRefPubMedGoogle Scholar
  34. 34.
    Benesch J, Tengvall P (2002) Blood protein adsorption onto chitosan. Biomaterials 23(12):2561–2568, Epub 2002/05/30CrossRefPubMedGoogle Scholar
  35. 35.
    Chatelet C, Damour O, Domard A (2001) Influence of the degree of acetylation on some biological properties of chitosan films. Biomaterials 22(3):261–268, Epub 2001/02/24CrossRefPubMedGoogle Scholar
  36. 36.
    Ottoy MHV, Varum KM, Smidsrod O (1996) Compositional heterogeneity of heterogeneously deacetylated chitosans. Carbohydr Polym 29:17–24CrossRefGoogle Scholar
  37. 37.
    Anthonsen MWV, Varum KM, Smidsrod O (1993) Solution properties of chitosans-confirmation and chain stiffness of chitosans with different degrees. Carbohydr Polym 22:193–201CrossRefGoogle Scholar
  38. 38.
    Shi C, Zhu Y, Ran X, Wang M, Su Y, Cheng T (2006) Therapeutic potential of chitosan and its derivatives in regenerative medicine. J Surg Res 133(2):185–192, Epub 2006/02/07CrossRefPubMedGoogle Scholar
  39. 39.
    Badawi AA, El-Laithy HM, El Qidra RK, El Mofty H, El dally M (2008) Chitosan based nanocarriers for indomethacin ocular delivery. Arch Pharm Res 31(8):1040–1049, Epub 2008/09/13CrossRefPubMedGoogle Scholar
  40. 40.
    De Campos AM, Sanchez A, Alonso MJ (2001) Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A. Int J Pharm 224(1–2):159–168, Epub 2001/07/27CrossRefPubMedGoogle Scholar
  41. 41.
    de Campos AM, Diebold Y, Carvalho EL, Sanchez A, Alonso MJ (2004) Chitosan nanoparticles as new ocular drug delivery systems: in vitro stability, in vivo fate, and cellular toxicity. Pharm Res 21(5):803–810, Epub 2004/06/08CrossRefPubMedGoogle Scholar
  42. 42.
    De Campos AM, Sanchez A, Gref R, Calvo P, Alonso MJ (2003) The effect of a PEG versus a chitosan coating on the interaction of drug colloidal carriers with the ocular mucosa. Eur J Pharm Sci 20(1):73–81, Epub 2003/09/19CrossRefPubMedGoogle Scholar
  43. 43.
    Gaspard S, Oujja M, Abrusci C, Catalina F, Lazare S, Desvergne JP, Castillejo M (2008) Laser induced foaming and chemical modifications of gelatin films. J Photochem Photobiol A 193:187–192CrossRefGoogle Scholar
  44. 44.
    Young S, Wong M, Tabata Y, Mikos AG (2005) Gelatin as a delivery vehicle for the controlled release of bioactive molecules. J Control Release 109(1–3):256–274, Epub 2005/11/04CrossRefPubMedGoogle Scholar
  45. 45.
    Natu MV, Sardinha JP, Correia IJ, Gil MH (2007) Controlled release gelatin hydrogels and lyophilisates with potential application as ocular inserts. Biomed Mater 2(4):241–249, Epub 2008/05/07CrossRefPubMedGoogle Scholar
  46. 46.
    Hong Y, Chirila TV, Vijayasekaran S, Shen W, Lou X, Dalton PD (1998) Biodegradation in vitro and retention in the rabbit eye of crosslinked poly(1-vinyl-2-pyrrolidinone) hydrogel as a vitreous substitute. J Biomed Mater Res 39(4):650–659, Epub 1998/03/10CrossRefPubMedGoogle Scholar
  47. 47.
    Colthurst MJ, Williams RL, Hiscott PS, Grierson I (2000) Biomaterials used in the posterior segment of the eye. Biomaterials 21(7):649–665, Epub 2000/03/11CrossRefPubMedGoogle Scholar
  48. 48.
    Niu G, Yang Y, Zhang H, Yang J, Song L, Kashima M et al (2009) Synthesis and characterization of acrylamide/N-vinylpyrrolidone copolymer with pendent thiol groups for ophthalmic applications. Acta Biomater 5(4):1056–1063, Epub 2008/12/17CrossRefPubMedGoogle Scholar
  49. 49.
    Hacker MC, Haesslein A, Ueda H, Foster WJ, Garcia CA, Ammon DM et al (2009) Biodegradable fumarate-based drug-delivery systems for ophthalmic applications. J Biomed Mater Res A 88(4):976–989, Epub 2008/04/04CrossRefPubMedGoogle Scholar
  50. 50.
    Yasukawa T, Ogura Y, Kimura H, Sakurai E, Tabata Y (2006) Drug delivery from ocular implants. Expert Opin Drug Deliv 3(2):261–273, Epub 2006/03/02CrossRefPubMedGoogle Scholar
  51. 51.
    Vega E, Gamisans F, Garcia ML, Chauvet A, Lacoulonche F, Egea MA (2008) PLGA nanospheres for the ocular delivery of flurbiprofen: drug release and interactions. J Pharm Sci 97(12):5306–5317, Epub 2008/04/22CrossRefPubMedGoogle Scholar
  52. 52.
    Zentner GM, Rathi R, Shih C, McRea JC, Seo MH, Oh H et al (2001) Biodegradable block copolymers for delivery of proteins and water-insoluble drugs. J Control Release 72(1–3):203–215, Epub 2001/06/08CrossRefPubMedGoogle Scholar
  53. 53.
