<p>Use of transethosomes for enhancing the transdermal delivery of olmesartan medoxomil: in vitro, ex vivo, and in vivo evaluation</p>

Abstract

Introduction and aim: Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability due to extensive first-pass metabolism. This study aimed to prepare transetho somes (TEs) for enhancing the transdermal delivery of OLM to avoid its oral problems. Methods: TE formulae were prepared utilizing 5 1 .3 1 full factorial design using various surfactants (SAAs) and different phospholipid-to-SAA ratios. The formulae were characterized regarding their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and the amount of drug released after 6 hours (Q6h). Design Expert ® software was employed to select the optimum formula. Results: The optimum formula (TE14) had an EE% of 58.50%±1.30%, PS of 222.60±2.50 nm, PDI of 0.11±0.06, ZP of-20.80±0.30 mV, and Q6h of 67.40%±0.20%. In addition, TE14 was compared to transferosomes (TFs) in terms of elasticity and was found to show higher deformability index. Further, evaluation of ex vivo permeation using both rat and shed snake skin showed higher permeability of TE14 compared to TFs and OLM suspension. Confocal laser scanning microscopy confirmed the capability of the fluoro-labeled TE14 to penetrate deep within the skin, while the histopathological study confirmed its safety. TE14 successfully maintained normal blood pressure values of rats up to 24 hours. Moreover, TE14 showed superiority in dermatokinetic study when compared with drug suspension. Conclusion: Taken together, the obtained results confirmed the potential of employing TEs as a successful carrier for the transdermal delivery of OLM.

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

“…For preparing traditional bilosomes, Span 60 (50 mg), cholesterol (25 mg) and STC (15 mg) were added in 10 mL chloroform: methanol mixture (2:1) (v/v) in 250 mL round bottom flask and the organic phase was then removed and the film was hydrated by 10 mL distilled water and then bilosomes were sonicated for 10 mins. In addition, transethosomes composed of SDC (15 mg) and phospholipid (85 mg) were developed also by thin film hydration technique and the film was hydrated using 10 mL distilled water containing 4% v/v ethanol and the preparation was continued as mentioned in our previous work 11Table 1The levels of independent variables and the model summary statistics of 2 4 full factorial design used for optimization of OLM loaded PBsFactors (independent variables)Levels of variables X 1 : BS type SDCSTC X 2 : EA type Brijo20Brij52 X 3 : BS amount (mg) 515 X 4 : EA amount (mg) 1525 Responses (dependent variables) R 2 Adjusted R 2 Predicted R 2 Constraints p -value F value Adequate precision Significant factors Y 1 : EE% 0.970.960.95Maximize<0.0001101.0033.92x 1 , x 2 , x 3 , x 4 Y 2 : PS (nm) 0.740.620.41Minimize0.00026.209.11x 1 , x 2 , x 3 , x 4 Y 3 : PDI 0.27−0.06−0.67Minimize0.620.813.45- Y 4 : ZP (mV) 0.750.64…”

“…Confocal laser scanning microscopy was applied to track the intensity of penetration of the fluoro-labeled optimal PB through skin layers. To assess vesicles’ membrane elasticity and the role played by Brij ® , the deformability index of optimal PB was compared with transethosomes prepared in our previous work11 and traditional bilosomes. Moreover, the safety of the prepared PBs was assured using histopathology.…”

Phospholipid Vesicles for Dermal/Transdermal and Nasal Administration of Active Molecules: The Effect of Surfactants and Alcohols on the Fluidity of Their Lipid Bilayers and Penetration Enhancement Properties

“…Song e al., [55] added the surfactants to the final ethosomal system, while Rady et al [56] dissolved them with the lipid content in ethanol. Other investigations used the thin layer evaporation method to obtain these vesicular carriers [63,64].…”

“…In a recent study by Albash et al, [64] the anti-hypertensive effect of an olmesartan medoxomil transethosomal system was evaluated in rats with elevated blood pressure. The effect of the transethosomes applied onto the skin was compared to that of oral administration of a commercial tablet.…”

Deriye İlaç Uygulanması için Transetozomların Formülasyonu ve İn vitro Karakterizasyonu

“…Transetozomların etken maddenin her iki model membrandan geçişini transferzomlara göre arttırmıştır. 1 Bir başka çalışmada progesteron yüklü transetozomlar enjeksiyon-sonikasyon yöntemi le hazırlanarak jelleştirilmiş ve bu transetozomal jelin vajina mukozasından permeas-yonu çalışılmıştır. Serbest etken madde içeren kontrol jel formülasyonu ile karşılaştırıldığında transetozomal jelden progesteron permeasyonunun daha fazla ve kontrollü olarak gerçekleştiği bildirilmiştir.…”