Anti-proliferate and apoptosis triggering potential of methotrexate-transferrin conjugate encapsulated PLGA nanoparticles with enhanced cellular uptake by high-affinity folate receptors.

Anti-proliferate and apoptosis triggering potential of methotrexate-transferrin conjugate encapsulated PLGA nanoparticles with enhanced cellular uptake by high-affinity folate receptors.

Artif Cells Nanomed Biotechnol. 2018 May 10;:1-16

Authors: Parmar A, Jain A, Uppal S, Mehta SK, Kaur K, Singh B, Sandhir R, Sharma S

Abstract
The objective of the present study is to enhance the permeation of bioactive molecules across highly lipophilic insurmountable blood brain barrier (BBB) using folic acid (FA) functionalized poly(lactic-co-glycolic acid) (PLGA) nanoparticles (FA-PNPs) coated with non-ionic surfactant, Polysorbate 80 (P80). The developed Mtx-Tf loaded folic acid anchored PNPs formulation depicted particle size, zeta potential and entrapment efficiency of 109 ± 2.3 nm, -9.38 ± 0.9 mV and 71.0 ± 0.6%, respectively. In vitro release showed biphasic release pattern with initial >35% release in 8 h followed by sustained release, up to 65% by the end of 168 h. SRB cyto-toxicity assay depicted P80-Mtx-Tf-FA-PNPs possessing better cellular cyto-toxicity (C6 Glioma) as compared to counter test formulations, i.e. 100 μM nano-encapsulated drug-conjugate concentration incubated for 72 h resulted in apoptosis of ∼100% of the cellular population. Qualitatively, ∼85% of P80-FITC-FA-PNPs have been found to be internalized by C6 glioma cells post 5 h of incubation. Quantitative cellular uptake assay demonstrated a collinear dependence on drug-conjugate concentration. In vivo administration of P80-Mtx-Tf-FA-PNPs depicted significant decrease, i.e. 73.6% in the tumour spheroid volume. Serum analysis data pointed towards the significant relevance of P80-coated FA-PNPs in lowering the drug diffusion rate by 88.4% (after 30 min) and three-fold enhanced retention time of drug in systemic circulation, thereby felicitating an effective prognostic treatment. This study clearly demonstrated reduced systemic toxicity, enhanced biocompatibility and anti-tumour efficacy of formulated NPs.

PMID: 29745729 [PubMed - as supplied by publisher]

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