Development and characterization of miltefosine-loaded polymeric micelles for cancer treatment.

Miltefosine presents antineoplastic activity but high hemolytic potential. Its use in cancer has been limited to treating cutaneous metastasis of breast cancer. To decrease hemolytic potential, we developed a formulation of miltefosine-loaded polymeric micelles (PM) of the copolymer Pluronic-F127. A central composite design was applied and the analysis of variance showed that the optimum level of hydrodynamic diameter and polydispersity index predicted by the model and experimentally confirmed were 29nm and 0.105, respectively. Thermal analyses confirmed that miltefosine was molecularly dispersed within PM. Pluronic-F127 PM with miltefosine 80µM presented a significant reduction of hemolytic effect (80%, p<0.05) in comparison to free drug. In vitro assays against HeLa carcinoma cells demonstrated similar cytotoxicity to free miltefosine and PM. Our results suggest that, by lowering hemolytic potential, miltefosine-loaded Pluronic-F127 PM a promising alternative to broaden this drug use in cancer therapy, as well as of other alkylphosphocholines.

Preparation, characterization and in vitro evaluation of ε-polylysine-loaded polymer blend microparticles for potential pancreatic cancer therapy.

Peptide active ingredients show great promise regarding the treatment of various health-endangering diseases. It is reported that L-lysine inhibits the proliferation of several tumour lines in vitro and in vivo. However, proteins and peptide drugs possess certain disadvantages such as in vivo instability and short biological half-life. On the grounds that drug delivery systems can overcome a wide spectrum of bioactive compounds issues, a biopolymeric blend-based microparticulated system capable of delivering ε-polylysine (PLL) was developed. PLL-loaded poly((L)Lactic acid)/poly(D,L-Lactide)-co-poly(ethylene glycol)-based microparticles (PLL-PB-MPs) were prepared and fully characterised exhibiting a narrow size distribution (1.2 ± 0.12 µm), high loading efficiency (81%) and improved thermal stability (Td from 250 °C to 291 °C). The cytotoxicity and antiproliferative effect of PLL-PB-MPs in pancreatic adenocarcinoma cell lines BxPC3 and MIA PaCa-2 were confirmed. Due to their physicochemical and biopharmaceutical properties, PB-MPs constitute a promising carrier to deliver bioactive peptides.