PLGA based particles as "drug reservoir" for antitumor drug delivery: characterization and cytotoxicity studies

Laura Chronopoulou; Fabio Domenici; Sabrina Giantulli; Francesco Brasili; Chiara D'Errico; Georgia Tsaouli; Elisabetta Tortorella; Federico Bordi; Stefania Morrone; Cleofe Palocci; Ida Silvestri

doi:10.1016/j.colsurfb.2019.05.006

PLGA based particles as "drug reservoir" for antitumor drug delivery: characterization and cytotoxicity studies

Colloids Surf B Biointerfaces. 2019 Aug 1:180:495-502. doi: 10.1016/j.colsurfb.2019.05.006. Epub 2019 May 7.

Affiliations

¹ Department of Chemistry , Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
² Department of Physics, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Department of Chemical Science and Technology, University of Rome Tor Vergata, Viale della ricerca scientifica 1, 00133, Rome, Italy. Electronic address: Domenici@Scienze.uniroma2.it.
³ Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
⁴ Department of Physics, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Department of Chemical Science and Technology, University of Rome Tor Vergata, Viale della ricerca scientifica 1, 00133, Rome, Italy.
⁵ Department of Chemical Science and Technology, University of Rome Tor Vergata, Viale della ricerca scientifica 1, 00133, Rome, Italy.
⁶ Department of Physics, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
⁷ Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
⁸ Department of Chemistry , Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy. Electronic address: cleofe.palocci@uniroma1.it.
⁹ Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy. Electronic address: ida.silvestri@uniroma1.it.

PMID: 31103709
DOI: 10.1016/j.colsurfb.2019.05.006

Abstract

Doxorubicin (DOX) is commonly used to treat several tumor types, but its severe side effects, primarily cardiotoxicity, represent a major limitation for its use in clinical settings. In this study we developed and characterized biodegradable and stable poly(D,L-lactic-co-glycolic) acid (PLGA) submicrocarriers employing an osmosis-based patented methodology, which allowed to optimize the drug loading efficiency up to 99%. Proceeding from this, we evaluated on MCF-7, a human breast cancer cell line, the ability of PLGA to promote the internalization of DOX and to improve its cytotoxicity in vitro. We found that the in vitro uptake efficiency is dramatically increased when DOX is loaded within PLGA colloidal carriers, which adhere to the cell membrane behaving as an efficient drug reservoir. In fact, the particles provide a diffusion-driven, sustained release of DOX across the cell membrane, resulting in high drug concentration. Accordingly, the cytotoxic analysis clearly showed that DOX-loaded PLGA exhibit a lower 50% inhibitory concentration than free DOX. The decay time of cell viability was successfully compared with DOX diffusion time constant from PLGA. The overall in vitro results highlight the potential of DOX-loaded PLGA particles to be employed as vectors with improved antitumor efficacy.

Keywords: Anticancer; Burst release; Doxorubicin; Drug delivery; Internalization; PLGA carriers.

MeSH terms

Antineoplastic Agents / pharmacology*
Cell Death / drug effects
Cell Survival / drug effects
Doxorubicin / pharmacology
Drug Carriers / chemistry*
Drug Delivery Systems*
Drug Liberation
Fluorescence
Hemolysis / drug effects
Humans
Kinetics
MCF-7 Cells
Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*

Substances

Antineoplastic Agents
Drug Carriers
Polylactic Acid-Polyglycolic Acid Copolymer
Doxorubicin