Tailoring of PEGylated bilosomes for promoting the transdermal delivery of olmesartan medoxomil: in-vitro characterization, ex-vivo permeation and in-vivo assessment

Introduction: The intention of this work was to load olmesartan medoxomil (OLM), a sparsely water soluble antihypertensive bioactive with low oral bioavailability (26%), into PEGylated bilosomes (PBs) for augmenting its transdermal delivery. PBs contain PEGylated single chain edge activator besides the components of traditional bilosomes (Span 60, cholesterol and bile salts). The PEG gives further resilience to vesicle membrane and is speculated to augment both permeability and bioavailability of OLM. Methods: A 2(4) factorial experiment was constructed to inspect the impact of diverse variables on vesicles' features and sort out the optimal formula adopting Design Expert (R) software utilizing thin film hydration technique. Vesicles' evaluation was done by finding out entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and amount of drug released after 6 hrs (Q6h). The optimal formula was selected and characterized for further investigations. Results: The optimal formula (PB15) showed spherical vesicles with EE% of 72.49 +/- 0.38%, PS of 559.30 +/- 10.70 nm, PDI of 0.57 +/- 0.15, ZP of -38.35 +/- 0.65 mV and Q6h of 59.60 +/- 0.24%. PB15 showed higher deformability index (28.39 +/- 5.71 g) compared to traditional bilosomes (5.88 +/- 0.90 g) and transethosomes (14.94 +/- 0.63 g). Further, PB15 showed superior skin permeation from rat's skin relative to the drug suspension. Moreover, confocal laser scanning microscopy examination revealed efficient penetration of the fluoro-labeled PB15 through skin. Histopathological study ensured the safety of PB15. In addition, in-vivo skin deposition studies showed higher OLM deposition in rat's skin from PB15 compared to transethosomes and OLM suspension. Furthermore, pharmacodynamic and pharmacokinetic studies performed using male Wistar rats and male Albino rabbits, respectively, showed the superiority of PB15 over oral tablets. PB15 was found to have significantly higher AUC(0 48) and AUC(0 infinity) relative to the oral tablets. As well, the relative bioavailability of PB15 was found to be 235.04%. Conclusion: Overall, the obtained results confirmed the creditable effect of PB15 for transdermal delivery.