ABSTRACT
Topical 5-fluorouracil (5-FU) is approved for the treatment of superficial basal cell carcinoma and actinic keratosis. However, 5-FU suffers from poor skin permeation. Microneedles have been successfully applied to improve the skin permeability of small and large molecules, and even nanoparticles, by creating micron-sized pores in the stratum corneum layer of the skin. In this report, the feasibility of using microneedles to increase the skin permeability of 5-FU was tested. Using full thickness mouse skin mounted on Franz diffusion apparatus, it was shown that the flux of 5-FU through the skin was increased by up to 4.5-fold when the skin was pretreated with microneedles (500 µm in length, 50 µm in base diameter). In a mouse model with B16-F10 mouse melanoma cells implanted in the subcutaneous space, the antitumor activity of a commercially available 5-FU topical cream (5%) was significantly enhanced when the cream was applied on a skin area that was pretreated with microneedles, as compared to when the cream was simply applied on a skin area, underneath which the tumor cells were implanted, and without pretreatment of the skin with microneedles. Fluorouracil is not approved for melanoma therapy, but the clinical efficacy of topical 5-FU against tumors such as basal cell carcinoma may be improved by integrating microneedle technology into the therapy.
ABSTRACT
The steroidal drug prednisolone was encapsulated into microspheres using the biodegradable polymer poly [DL-lactide] using emulsion-solvent evaporation method. The produced microspheres were characterized using scanning electron microscopy, X-ray diffractometery, FT-IR spectroscopy, DSC, and laser light diffraction. The morphology, particle size distribution, encapsulation efficiency [EE%], and drug release showed marked dependence upon formulation parameters viz. initial polymer concentration, surfactant concentration, drug-to-polymer ratio, and volume of the external aqueous phase. The effect of the addition of hydrophilic additives such as PVP or PEG 8000 was also investigated. The encapsulation efficiency percent and the mean particle size were increased by increasing the initial polymer concentration and drug polymer ratio. On the other hand, increasing the surfactant concentration resulted in decreasing the mean particle size and increasing the drug release from the microspheres. The probable mechanism of drug release was estimated and found to be via diffusion through channels and/or pores present within the polymeric matrix. Release data of almost all formulae fitted Higuchi's planar model better than spherical model. This finding could be due to the small extent of drug release [- 40%], or the presence of a large fraction of the encapsulated drug nearby the surface of the microspheres