Design and Pharmacokinetic Evaluation of a Nanoparticle-Enabled Dual Drug Delivery System for Targeted Chemotherapy in Multidrug-Resistant Breast Cancer Models
Keywords:
Multidrug resistance, breast cancer, nanoparticles, dual drug delivery, doxorubicin, verapamil, pharmacokinetics, P-glycoprotein inhibition, targeted therapyAbstract
Purpose: The emergence of multidrug resistance (MDR) in breast cancer remains a formidable obstacle to effective chemotherapy. This study aims to design a dual-drug encapsulated nanoparticle (NP) system to co-deliver doxorubicin (DOX) and verapamil (VRP), a P-glycoprotein (P-gp) inhibitor, to overcome MDR in breast cancer cells through targeted and synergistic action.
Methodology: A biocompatible, PEGylated PLGA-based NP formulation was synthesized via double emulsion solvent evaporation. DOX and VRP were co-encapsulated and conjugated with folic acid for active targeting. Pharmacokinetic profiles were studied in murine xenograft models of MDR breast cancer, with biodistribution and tumor accumulation measured via fluorescence imaging and HPLC quantification.
Findings: The NP system exhibited high drug-loading efficiency and sustained release. In vivo pharmacokinetics showed prolonged circulation time and preferential tumor accumulation. Co-delivery significantly enhanced cytotoxicity and reduced tumor size in MDR models, outperforming free-drug combinations.
Practical implications: This delivery platform offers a promising avenue for circumventing P-gp-mediated drug efflux, addressing one of the major challenges in MDR breast cancer chemotherapy.
Originality: The study provides an integrative therapeutic strategy using dual-functional nanocarriers for MDR reversal, with implications for future clinical translation in resistant cancers.
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