    Duvvuri S, Janoria KG, Mitra AK (2005) Development of a novel formulation containing poly(d, l-lactide-co-glycolide) microspheres dispersed in PLGA-PEG-PLGA gel for sustained delivery of ganciclovir. J Control Release 108(2–3):282–293, Epub 2005/10/19CrossRefPubMedGoogle Scholar
  54. 54.
    Duvvuri S, Janoria KG, Pal D, Mitra AK (2007) Controlled delivery of ganciclovir to the retina with drug-loaded Poly(d, L-lactide-co-glycolide) (PLGA) microspheres dispersed in PLGA-PEG-PLGA Gel: a novel intravitreal delivery system for the treatment of cytomegalovirus retinitis. J Ocul Pharm Ther 23(3):264–274, Epub 2007/06/27CrossRefGoogle Scholar
  55. 55.
    Sinha VR, Bansal K, Kaushik R, Kumria R, Trehan A (2004) Poly-epsilon-caprolactone microspheres and nanospheres: an overview. Int J Pharm 278(1):1–23, Epub 2004/05/26CrossRefPubMedGoogle Scholar
  56. 56.
    Fialho SL, Behar-Cohen F, Silva-Cunha A (2008) Dexamethasone-loaded poly(epsilon-caprolactone) intravitreal implants: a pilot study. Eur J Pharm Biopharm 68(3):637–646, Epub 2007/09/14CrossRefPubMedGoogle Scholar
  57. 57.
    Yin H, Gong C, Shi S, Liu X, Wei Y, Qian Z (2010) Toxicity evaluation of biodegradable and thermosensitive PEG-PCL-PEG hydrogel as a potential in situ sustained ophthalmic drug delivery system. J Biomed Mater Res B Appl Biomater 92(1):129–137, Epub 2009/10/06CrossRefPubMedGoogle Scholar
  58. 58.
    Adjadj E, Roy S, Zimmermann C, Shaarawy T, Flammer J, Mermoud A et al (2006) Dosage et cinetique de liberation de mitomycine C d’un implant de collagene utilise comme moyen d’administration lors d’une chirurgie filtrante chez le lapin. J Fr Ophtalmol 29(9):1042–1046, Epub 2006/11/23. Dosage and kinetics of MMC release of a collagen implant used as a delivery device in glaucoma surgery in the rabbit eyeCrossRefPubMedGoogle Scholar
  59. 59.
    Lai J-Y, Hsieh A-C (2012) A gelatin-g-poly(N-isopropylacrylamide) biodegradable in situ gelling delivery system for the intracameral administration of pilocarpine. Biomaterials 33(7):2372–2387CrossRefPubMedGoogle Scholar
  60. 60.
    Bonferoni MC, Chetoni P, Giunchedi P, Rossi S, Ferrari F, Burgalassi S et al (2004) Carrageenan-gelatin mucoadhesive systems for ion-exchange based ophthalmic delivery: in vitro and preliminary in vivo studies. Eur J Pharm Biopharm 57(3):465–472, Epub 2004/04/20CrossRefPubMedGoogle Scholar
  61. 61.
    Chhonker YS, Prasad YD, Chandasana H, Vishvkarma A, Mitra K, Shukla PK et al (2014) Amphotericin-B entrapped lecithin/chitosan nanoparticles for prolonged ocular application. Int J Biol Macromol 72C:1451–1458, Epub 2014/12/03Google Scholar
  62. 62.
    Wang F, Chen L, Zhang D, Jiang S, Shi K, Huang Y et al (2014) Methazolamide-loaded solid lipid nanoparticles modified with low-molecular weight chitosan for the treatment of glaucoma: vitro and vivo study. J Drug Target 22(9):849–858, Epub 2014/07/22CrossRefPubMedGoogle Scholar
  63. 63.
    Yasukawa T, Kimura H, Kunou N, Miyamoto H, Honda Y, Ogura Y, Ikada Y (2000) Biodegradable scleral implant for intravitreal controlled release of ganciclovir. Graefes Arch Clin Exp Ophthalmol 238(2):186–190CrossRefPubMedGoogle Scholar
  64. 64.
    Fernandes-Cunha GM, Gouvea DR, Fulgencio GD, Rezende CM, da Silva GR, Bretas JM et al (2014) Development of a method to quantify clindamycin in vitreous humor of rabbits’ eyes by UPLC-MS/MS: application to a comparative pharmacokinetic study and in vivo ocular biocompatibility evaluation. J Pharm Biomed Anal 102:346–352, Epub 2014/12/03CrossRefPubMedGoogle Scholar
  65. 65.
    Gavini E, Chetoni P, Cossu M, Alvarez MG, Saettone MF, Giunchedi P (2004) PLGA microspheres for the ocular delivery of a peptide drug, vancomycin using emulsification/spray-drying as the preparation method: in vitro/in vivo studies. Eur J Pharm Biopharm 57(2):207–212, Epub 2004/03/17CrossRefPubMedGoogle Scholar
  66. 66.
    Meng Y, Sun S, Li J, Nan K, Lan B, Jin Y et al (2014) Sustained release of triamcinolone acetonide from an episcleral plaque of multilayered poly-ε-caprolactone matrix. Acta Biomater 10(1):126–133CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.College of PharmacyUniversity of South FloridaTampaUSA

Personalised recommendations