Cytotoxic Effect of Paclitaxel and Lapatinib Co-Delivered in Polylactide-co-Poly(ethylene glycol) Micelles on HER-2-Negative Breast Cancer Cells

Autor: Janusz Kasperczyk, Adam Wilczok, Katarzyna Jelonek, Aleksander Foryś, Suming Li, Monika Musiał-Kulik, Alicja Zajdel
Přispěvatelé: Centre of Polymer and Carbon Materials Polish Academy of Sciences, Institut Européen des membranes (IEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Pharmaceutics
Pharmaceutics, MDPI, 2019, 11 (4), pp.169. ⟨10.3390/pharmaceutics11040169⟩
Pharmaceutics, Vol 11, Iss 4, p 169 (2019)
Volume 11
Issue 4
ISSN: 1999-4923
DOI: 10.3390/pharmaceutics11040169⟩
Popis: International audience; To find better strategies to enhance the cytotoxic effect of paclitaxel (PTX) and lapatinib (LAP) against breast cancer cells, we analyzed the efficacy of a novel delivery system containing polylactide-co-poly(ethylene glycol) (PLA-PEG) filomicelles of over 100 nm in length and spherical micelles of approximately 20 nm in diameter. The 1 H NMR measurements confirmed the incorporation of PTX and LAP into micelles. Analysis of the drug release mechanism revealed the diffusion-controlled release of LAP and anomalous transport of PTX. Drug content analysis in lyophilized micelles and micellar solution showed their good storage stability for at least 6 weeks. Blank micelles, LAP-loaded micelles and free LAP did not affect MCF-7 breast cancer cell proliferation, suggesting that the cytotoxicity of PTX-, PTX/LAP-loaded micelles, and the binary mixture of free PTX and LAP was solely caused by PTX. PTX/LAP-loaded micelles showed greater toxicity compared to the binary mixture of PTX and LAP after 48 h and 72 h. Only free PTX alone induced P-gp activity. This study showed the feasibility of using a LAP and PTX combination to overcome MDR in MCF-7 cells, particularly when co-loaded into micelles. We suggest that PTX/LAP micelles can be applicable not only for the therapy of HER-2-positive, but also HER-2-negative breast cancers.
Databáze: OpenAIRE