Optimization of Polycaprolactone Based Hydrogel for Sustained drug Delivery to the Posterior Segment of Eye

Abstract

Purpose: : To optimize release profile of prednisolone and ganciclovir model drugs from polycaprolactone based triblock polymer employed in the treatment of posterior segment diseases.

Methods: : Triblock polymer was synthesized by ring opening polymerization by utilizing monomethoxypolyethylene glycol (MPEG) as an initiator. MPEG was dissolved in anhydrous toluene followed by distillation to remove residual moisture. Different ratios of MPEG and e-caprolactone, ranging from 1.0 to 4.0 were taken and stannous octoate was used as catalyst. Polymer was filtered and dried for 24 hr in vacuum at room temperature. MPEG-PCL diblock polymer was then coupled with hexamethylene disocynate and the mixture was stirred for 12 hr at 60⁰C. Polymer was purified by precipitation in a similar method used for diblock polymer and characterized by ¹H NMR and Gel Permeation Chromatography. Sol-Gel transition study was performed using test tube inversion method. Release study was performed at pH 7.4 and 37⁰C utilizing two model drugs used in the treatment of posterior segment diseases - one hydrophobic (prednisolone) and one hydrophilic (ganciclovir). Different concentrations of polycaprolactone were used as additive to optimize gelling as well as release behavior from the polymer.

Results: : Sol-gel transition study shows that 15 -20 wt % of polymer aqueous solution gels at 37⁰C depending upon the molecular weight ranging from 2000-5000 Da. Release study shows that release of drug depends upon the molecular weight and hydrophobic component of polymer. However release of hydrophobic drug from triblock polymer was sustained for three weeks but release of hydrophilic drug was over within one week period. Further addition of polycaprolactone as additive increased the gelling efficiency and enhances the sustained release profile of both model drugs.

Conclusions: : Addition of polycaprolactone, as additive in hydrogel based drug delivery will be a promising strategy in designing sustained drug delivery system for posterior segment of eye.

Keywords: drug toxicity/drug effects • retina • retinitis