Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 109, Issue 3, Pages 1297-1302Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2019.11.011
Keywords
liposomes; nanoparticles; formulation; drug delivery systems; controlled release
Funding
- Italian Ministry for University and Research (MIUR)-Universita degli Studi di Torino, Fondi Ricerca Locale
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Initially developed as a synthetic analogue of insulin, pentamidine (PTM) is an antimicrobial drug that has recently shown in vitro and in vivo anticancer activity. Nevertheless, systemic administration of PTM causes severe side effects, especially nephrotoxicity. Here we propose the association of PTM to different biocompatible nanosystems in order to compare the physicochemical characteristics of the loaded nanocarriers and their influence on the drug cytotoxicity toward cancer cells. In particular, PTM (as free base or with different counterions) was encapsulated into liposomes and poly(lactide-co-glycolide) (PLGA) nanoparticles and all the formulations have been deeply characterized concerning mean diameter, polydispersity index, zeta potential, stability, morphology, PTM loading, and drug release profile. The anticancer activity was evaluated on a human ovarian cancer cell line over 72 h. Results showed that PTM is efficiently loaded into liposomes with a transmembrane citrate or sulfate gradient; concerning PLGA nanoparticles, important association occurred, thanks to ionic interactions between the drug and the polymer. The in vitro studies confirmed the anticancer activity of PTM, which was gradually released with different profiles depending on the drug form and the nanocarrier structure. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
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