Preparation, characterization and drug release properties of 5-(p-carboxyphenoxy) valeric anhydride microspheres loaded with nimodipine.

Abstract

Nimodipine (NMP), a poorly water-soluble small-molecule agent, demonstrates notable therapeutic limitations in addressing cerebral vasospasm secondary to subarachnoid hemorrhage (SAH). Owing to its inherent physicochemical properties characterized by low oral bioavailability, rapid elimination half-life, and extensive first-pass metabolism, conventional formulations necessitate frequent dosing regimens to sustain therapeutic plasma concentrations. These pharmacological challenges collectively result in suboptimal patient adherence, marked plasma concentration fluctuations, and recurrent vascular irritation. To overcome these pharmacological constraints, this investigation engineered a novel drug-loaded microsphere system utilizing poly(5-(p-carboxyphenoxy) valeric anhydride (Poly(CPV)) as a biodegradable matrix material. The sustained-release microspheres were fabricated via microfluidic technology to systematically address the clinical challenges associated with frequent dosing regimens. The optimized microspheres exhibited a drug loading capacity of 5.59%, an encapsulation efficiency of 70.22%, and a uniform particle size distribution (43.98 ± 4.29 μm). In vitro release studies demonstrated sustained drug release over 14 days. Pharmacokinetic evaluation in rats revealed that the NMP-loaded microspheres maintained relative stable plasma drug concentrations for approximately 10 days. Biocompatibility assessments, including histocompatibility tests and in vitro cytotoxicity assays, confirmed the excellent biocompatibility of the Poly(CPV) microsphere. These findings suggest that Poly(CPV)-based microspheres prepared by microfluidics represent a promising drug delivery platform for poorly soluble small-molecule pharmaceuticals, offering controlled release characteristics and improved therapeutic outcomes.