title: Biocompatibility and biodegradation studies of subconjunctival implants in rabbit eyes.
abstract: Sustained ocular drug delivery is difficult to achieve. Most drugs have poor penetration due to the multiple physiological barriers of the eye and are rapidly cleared if applied topically. Biodegradable subconjunctival implants with controlled drug release may circumvent these two problems. In our study, two microfilms (poly [d,l-lactide-co-glycolide] PLGA and poly[d,l-lactide-co-caprolactone] PLC were developed and evaluated for their degradation behavior in vitro and in vivo. We also evaluated the biocompatibility of both microfilms. Eighteen eyes (9 rabbits) were surgically implanted with one type of microfilm in each eye. Serial anterior-segment optical coherence tomography (AS-OCT) scans together with serial slit-lamp microscopy allowed us to measure thickness and cross-sectional area of the microfilms. In vitro studies revealed bulk degradation kinetics for both microfilms, while in vivo studies demonstrated surface erosion kinetics. Serial slit-lamp microscopy revealed no significant inflammation or vascularization in both types of implants (mean increase in vascularity grade PLGA50/50 12±0.5% vs. PLC70/30 15±0.6%; P = 0.91) over a period of 6 months. Histology, immunohistochemistry and immuno-fluorescence also revealed no significant inflammatory reaction from either of the microfilms, which confirmed that both microfilms are biocompatible. The duration of the drug delivery can be tailored by selecting the materials, which have different degradation kinetics, to suit the desired clinical therapeutic application.
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.forename: Marcus
authors.initials: M
authors.lastname: Ang
authors.forename: Selin
authors.initials: S
authors.lastname: Foo
authors.forename: Wing Sum
authors.initials: WS
authors.lastname: Lee
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ma
authors.forename: Subbu S
authors.initials: SS
authors.lastname: Venkatraman
authors.forename: Tina T
authors.initials: TT
authors.lastname: Wong
mesh_terms: D000042:Absorption; D000818:Animals; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000601:surgery; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D005240:Feasibility Studies; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D008422:Materials Testing; D008970:Molecular Weight; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019736:Prostheses and Implants / Q000009:adverse effects*; D011817:Rabbits; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C062968:lactide-caprolactone copolymer