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Optimization, Biopharmaceutical Prof ile and Therapeutic Ef f i cacy of Pi ogl i tazone-l oaded PLGA-PEG Nanospheres as a Novel Strategy for Ocular Inflammatory Disorders

Abstract:

Purpose The main goal of this study was to encapsulate Pioglitazone (PGZ), in biodegradable polymeric nanoparticles as a new strategy for the treatment of ocular inflammatory processes. Methods To improve their biopharmaceutical profile for the treatment of ocular inflammatory disorders, nanospheres (NSs) of PGZ were formulated by factorial design with poly (lactic-co-glycolic acid) polyethylene glycol (PLGA-PEG). Interactions drug-polymer have been carried out by spectroscopic (X-ray spectroscopy, FTIR) and thermal methods (DSC). The PGZ-NSs were tested for their in vitro release profile, cytotoxicity, and ocular tolerance (HET-CAM® test); ex vivo corneal permeation, and in vivo inflammatory preven-tion and bioavailability. Results The optimized system showed a negative surface charge of −13.9 mV, an average particle size (Z<inf>av</inf>) of around 160 nm, a polydispersity index (PI) below 0.1, and a high encapsulation efficiency (EE) of around 92%. According to the DSC results, the drug was incorporated into the NSs polymeric matrix. The drug release was sustained for up to 14 h. PGZ-NSs up to 10 μg/ml exhibited no retinoblastoma cell toxicity. The ex vivo corneal and scleral permeation profiles of PGZ-NSs showed that retention and permeation through the sclera were higher than through the cornea. Ocular tolerance in vitro and in vivo demonstrated the non-irritant character of the formulation. Conclusion The in vivo anti-inflammatory efficacy of devel-oped PGZ-NSs indicates this colloidal system could constitute a new approach to prevent ocular inflammation.