Advances in Targeted Glioma Therapy with Transferrin-Conjugated Gemcitabine-Loaded PLGA Nanoparticles
Ladi Alik Kumar 1, Gurudutta Pattnaik 1, Bhabani Sankar Satapathy 2, *, Himansu Bhusan Samal 1, *
Journal of Angiotherapy 8(5) 1-11 https://doi.org/10.25163/angiotherapy.859634
Submitted: 27 March 2024 Revised: 12 May 2024 Published: 14 May 2024
Abstract
Primary brain tumor Glioma has one of the highest fatality rates among brain cancers. Conventional chemotherapy for glioma often suffers from off-target drug loss and suboptimal drug availability in brain tissue. This study aimed to develop a targeted strategy for brain cancer cells using transferrin-conjugated, gemcitabine-loaded poly(lactic-co-glycolic acid) nanoparticles (Tf-GB-PLGA-NPs). GB-PLGA-NPs were prepared via solvent evaporation and nanoprecipitation, followed by conjugation with transferrin. The formulation was characterized for physicochemical properties, in-vitro release, cytotoxicity, apoptosis (U87MG cell line), and in-vivo pharmacokinetics. Tf-GB-PLGA-NPs exhibited a particle size of 143±6.23 nm, a PDI of 0.213, a zeta potential of -25 mV, and an entrapment efficiency of 77.53±1.43%. These nanoparticles showed a spherical morphology and sustained release of gemcitabine (76.54±4.08%) over 24 hours. Tf-GB-PLGA-NPs demonstrated significantly higher cell inhibition against the U87MG cell line compared to GB-PLGA-NPs and pure gemcitabine (P<0.05). Apoptosis in U87MG cells was higher with Tf-GB-PLGA-NPs (61.25%) than with GB-PLGA-NPs (31.61%). Additionally, Tf-GB-PLGA-NPs achieved significantly higher concentrations in the brain than pure gemcitabine and GB-PLGA-NPs, with a 11.16-fold increase in AUC0-t (bioavailability) compared to pure gemcitabine solution and a 2.23-fold increase compared to GB-PLGA-NPs. These findings suggest that Tf-GB-PLGA-NPs could be a potent alternative carrier for delivering gemcitabine to the brain for glioma treatment.
Keywords: Glioma, Transferrin, PLGA nanoparticles, Gemcitabine. U87MG. Apoptosis, Pharmacokinetic
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