International Journal of
Advanced Multidisciplinary Application

Volume 3, Issue 5

• Author(s)Aniket Sharma, Sunita Y., Rohit Joshi
• AffiliationDepartment of Biotechnology, Maharishi Markandeshwar University, Ambala, Haryana, India
• Page No.95-101
• Volume, Issue & YearVolume 3, Issue 5, May 2026
• Published On2026/05/15
• JournalInternational Journal of Advanced Multidisciplinary Application (IJAMA)
• ISSN No.3048-9350
• DOIhttps://doi.org/10.5281/zenodo.20423067

Abstract

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.

Keywords: nanoparticles, PLGA-PEG, chitosan, doxorubicin, breast cancer, targeted drug delivery, EPR effect, pharmacokinetics, MTT assay, Box-Behnken design

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