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T. T. Shen, S. Garty, N. Kim, S. Kanayama, B. Ratner; Thermosensitive, Injectable, Biodegradable Polymers for Ocular Drug Delivery. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5324.
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To synthesize and characterize a biodegratable thermosensitive polymer platform using controlled radical polymerization integrating Poly(N-isopropyl acrylamide) (pNIPAAm) with predefined molecular weight and a biodegradable polyester for sustained ocular drug delivery.
Polymer samples of pre-defined molecular weight were synthesized. Controlled radical polymerization agent was synthesized and coupled to polyester forming a degradable macroinitiator. Then, NIPAAm monomer was polymerized, resulting in polymers with controlled architecture. Norfloxacin antibiotic was incorporated into pNIPAAm water solution. In vitro drug release at 37°C was measured using spectrophotometry. Cytotoxicity assays of polymers were conducted using 3T3 NIH cells. In vivo drug relaease of the pNIPAAm-antibiotic solutions was injected into the anterior chamber and the drug levels were measured over two weeks in a rabbit model.
The polymer-drug solution exhibits a rapid reversible phase transition at body temperature from liquid to solid. In vitro drug release at 37 degrees demonstrated an initial burst release within the first 48 hours, followed by continued release over two weeks. In vitro cytotoxicity was minimum. The liquid form of polymer drug solution can be injected into the anterior chamber in vivo where it solidifies and slowly biodegrades to achieve sustained drug release over two weeks. Minimal in vivo inflammation was observed.
The new biodegradable reversible, thermosensitive polymers demonstrate sustained drug release characteristics in vitro and in vivo. The delivery platform has the potential to be customized for wide range of sustained ocular drug delivery strategies. Future optimization of phase transition and drug release rates can be further developed for specific ocular drug delivery applications.
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