Cholesterol-Conjugate as a New Strategy to Improve the Cytotoxic Effect of 5-Fluorouracil on Liver Cancer: Impact of Liposomal Composition.

PURPOSE: Hepatocellular carcinoma (HCC) is a common liver malignancy, which has a low survival rate of all cancers. 5-fluorouracil (5-FU) is clinically recognized to treat HCC. However, the success of this therapy is highly limited due to rapid clearance and non- selective distribution. Cholesterol- conjugate (5-FUC) loaded liposomes proposed to facilitate the transport of 5-FUC into tumor cells via Low-Density Lipoprotein receptor (LDL receptor) that overexpressed in HCC. Thus, the aim of this study was to use 5-FUC loaded liposome as a promising strategy to combat HCC and improve the response of HCC to chemotherapy. METHODS: 5-FUC and 5-FU loaded liposomes were optimized based on Cholesterol (CHO) ratio and type of phospholipid to achieve a potential effect on HCC. Liposomes were prepared by the thin-film hydration method, and evaluated in terms of particle size, polydispersity, zeta potential, Entrapment Efficiency (EE), morphology, drug release and cytotoxicity. RESULTS: The obtained liposomes had a suitable nano-range particle size with negative zeta potential, and acceptable EE%. In vitro drug release of 5-FUC loaded liposomes showed a lower cumulative release over 24 h as compared to 5-FU loaded liposomes. 5-FUC loaded liposomes exhibited a higher in vitro cytotoxic effect as compared to the free drug and 5-FU loaded liposomes against HepG2 cell lines after 48 h via MTT assay. CONCLUSION: These results concluded that 5-FUC loaded liposomes could be used as an alternative tactic to increase the therapeutic index of 5-FU and pave the way for potential clinical applications.

Novel docetaxel chitosan-coated PLGA/PCL nanoparticles with magnified cytotoxicity and bioavailability.

In the present study, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanoparticles were successfully prepared and coated with chitosan (CS). The prepared nanoparticles (NPs) were evaluated for their particle size, zeta potential, particle morphology, drug entrapment efficiency (EE%), and in vitro drug release profile. The anticancer activity of DTX-loaded NPs was assessed in human HT29 colon cancer cell line utilizing MTT assay. The pharmacokinetics of DTX-loaded NPs was monitored in Wistar rats in comparison to DTX solution. The prepared NPs exhibited particle sizes in the range 177.1 ± 8.2-287.6 ± 14.3 nm. CS decorated NPs exhibited a significant increase in particle size and a switch of zeta potential from negative to positive. In addition, high EE% values were obtained for CS coated PCL NPs and PLGA NPs as 67.1 and 76.2%, respectively. Moreover, lowering the rate of DTX in vitro release was achieved within 48 h by using CS coated NPs. Furthermore, a tremendous increase in DTX cytotoxicity was observed by CS-decorated PLGA NPs compared to all other NPs including DTX-free-NPs and pure DTX. The in vivo study revealed significant enhancement in DTX bioavailability from CS-decorated PLGA NPs with more than 4-fold increase in AUC compared to DTX solution. In conclusion, CS-decorated PLGA NPs are a considerable DTX-delivery carrier with magnificent antitumor efficacy.

Di-Block PLCL and Tri-Block PLCLG Matrix Polymeric Nanoparticles Enhanced the Anticancer Activity of Loaded 5-Fluorouracil.

In the current study, 5-FU-loaded nanoparticles (NPs) were prepared using polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), di-block poly lactide-co-caprolactone (PLCL) and tri-block poly L-lactide-co-caprolactone-co-glycolide (PLCLG). The influence of these polymers on the particle sizes, morphology, drug loading, and in vitro drug release was investigated. The anticancer activity was assessed utilizing MTT assay in three human cancer cell lines of different tissue origin; brain (Daoy), liver (HepG2), and colorectal (HT29) using suitable negative and positive controls. The prepared NPs showed a uniform spherical shape with an average size range of 193.5± 6.3 to 303.5± 3.3 nm with negative zeta potential. The entrapment efficiency achieved with F4-F6 (block copolymer NPs) was 78-79% and significantly higher compared with F1 PLGA (31%) and F2; PCL (37%). An initial rapid 5-FU release followed by a slow release ranging from 35% to 81% after 72 h was observed. All the prepared NPs formulations showed enhancement in the cytotoxicity of 5-FU towards all the three cancer cell lines. Generally, block copolymer NPs (F4-F6) showed higher % cell death over PLGA (F1) and PCL (F2) NPs after 48 and 72 h incubation in the case of HepG2 and HT-29. The incorporation of PEG with the tri-block (F6) caused a significant increase in the cytotoxicity of NPs in all of the three cancer cell lines. Block copolymer-based NPs can be considered as promising carriers for enhancing the efficacy of 5-FU in cancer therapy.