Designing and Formulation Optimization of Hyaluronic Acid Conjugated PLGA Nanoparticles of Tamoxifen for Tumor Targeting.

Abstract

BACKGROUND\nTamoxifen is widely used for treatment of estrogen receptor positive breast cancer. It is, however, associated with severe side effects of cancerous proliferation on uterus endometrium. The tumor targeting formulation strategies can effectively overcome drug side effects of tamoxifen and provide safer drug treatment.\n\n\nOBJECTIVE\nDesigning tumor targeted PLGA nanoparticles of tamoxifen by attaching hyaluronic acid (HA) as ligand to actively target the CD44 receptors present at breast cancer cells surface.\n\n\nMETHODS\nPLGA-PEG-HA conjugate was synthesized in the laboratory and its tamoxifen loaded nanoparticles were fabricated and characterized by FTIR, NMR, DSC, and XRD analysis. Formulation optimization was done by Box- Behnken design using Design Expert software. The formulations were evaluated for in- vitro drug release and cytotoxic effect on MCF-7 cell lines.\n\n\nRESULTS\nThe particle size, PDI, and drug encapsulation efficiency of optimized nanoparticles were 294.8, 0.626, and 65.16% respectively. Optimized formulation showed 9.56 % burst release and sustained drug release for 8 h. The drug release was effected by non-fickian diffusion process supplemented further by erosion of polymeric matrix and followed korsmeyer-Peppas model. MTT cell line assay shows 47.48 % cell mortality when treated with tamoxifen loaded PLGA-PEG-HA nanoparticles.\n\n\nCONCLUSION\nHyaluronic acid conjugated PLGA-PEG nanoparticles of tamoxifen were designed for active targeting to breast cancerous cells. The results of MTT assay showed that tamoxifen nanoparticles formulation was more cytotoxic than tamoxifen drug alone which is attributed to their preferential uptake by cell lines by affinity of CD44 receptors of cell lines to HA ligand present in nanoparticles.