Bioinspired Folic Acid-ADH-PLGA Polymeric Nanoparticles Loaded with Mangiferin and Piperine: A Promising Strategy for Targeted Delivery in Multidrug-Resistant Lung Cancer Cells

Ritu Jain1, Ritesh Tiwari1, O.P. Agrawal1 and Ajay Kumar Shukla2,*,

1Department of Pharmaceutical Science, Madhyanchal Professional University, Bhopal-462044, India

2Department of Pharmaceutical Science, Institute of Pharmacy, Dr. Rammanohar Lohia Avadh University, Ayodhya-224001, India

*Corresponding author: E-mail:


The current study aims to develop mangiferin and piperine dual drug-loaded folic acid-ADH-PLGA polymeric nanoparticles with bioinspired folic acid modifications which were effective carriers for site-specific delivery in multidrug-resistant lung cancer cells. Mangiferin and piperine, two pharmacological agents, were encapsulated within intelligent nanoparticles. These nanoparticles were fabricated utilizing folic acid, poly(lactic-co-glycolic acid) (PLGA), adipic dihydrazide (ADH) and pluronic F-68 as constituent materials. The successful fabrication of these intelligent polymeric nanoparticles was confirmed through comprehensive characterization employing various analytical techniques, including differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and atomic force microscopy (AFM). The efficacy of the intelligent polymeric nanoparticles against cancer cells was assessed through the evaluation of several parameters and their effectiveness was established utilizing the MTT assay. Furthermore, a hemolytic toxicity test was performed to ascertain whether the nanoparticles exerted any toxic effects on red blood cells. Mangiferin and piperine loaded FAP-M and FAP-P nanoparticles revealed a remarkable potential for inducing cell death. The findings from in vitro drug release assessments, hemolytic toxicity evaluations, bio-distribution analyses, MTT assays and apoptosis assessments exhibited substantial cell cycle phase arrest akin to the standard control. The comprehensive investigation and findings of the internalization process revealed the enhanced anticancer efficacy of mangiferin and piperine encapsulated in fibroblast activation protein-modified (FAP-M) and FAP-P nanoparticles as well as their biodistribution profile.


Mangiferin, Piperine, Folic acid, poly(lactic-co-glycolic acid), Aadipic dihydrazide, Polymeric nanoparticles.

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