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, *}

Glioma's high mortality and treatment challenges necessitate innovative strategies like nanoparticle-based drug delivery, enhancing therapy efficiency and prognosis.

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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