PLGA-PEG nanoparticles for doxorubicin delivery demonstrated a significantly lower IC50 (0.68 µg/mL) compared to free doxorubicin (1.24 µg/mL) and a 3.8-fold greater in vivo AUC.
PLGA-PEG nanoparticles demonstrate superior sustained release, reduced cytotoxicity, and an enhanced pharmacokinetic profile compared to free doxorubicin in preclinical models.
Effect estimate: 3.8-fold greater AUC
Absolute Event Rate: 0.68% vs 1.24%
Breast cancer remains the most prevalent malignancy in women globally, accounting for approximately 2.3 million new diagnoses annually. Conventional chemotherapy with doxorubicin (DOX) is hampered by dose-limiting cardiotoxicity and non-specific systemic distribution, necessitating nanoparticle-based targeted delivery systems capable of prolonging circulation time and enhancing tumour accumulation through the enhanced permeability and retention (EPR) effect. Objective: To formulate, optimise, and comparatively evaluate PLGA-PEG and chitosan nanoparticle systems for sustained DOX delivery with improved therapeutic index. Methods: Nanoparticles were prepared by nanoprecipitation (PLGA-PEG) and ionic gelation (chitosan), optimised using a 3² Box-Behnken design, and characterised for size, PDI, zeta potential, and encapsulation efficiency. In vitro release was studied in PBS (pH 7.4 and pH 5.0). Cytotoxicity, cellular uptake, and apoptosis were evaluated in MCF-7 cells. Pharmacokinetic and biodistribution studies were conducted in Sprague-Dawley rats bearing xenograft tumours. Results: PLGA-PEG NPs showed mean size 142±8 nm, zeta potential −28.4±2.1 mV, encapsulation efficiency 84.2%, and sustained 72-hour release. Chitosan NPs showed size 197±11 nm, zeta potential +22.1±1.8 mV, and pH-responsive release. MTT assay IC50 for PLGA-PEG NPs (0.68 µg/mL) was significantly lower than free DOX (1.24 µg/mL). In vivo AUC for PLGA-PEG NPs was 3.8-fold greater than free drug. Conclusion: PLGA-PEG nanoparticles demonstrate superior sustained release, reduced cytotoxicity to normal cells, and significantly enhanced pharmacokinetic profile, positioning them as a clinically translatable platform for targeted breast cancer chemotherapy.
Aniket Sharma, Sunita Y., Rohit Joshi (Thu,) conducted a other in Breast cancer. PLGA-PEG and chitosan nanoparticles for doxorubicin delivery vs. Free doxorubicin was evaluated on MTT assay IC50 in MCF-7 cells (3.8-fold greater AUC). PLGA-PEG nanoparticles for doxorubicin delivery demonstrated a significantly lower IC50 (0.68 µg/mL) compared to free doxorubicin (1.24 µg/mL) and a 3.8-fold greater in vivo AUC.