Structural Characterization by Scattering and Spectroscopic Methods and Biological Evaluation of Polymeric Micelles of Poloxamines and TPGS as Nanocarriers for Miltefosine Delivery

Publication date: Available online 25 January 2020Source: International Journal of PharmaceuticsAuthor(s): Joan Puig-Rigall, Celia Fernandez-Rubio, Javier González-Benito, Judith E. Houston, Aurel Radulescu, Paul Nguewa, Gustavo González-GaitanoAbstractMiltefosine (MF), an alkylphospholipid originally developed for breast cancer treatment, is a highly active drug for the treatment against leishmaniasis, a neglected tropical disease considered the world’s second leading cause of death by a parasitic agent after malaria. MF exhibits dose-limiting gastrointestinal side effects in patients and its penetration through lipophilic barriers is reduced. In this work we propose a reformulation of MF by incorporating the drug to poly(ethylene)oxide (PEO)-based polymeric micelles, specifically, D-α-tocopheryl polyethylene glycol succinate (TPGS) and Tetronic block copolymers (T904 and T1107). A full structural characterization of the aggregates has been carried out by SANS (small-angle neutron scattering) and dynamic light scattering (DLS), in combination with proton 1D and 2D NMR spectroscopy, to determine the precise location of the drug. The structure of MF micelles has been characterized as a function of the temperature and concentration. In the presence of the polymers, MF forms mixed micelles in a wide range of temperatures, TPGS being the co-surfactant that incorporates more MF unimers. The hydrophobic parts of MF and the block copolymers are in close contact within the micel...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research