Long term delivery of glibenclamide from in situ forming microparticles for the treatment of ischemic stroke

Abstract

Glibenclamide, sulfonylurea receptor inhibitor, is reported to be neuroprotective in ischemic stroke by reducing cytotoxic edema, which is the primary cause of morbidity. As neurological worsening in stroke occurs from 3 to 10 days post-injury, there is a need to develop a system that would provide the release of glibenclamide for 10–15 days in a sustained manner in order to y improve the neurological functions effectively. In situ forming microparticles (ISFM) of glibenclamide was developed using PLGA 50:50 as a biodegradable polymer and by applying RSM I-Optimal design. In vitro evaluation studies were carried out for optimized formulation. In vivo pharmacological assessments and pharmacokinetics studies were performed in the Bilateral common carotid artery occlusion model (BCCAO) in Wistar rats. In vitro drug release studies showed a minimum burst release at 12 h and maximum release on 15th day. In vivo results showed a significant improvement in neurological functions, reduction in the infarct area, and hemispheric swelling in glibenclamide ISFM treated animals as compared to diseased animals. From in vitro and in vivo animal studies, it was concluded that long-acting ISFM of glibenclamide was successfully developed, which showed drug release pattern in a sustained manner for up to 15 days for preventing the neurological worsening in stroke.