Targeted drug delivery using smart nanoparticles

Mohammad Javad Sohrabi; Parisa Miralinaghi; Mohammad Reza Sohrabi Renani; Fatemeh  Gharishvandi

doi:10.18502/aptj.v5i3.20514

Mohammad Javad Sohrabi Department of pharmacology, Faculty of pharmaceutical, Damghan Islamic Azad University, Damghan, Iran.
Parisa Miralinaghi Department of Medicinal chemistry, Faculty of pharmaceutical, Damghan Islamic Azad University, Damghan, Iran.
Mohammad Reza Sohrabi Renani Department of medicine, Faculty of medicine, Guilan University of Medical Sciences, Rasht, Iran.
Fatemeh Gharishvandi Department of Clinical Biochemistry, School of Medicine,Tehran University of Medical Sciences, Tehran, Iran.

DOI: https://doi.org/10.18502/aptj.v5i3.20514

Keywords: Targeted Drug Delivery, PLGA-PEG Nanoparticles, Folate Receptor, Dual Stimuli Responsive, Doxorubicin

Abstract

Background: Conventional chemotherapy for cancer treatment is often limited by poor specificity, systemic toxicity, and the development of drug resistance. Targeted drug delivery systems utilizing smart nanoparticles present a promising strategy to overcome these challenges by enhancing therapeutic efficacy and minimizing off-target effects.

Materials and Methods: Folate-conjugated, pH- and temperature-responsive PLGA-PEG nanoparticles encapsulating doxorubicin were synthesized via a nanoprecipitation method. The nanoparticles were characterized for their size, zeta potential, encapsulation efficiency, and drug release kinetics. Their targeting capability and cytotoxicity were evaluated in folate receptor-positive (MCF-7) and negative (NIH-3T3) cell lines using confocal microscopy, flow cytometry, and MTT assays. Furthermore, in vivo pharmacokinetics, biodistribution, antitumor efficacy, and safety were assessed in murine xenograft models.

Results: The formulated nanoparticles were monodisperse (~140 nm) with high drug loading capacity and stability. Folate functionalization significantly enhanced cellular uptake in MCF-7 cells through receptor-mediated endocytosis. Drug release was minimal at physiological pH (7.4) but accelerated significantly under acidic conditions (pH 5.5) and at an elevated temperature (42°C). In vivo studies demonstrated a prolonged circulation time, higher tumor accumulation, and superior tumor growth inhibition (75% reduction) with the targeted nanoparticles compared to both free doxorubicin and non-targeted controls, alongside reduced systemic toxicity.

Conclusion: The integration of active targeting with dual-stimuli responsiveness in this nanoplatform markedly enhances the precision and efficacy of doxorubicin delivery, underscoring its potential for clinical translation in precision oncology.