title: Optimization of subconjunctival biodegradable microfilms for sustained drug delivery to the anterior segment in a small animal model.
abstract: OBJECTIVE
  We evaluated a biodegradable, sustained-release, prednisolone acetate (PA)-loaded poly[d,l-lactide-co-ε-caprolactone] (PLC) drug delivery system on its biocompatibility, feasibility and release characteristics in vitro and in vivo.
  
  
  METHODS
  Blank and 40% PA-loaded PLC microfilms with a diameter of 2 mm were fabricated, and the degradation and drug release profiles of the microfilms were characterized in vitro and in vivo. The microfilms were implanted into the subconjunctival space of Lewis rats (n = 48). All eyes were assessed clinically using slit-lamp biomicroscopy, and graded with Hackett-McDonald ocular scoring system and anterior segment optical coherence tomography. Histologic and immunohistochemical analyses were performed comparing blank and PA-loaded microfilm groups. PA concentrations in the aqueous humor were determined by HPLC.
  
  
  RESULTS
  Subconjunctivally-implanted PLC microfilms were able to deliver PA in a sustained manner over 3 months, with a steady rate of 0.002 mg/d in vivo. Eyes with either blank or PA-loaded implanted microfilms showed a very minimal inflammatory response at the insertion sites and mild degree of collagen encapsulation around the microfilms, with significantly less CD11c cells at 2 and 4 weeks (P = 0.001 and P = 0.002), and collagen formation at 2 weeks (P = 0.001) in the PA-loaded microfilm group. Anterior chamber PA levels were achieved, with concentrations at 76.7 ± 5.9, 70.3 ± 2.3, and 42.7 ± 4.1 ng/mL at 2, 4, and 12 weeks, respectively.
  
  
  CONCLUSIONS
  PA-loaded PLC microfilms display good biocompatibility, feasibility, and desirable sustained drug release profiles, and have the potential to exhibit antifibrotic and anti-inflammatory effects. This device is applicable to use in small animal models of anterior segment inflammation.
authors.affiliation: Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute, Singapore.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.forename: Nyein Chan
authors.initials: NC
authors.lastname: Lwin
authors.forename: Tina T
authors.initials: TT
authors.lastname: Wong
authors.forename: Subbu S
authors.initials: SS
authors.lastname: Venkatraman
authors.forename: Jodhbir S
authors.initials: JS
authors.lastname: Mehta
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D003228:Conjunctiva; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004337:Drug Carriers; D004343:Drug Implants; D005260:Female; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants