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SYSTEMATIC REVIEW article

Front. Pharmacol.

Sec. Experimental Pharmacology and Drug Discovery

This article is part of the Research TopicAdvances in Novel Pharmacotherapeutics and Drug Discovery: Computational, Experimental, Translational, and Clinical Models, Volume IIView all 12 articles

Effectiveness of drug-loaded polyethylene glycol-poly lactic acid-co-glycolic acid nanoparticles in the treatment of breast cancer on in vitro studies: a systematic review

Provisionally accepted
  • 1Universidad Santo Tomas, Santiago, Chile
  • 2Universidad de La Frontera, Temuco, Chile
  • 3Universidad de Talca, Talca, Chile
  • 4Universidad de Los Lagos, Osorno, Chile
  • 5Universidad de La Serena, La Serena, Chile
  • 6Universidad Catolica del Maule, Talca, Chile
  • 7Universidad Vina del Mar, Viña del Mar, Chile
  • 8Universitat de Valencia, Valencia, Spain

The final, formatted version of the article will be published soon.

Background: Breast cancer remains a major therapeutic challenge, driving the need for nanotechnology-based strategies to improve drug delivery and overcome chemoresistance. Poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles - an FDA-approved biodegradable copolymer (lactic + glycolic acids) that degrades into nontoxic metabolites (lactic acid and glycolic acid) - have emerged as promising carriers due to their biocompatibility, sustained release, and ability to enhance cellular uptake of chemotherapeutic agents. This systematic review examined the efficacy of PEG-PLGA nanoparticles loaded with antineoplastic drugs on in vitro models of breast cancer cell lines. Methods: Following PRISMA guidelines, a comprehensive search of Web of Science, EMBASE, MEDLINE, and Scopus identified experimental studies published between 2014 and August 2025 evaluating PEG-PLGA formulations in breast cancer cell lines. Methodological quality was appraised using the National Institute for Health and Care Excellence (NICE) criteria. Results: Thirteen studies met inclusion criteria. PEG-PLGA nanoparticles were predominantly spherical (30-210 nm) and exhibited controlled release kinetics. Compared with free drugs, nanoformulations significantly reduced cell viability, increased apoptosis, and induced cell cycle arrest. Functionalization with ligands such as folic acid enhanced drug targeting and cytotoxicity, while molecular analyses revealed upregulation of p53, Bax, and caspases and downregulation of Bcl-2 and hTERT genes. Conclusion: PEG-PLGA nanoparticles substantially improve the selectivity, bioavailability, and cytotoxic efficacy of anticancer drugs in breast cancer in vitro. These findings underscore their translational potential as next-generation drug delivery systems, warranting in vivo validation and the development of theranostic and stimulus-responsive designs for personalized oncology.

Keywords: breast cancer, PEG-PLGA nanoparticles, Drug Delivery Systems, Antineoplastic Agents, theragnostic

Received: 21 Sep 2025; Accepted: 12 Nov 2025.

Copyright: © 2025 Sandoval, Cárcamo, Lagos, Muñoz, Zavala, Colil, VILLAGRAN SILVA, Vásquez-Carrasco, Hernandez Martinez, Valdés-Badilla, Torrens, Fincheira and Sepúlveda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Edgar Vásquez-Carrasco, edgar.vasquez@utalca.cl
Paulina Sepúlveda, paulina.sepulveda@ufrontera.cl

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