RESUMO
Objective: To investigate the effect of citronellol (citronellol, CT) on the proliferation of HEp-2 and MCF-7 cells, and prepare CT self-emulsifying drug delivery system (CT-SMs). Its antitumor activity and cell uptake ability of HEp-2 cells in vitro was evaluated. Methods: The effect of CT on the cell proliferation of HEp-2 and MCF-7 were investigated by MTT assay. The pseudo- ternary phase diagram method was used to optimize the formulation of CT-SMs, and the appearance morphology, mean particle size, and Zeta potential were characterized. The effect of CT-SMs on the proliferation of HEp-2 cells was detected by MTT assay and cellular uptake was determined by fluorescence inversion microscopy and flow cytometry. Results: After a certain concentration of CT treatment, MCF-7 cells proliferation was not affected, and the difference was not statistically significant (P > 0.05 compared with the control group), while the proliferative capacity of HEp-2 cells was significantly inhibited (P < 0.05 compared with the control group) in a dose-time dependent manner. The best prescription for CT-SMs was as following: Km (emulsifier:co-emulsifier) was Kolliphor® HS 15:absolute ethanol = 7:3, CT:Km = 3:7, the mean particle size was (354.0 ± 9.5) nm, the appearance was round and spherical with uniform distribution, and the Zeta potential was (-13.4 ± 0.3) mV. The results of cellular uptake experiments showed that the intake of CT-SMs (545.70 ± 11.56) was higher than that of CT (230.00 ± 17.76) in HEp-2 cells treating the same concentration of CT-SMs and CT. Conclusion: CT-SMs could significantly inhibit the proliferation of HEp-2 cells. In this study, CT-SMs were successfully prepared by dropping water method and the quality of CT-SMs was stable and controllable.
RESUMO
The purpose of present study was aimed at developing self emulsifying drug delivery system in liquid and then in pellet form that would result in improved solubility, dissolution and permeability of the poorly water soluble drug carvedilol. Pellets were prepared using extrusion-spheronization technique incorporating liquid SEDDS (carvedilol, capmul MCM EP, cremophore EL, tween 20, propylene glycol), adsorbents ( and crospovidone), microcrystalline cellulose and binder (povidone K-30). Ternary phase diagram was constructed to identify different oil-surfactant-cosurfactant mixtures according to the proportion of each point in it. The optimal CAR-SEDDS pellets showed a quicker redispersion with a droplet size of the reconstituted microemulsion being 160.47 nm, which was almost unchanged after solidification. SEM analysis confirmed good spherical appearance of solid pellets; DSC and XRD analysis confirmed that there was no crystalline carvedilol in the pellets. Pellets were then capable of transferring lipophilic compounds into the aqueous phase and significantly enhancing its release with respect to pure drug.
O propósito do presente estudo foi desenvolver um sistema líquido de liberação de fármacos auto emulsificante e, então, na forma de pélete, que poderia resultar em aprimoramento da solubilidade, da dissolução e permeabilidade do fármaco carvedilol, pouco solúvel em água. Os péletes foram preparados utilizando-se a técnica de extrusão-esferonização, incorporando líquido SEDDS (carvedilol, capmul MCM EP, Cremofor EL, Tween 20, propileno glicol), adsorventes (e crospovidona), celulose microcristallina e ligante (povidona K-30). O diagrama de fase ternário foi construído para identificar as misturas diferentes de óleo-tensoativo-co-tensoativo, de acordo com a proporção em cada ponto delas. Os péletes CAR-SEDDS mostraram redispersão mais rápida, com tamanho de gota da microemulsão reconstituída de 160,47 nm, que se mostrou quase inalterada após a solidificação. A análise por SEM confirmou a aparência esférica dos péletes sólidos. Análise por DSC e XRD confirmou que não havia carvedilol cristalino nos péletes. Estes foram, então capazes de transferir os compostos lipofílicos para a fase aquosa, aumentando, significativamente, sua liberação em relação ao fármaco puro.