DEVELOPMENT AND CHARACTERIZATION OF PROTRANSFERSOMES LOADED WITH MODEL DRUG FOR TRANSDERMAL DELIVERY

Abstract

Repaglinide (REP) is an oral synthetic antidiabetic that is administered to enhance meal-induced insulin production. It is quickly excreted from the body through the biliary system. Due its first-pass metabolism that occurs in the liver, REP has a low oral bioavailability of 56%. Its half-life in systemic blood circulation is approximately one hour, and it has a high plasma protein binding (greater than 98%). In addition to having a high lipophilicity (log P = 3.97) and extremely low water solubility (34 μg/mL at 37°C), REP also has a low and inconsistent bioavailability. The objective of this study was to develop a nanocarrier system called protransfersomes loaded with repaglinide REP-PTFs that provides the benefits of prolonged drug release and enhanced its bioavailability. Fabrication of REP loaded protransfersome nanovesicle by using different types of surfactants (tween 80, span 60, poloxamer188, and their combinations). All six different REP-PTF NVs formulations with different edge activator were prepared and characterized by measurements of Particle size (PS), polydispersity index (PDI); Zeta potential analysis (ZP) and % Entrapment efficiency (EE) were used as input parameters in Rank order to find the most optimal REP-PTF NVs composition. The results demonstrated that altering the type of surfactant had a significant impact on the Particle size (PS), polydispersity index (PDI); Zeta potential analysis (ZP) and % Entrapment efficiency (EE) of the REP-PTFs. The average particle size varied between 184.7 ± 9.7 and 629.7 ± 172.5 nm. The particles exhibited a negative charge, with zeta potential values ranging from −37.77 ± 1.77 to −29.1 ± 1.03 mV. The % E.E varied between 78±4.9 and 95.8±3.2 %. REP-PTFs exhibited prolonged drug release compared to the dissolution of REP suspension. Topical application of protransfersomes onto the abdominal skin of hairless mice resulted in better drug absorption than REP free. In conclusion, these results suggested that protransfersome has the potential to deliver REP via transdermal routes.