Optimization and Characterization of Brinzolamide Loaded Biodegradable, Amphiphilic Poly-caprolactone-Polyethylene Glycol-Poly-Caprolactone (۵۰۰۰-۱۰۰۰-۵۰۰۰) Tri-block Co-polymeric Carriers as Long-Acting Intravitreal Drug Delivery Vehicle for Glaucoma Therapy

The aim of this study was to formulate brinzolamide microparticles using a synthesized novel, biodegradable, amphiphilic and tri-block poly-caprolactone- polyethylene glycol-poly-caprolactone (۵۰۰۰–۱۰۰۰-۱۰۰۰) co-polymer by solvent evaporation technique. Optimized the microparticles preparation was done using a ۳۲-factorial design, with the amount of co-polymer (X۱) and stirring speed (X۲) as independent variables and assessed the responses of the particle sizes (Y۱), encapsulation efficiency (Y۲), and burst release (Y۳). Other in vitro characterization tests like viscosity, pH, osmolarity, reconstitution time, water content by Karl Fisher titration, release kinetics, FTIR spectroscopy, differential scanning calorimetry, X-ray diffraction, gas chromatography, thermogravimetric analysis, ۱H-NMR, and ۱۳C-NMR Spectroscopy were performed. Encapsulation efficiency reached ۶۸.۳۲±۱.۶۳% under optimal conditions (X۱ = ۱۰۱ mg, X۲ = ۷۲۹ RPM), with a ۶۶.۷۷±۳.۴۳ μm size range and a burst release rate of ۱۲.۸۹±۸.۳۸%. In phosphate-buffer saline at pH ۷.۴, the in vitro drug release was sustained up to ۱۰ days with zero order kinetics. All results were satisfactory and the hydroxyl end cap and ۹۱:۰۹ molar ratio of caprolcatone and ethylene glycol for formed microparticles were confirmed by ۱H-NMR and ۱۳ C-NMR.  In summary the developed novel, biodegradable, and injectable micro-particles have the potential for long-acting brinzolamide release for intra-vitreal drug delivery.

کلیدواژه ها:

Tri-block co-polymeric carriers ، Intra-vitreal drug delivery ، Glaucoma therapy ، in vitro drug release ، Synthesis