Development, optimization, in-vitro, and in-vivo evaluation of chitosan-inlayed nano-spanlastics encompassing lercanidipine HCl for enhancement of bioavailability

Abstract

Low bioavailability is a major challenge in the development of new pharmacological formulations for oral administration. The vasoselective calcium channel blocker lercanidipine HCl (LER) has a bioavailability of only 10 % owing to its first-pass metabolism and poor solubility. To address the bioavailability issue, the intranasal route was frequently adopted for medications. Therefore, this research's objective was to develop an intranasal chitosan coated nanospanlastics-loaded with LER to improve its bioavailability and diffusion. LER spanlastic nanovesicles (LER-SNVs) were developed and optimized using a factorial design employing the thin-film hydration technique. The researchers studied the influence of the type of Span surfactant, type of edge activator (EA), and ratio of Span to EA on encapsulation efficiency (EE%); the particle size of the spanlastic; the percentage of drug release; and the cumulative LER diffused per unit area after 24 h, or Q24 (g/cm2). Following optimal formulation development, chitosan was utilized to modify its surface. Subsequently, the pharmacokinetics and biocompatibility of optimal chitosan-coated preparation were ascertained in rats. The results of the SNV analysis showed that their mean size was below 400 nm and that the EE% reached 94 %. In contrast to the LER dispersion, the designed LER-SNVs boosted drug transmucosal permeation. The pharmacokinetic studies showed a fourfold (p < 0.05) increase in the relative bioavailability of LER after the nasal delivery of LER-loaded surface-modified SNVs compared with an oral LER dispersion. Optimal CS-coated formulation was found biocompatible with studied animals. In conclusion, the use of SNVs for the nasal delivery of LER has shown promise, and the results could lead to better management of hypertension.