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Yan Peng, Yu-Chi Liu, Nyein Chan Lwin, Subbu S Venkatraman, Tina Wong, Jodhbir Mehta; Evaluation of drug delivery and biocompatibility of biodegradable microfilms in the anterior segment of the rat model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1092.
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© ARVO (1962-2015); The Authors (2016-present)
To develop a biodegradable, sustained-release, prednisolone acetate (PA)-loaded poly [d,l-lactide-co-ε-caprolactone] (PLC) drug delivery system and to evaluate its biocompatibility, feasibility and release characteristics both in vitro and in vivo.
Blank and 40% PA-loaded PLC microfilms with thickness of 100µm and diameter of 2mm were developed and tested in vitro and in vivo. The degradation and drug release profiles of the microfilms were evaluated in the in vitro and in vivo experiments. We further implanted the microfilms to the subconjunctival space of the rats (n=51). All eyes were monitored using slit lamp bio-microscopy with Hackett McDonald ocular scoring system and anterior segment optical coherence tomography. Histological studies with Hematoxylin-Eosin, Picrosirus red staining and immunohistochemistry analysis were performed to evaluate and compare the presence of inflammatory and fibrotic reaction in blank and PA-loaded microfilm groups. PA concentrations in the aqueous humor were determined by high-performance liquid chromatography (HPLC).
Subconjunctivally-implanted PA-loaded PLC microfilms were able to deliver prednisolone acetate in a sustained manner over 3 months, with a steady rate of 0.002mg/day in vivo. Eyes with either blank or PA-loaded implanted microfilms showed very minimal inflammatory response at the insertion sites and mild degree of collagen encapsulation around the microfilms, with significantly less CD11c cells at 2 weeks (P = 0.001) and collagen extent at 2 and 4 weeks (P = 0.001 and P = 0.002) in PA-loaded microfilm group. Desirable anterior chamber PA levels were achieved, with the concentrations at 76.67±5.86, 69.33±2.3 and 42.67±4.1 ng/ml at 2, 4 and 12 weeks, respectively.
PA-loaded PLC microfilm displays good biocompatibility, feasibility and desirable sustained drug release profiles. This device provides a promising alternative with great potential application in the treatments of ocular anterior segment diseases.
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