The auto-gelling and drug release properties of the thermosensitive chitosan-β-glycerophosphate for- mulation were investigated. According to rheological study, gelation lag time of chitosan/β-glycerophosphate (GP) solutions varied from 2 to 60min with different deacetylation degree of chitosan, pH, gelation temperature, and the particles in the sol. The gelation properties were also found to influence the release profiles of a hydrophilic drug, 5-fluorouracil (5-FU). Morphological examination by scanning electron microphotography demonstrated that large “pores” occurred during the gel-forming process, which created hydrophilic environment and led to the rapid initial release of the drug (85% in first 8h). Poly-3-hydroxybutyrate (PHB), a biodegradable material, was applied here as scaffold to capture 5-FU into microparticles with high encapsulation efficiency by solvent-nonsolvent method. Combination of these microparticles into the chitosan-β-GP formulation could drop the rapid initial release from 85% down to 29% in the optimized PHB content (75%, by mass). The release could sustain for about 10 months. This study provided an understanding of the potential of injectable implant using thermosensitive chitosan-β-GP formulation containing PHB based particles for the water soluble drugs that need the property of long-term delivery.
Electroporation creates aqueous pathways by short high-voltage pulses resulting in a transient perme- abilization of stratum corneum and an increase in the transdermal delivery rate.However the aqueous pathways will reseal after pulsing,which leads to the rapid drop of transdermal flux.In the present study,the surfactants were added to the donor solution to hinder the shrinkage and resealing of the electropore,and to prolong the lifetime of the aqueous pathways with the consideration that the surfactants could reduce the surface energy of the electropore. These effects of surfactants were demonstrated by the dynamic electrical resistance of the skin and the fluorescent imaging of the local transport regions.Piroxicam(PIX)was transported percutaneously in the presence of surfac- tants in vitro.Owing to the longer lifetime of aqueous pathways,together with the promotion of PIX availability at the barrier exterior and the improvement in the partition of PIX into the aqueous pathways,the presence of surfac- tants led to a remarkable increase in the transdermal delivery rate during electroporation and a significant growth of the accumulative transdermal amount of PIX.
