ABSTRACT
The aim of this study was to develop microemulgel for skin delivery of kojic acid. Microemulsions (ME) containing either oleic acid (OA) or caprylic/capric triglycerides as the basic oily components were developed after construction of pseudoternary phase diagrams. Tween 80 was used as surfactant for oleic acid system both in presence and absence of ethanol or propylene glycol (PG) as cosurfactants. For the caprylic/capric systems, Tween 85 was the surfactant in presence or absence of ethanol as cosurfactant. Selected ME formulations were tested for transdermal delivery of kojic acid both in fluid state and after transformation into gel. Incorporation of cosurfactants expanded the microemulsion zone. The cosurfactant free ME were more viscous. Incorporation of kojic acid in ME systems increased the transdermal flux compared to saturated aqueous solution. caprylic/capric ME were more efficient than (OA) based ME. Transformation of the tested ME systems into gel produced significant enhancement in transdermal drug delivery compared with the saturated aqueous drug solution. However, the data revealed superior efficacy for the fluid ME systems over the corresponding microemulgel. In conclusion, both (OA) and caprylic/capric ME were promising for dermal and transdermal delivery of kojic acid even after gel formation.
ABSTRACT
The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil (5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of Poloxamer 407 as a stabilizer. Cubosomes loaded with 5-FU were characterized in vitro and in vivo. In vitro, 5-FU-loaded cubosomes entrapped 31.21% drug and revealed nanometer-sized particles with a narrow particle size distribution. In vitro 5-FU release from cubosomes exhibited a phase of rapid release of about half of the entrapped drug during the first hour, followed by a relatively slower drug release as compared to 5-FU solution. In vivo biodistribution experiments indicated that the cubosomal formulation significantly (P<0.05) increased 5-FU liver concentration, a value approximately 5-fold greater than that observed with a 5-FU solution. However, serum serological results and histopathological findings revealed greater hepatocellular damage in rats treated with cubosomal formulation. These results demonstrate the successful development of cubosomal nanoparticles containing 5-FU for liver targeting. However, further studies are required to evaluate hepatotoxicity and in vivo antitumor activity of lower doses of 5-FU cubosomal formulation in treatment of liver cancer.