ABSTRACT
Tumor-targeted nanoparticle delivery system has been known as a substitute and capable achievement in cancer treatment compared to conventional methods. In this study, we examined potential application of É-tocotrienol-Precirol formulation to enhance efficiency of doxorubicin (DOX) in induction of apoptosis in HUH-7 hepatocarcinoma cells. É-tocotrienol-loaded nanoparticles were characterized at the point of zeta potential, particle size, scanning electron microscope (SEM), and cell internalization. To evaluate antiproliferative effects of formulation, apoptosis, cell cycle procedure, flow cytometry, and MTT assays were employed. Optimum size of the É-tocotrienol formulation revealed narrow size distribution with mean average of 78 ± 3 nm. IC50 values for É-tocotrienol and É-tocotrienol-nano structured lipid carriers after 24 h were 15 ± 0.6 and 10 ± 0.03 µM, respectively. After incubation of cells with É-tocotrienol-loaded careers, the rate of cell proliferation decreased from 53 ± 6.1 to 34 ± 7.1% (P < 0.05). A significant improvement in the apoptosis percentage was revealed after treatment of the HUH-7 cell line with DOX and É-tocotrienol careers (P < 0.05). Gene expression results demonstrated a marked decrease in survivin and increase in Bid and Bax levels. Our findings suggest that É-tocotrienol-loaded nanoparticles elevate DOX efficacy in HUH-7 hepatocarcinoma cell.
Subject(s)
Carcinoma, Hepatocellular/drug therapy , Diglycerides/chemistry , Doxorubicin/pharmacology , Liver Neoplasms/drug therapy , Tocotrienols/chemistry , Apoptosis/drug effects , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Dose-Response Relationship, Drug , Doxorubicin/chemistry , Drug Compounding , Humans , Liver Neoplasms/pathology , Nanoparticles , Survivin/genetics , bcl-2-Associated X Protein/geneticsABSTRACT
OBJECTIVE: Dermal delivery of Doxorubicin (Dox) would be an ideal way in maximising drug efficiency against skin cancer accompanying with minimising side effects. We investigated the potential of Dox-loaded Solid lipid nanoparticles (SLNs) for topical delivery against skin cancer. METHODS: In vitro and in vivo cytotoxicity of optimised formulation were evaluated on murine melanoma (B16F10) cells by MTT assay and melanoma induced Balb/C mice, respectively. Animal study followed by histological analysis. RESULTS: Optimised formulation showed mean particle size and encapsulation efficiency (EE) of 92 nm and 86% w/w (0.86% w/w value of encapsulated Dox in the lipid matrix), respectively. FTIR experiment confirmed drug-lipid interaction interpreting the observed high EE value for Dox. In vitro and in vivo results indicated the superiority of cytotoxic performance of Dox-loaded SLN compared to Dox solution. CONCLUSION: Our findings may open the possibilities for the topical delivery of Dox to the skin cancerous tissues.
