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

Abstract

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 ® 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–∞ 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.

Ultra-deformable liposomes containing terpenes (terpesomes) loaded fenticonazole nitrate for treatment of vaginal candidiasis: Box-Behnken design optimization, comparative ex vivo and in vivo studies

“…Albash et al. ( 2019 ) also published similar findings in their investigation on the preparation of olmesartan medoxomil transethosomes they reported that augmenting the amount of SDC participated in the formation of significantly small vesicles owing to micelles formation. Furthermore, the PS of the prepared TPs decreased significantly ( p = .0191) by increasing the concentration of ethanol (X 3 ) from 5% to 15% our results were in accordance with Dragicevic-Curic et al.…”

“…The negative value of the predicted R 2 value of PDI justifies that the mean is a better presenter of the response (Albash et al. 2019 ).…”

“…TPs were assembled by using limonene and citral at different ratios 1:1, 1:2 and 1:3 (w/w) and SDC (10, 20 and 30 mg) employing thin-film hydration approach ( Table 1 ) (Albash et al. 2019 ). At first, phospholipid (100 mg), SDC, terpenes and FTN (10 mg) were dissolved in 10 mL methanol in a round flask.…”

“…About 5 mg from samples was placed in aluminum pan and subjected to heat in a temperature range of 10–250 °C at a rate of 5 °C/min under nitrogen stream (25 mL/min) (Albash et al. 2019 ).…”

“…The permeation flux (J max ) at 12 h and the enhancement ratio (ER) were assessed by the consecutive equation (Albash et al. 2019 ): …”