Stability,permeation, and cytotoxicity reduction of capsicum extract nanoparticles loaded hydrogel containing wax gourd extract

The aim of this study was to develop hydrogel loaded with capsicum extract nanoparticles and wax gourd extract for transdermal delivery of capsaicin. The addition of wax gourd extract was supposed to reduce cytotoxicity of capsaicin in capsicum extract against HaCaT keratinocyte cell line. Capsicum extract nanoparticles were prepared by solvent displacement method using hyaluronic acid as a stabilizer. The physical and chemical stability of capsicum extract nanoparticles were investigated by dynamic light scattering technique and UV–Visible spectrophotometry, respectively. Hydrogel loaded with capsicum extract nanoparticles and wax gourd fruit extract was then formulated by using Carbopol 940® as a gelling agent for transdermal delivery. The skin permeability of capsaicin from the hydrogel was evaluated by Franz diffusion cell approach. The cytotoxicity reduction of capsicum extract nanoparticles and capsicum extract nanoparticles by mixing with wax gourd extract was determined by MTT assay The results showed that capsicum extract nanoparticles exhibited an average diameter of 168.4 ± 5.3 nm with a polydispersity index and zeta potential value of 0.26 ± 0.01 and −45.7 ± 7.1 mV, respectively. After two month-storage, particle size, polydispersity index, and zeta potential values of capsicum extract nanoparticles stored at 4° C, 30° C, and 45 °C did not significantly change. The capsaicin content decreased to 78%, 71%, and 72% when stored at 4 °C, 30 °C, and 45 °C for three months, respectively. The pH values of hydrogel containing capsicum extract nanoparticles were found to be in the range of 5.58–6.05 indicating good stability. The hydrogel exhibited a pseudoplastic character. The rate of permeation flux of capsaicin from hydrogel was 7.96 µg/cm²/h. A significant increase in cell viability was observed when the cells were incubated with capsicum extract nanoparticles mixed with wax gourd, compared to capsicum extract nanoparticles alone. The wax gourd extract in the hydrogel protected HaCaT cells from capsaicin cytotoxicity, thus may provide a new approach for delivery of capsaicin to reduce cytotoxicity to skin cells.     

Development and characterization of extended release Kollidon SR mini-matrices prepared by hot-melt extrusion

Kollidon^® SR as a drug carrier and two model drugs with two different melting points, ibuprofen and theophylline, were studied by hot-melt extrusion. Powder mixtures containing Kollidon^® SR were extruded using a twin-screw extruder at temperatures 70 and 80 °C for ibuprofen and 80 and 90 °C for theophylline. The glass transition temperature (T_g) and maximum torque were inversely related to ibuprofen concentrations, indicating its plasticizing effect. The results of differential scanning calorimetry (DSC) and X-ray diffraction analysis showed that ibuprofen remained in an amorphous or dissolved state in the extrudates containing drug up to 35%, whereas theophylline was dispersed in the polymer matrix. The increase in amounts of ibuprofen or theophylline in the hot-melt extrudates resulted in the increase in the drug release rates. Theophylline release rate in hot-melt extruded matrices decreased as the extrusion temperature increased. In contrast, a higher processing temperature caused the higher ibuprofen release. This was a clear indication of the plasticizing effect of ibuprofen on Kollidon^® SR and a result from water uptake. Theophylline release rate from hot-melt extrudates decreased with increasing triethyl citrate (TEC) level because of the formation of a denser matrix. By adding of Klucel^® LF as a water-soluble additive to the hot-melt extruded matrices, an increase in ibuprofen and theophylline release rates was obtained.