New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats

Abstract

Purpose: Candesartan cilexetil (CC), a prodrug of candesartan (CDT), is a class II BCS drug that suffers from poor oral bioavailability because of low aqueous solubility, P-gp efflux and first-pass metabolism. The absolute bioavailability reported for CC was only 15% and the methods to increase it remain elusive, thus the aim of our work was to prepare new CCloaded niosomes encompassing, for the first time, glycerol monooleate GMO (Peceol™), as P-gp efflux inhibitor and promoter of lymphatic transport with Span™ 60 as bioenhancer. The prepared niosomes were further coated with chitosan for augmenting the CC oral absorption. Methods: The niosomes were prepared by thin film hydration method through quality by design approach, using two levels of each of three critical process parameters (CPPs), namely, X A (the molar ratio of surfactant mixture to cholesterol) at a ratio of 1:1 or 2:1; X B (the molar ratio of Span™ 60 to Peceol™) at a ratio of 1:1 or 2:1; and X C (the drug amount) at 15 mg or 30 mg. The investigated critical quality attributes (CQAs) were entrapment efficiency percent, particle size, and polydispersity index. The optimized uncoated and chitosan coated formulations were subjected to DSC and stability study. In vitro drug release, biocompatibility with Caco-2 cells and lastly the absolute bioavailability evaluation in rats were assessed. Results: The physical properties of the optimized and stable niosomes were satisfactory. The ingredients were compatible with each other and biocompatible with Caco-2 cells. The synergistic combination of Peceol™ and Span™ 60 probably surmounted the P-gp efflux with an increase in oral absolute bioavailability of niosomes to five times that of CC suspension. Conclusion:The new niosomal formulations of CC containing Peceol™ with Span™ 60 and cholesterol either uncoated or coated with chitosan were a successful paradigm in achieving high oral absolute bioavailability and increased Caco-2 cells biocompatibility.

Spanlastic-laden in situ gel as a promising approach for ocular delivery of Levofloxacin: In-vitro characterization, microbiological assessment, corneal permeability and in-vivo study

“…There was a slight shift in the peak of Span 60 from 64 to 54 °C in both plain and medicated F5 that could be due to assembly of Span 60 into the SLs bilayers that decreased its fusion point ( El-Ridy et al, 2011 ) ( AbuElfadl et al, 2021 ). However the peaks of drug were completely disappeared in both plain and medicated thermograms which indicated a complete encapsulation of drug and its conversion to amorphous form instead of the crystalline drug form ( Mohamed et al, 2017 ) ( Zafar et al, 2022 ).…”

Cross-Linked Alginate Dialdehyde/Chitosan Hydrogel Encompassing Curcumin-Loaded Bilosomes for Enhanced Wound Healing Activity

“…The DSC thermogram of curcumin showed a sharp endothermic peak at 160.33 °C, which indicated the melting point of its crystalline form [ 45 , 102 ]. The Span ® 60 DSC thermogram revealed an endothermic peak at 59.12 °C, representing its transition temperature [ 103 , 104 ]. SDC gave an exothermic peak at 186.85 °C [ 105 ].…”

Chitosan-Coated Niosomes Loaded with Ellagic Acid Present Antiaging Activity in a Skin Cell Line

“…The results were confirmed by previous studies. 46 − 48 In addition, the chitosan coating layer of the CS-NIO-EA NPs could further improve the physical stability of the NPs 35 because it provided rigidity to the bilayer membrane and reduced the fluidity of the bilayer by removing the phase transition temperature peak of the vesicles. 49 …”