Dexamethasone-Loaded Reconstitutable Charged Polymeric (PLGA)n-b-bPEI Micelles for Enhanced Nuclear Delivery of Gene Therapeutics

摘要

This study investigates the potential of dexamethasone (Dex) to enhance the nuclear accumulation and subsequent gene expression of plasmid DNA (pDNA) delivered using a charged polymeric micelle-based gene delivery system. (PLGA)_n-b-bPEI_(25kDa) block copolymers are synthesized and used to prepare Dex-loaded cationic micelles (DexCM). After preparing DexCM/pDNA complexes, bPEI_(1.8kDa) is coated on the complexes using a Layer-by-Layer (LbL) technique to construct DexCM/ pDNA/bPEI_(1.8kDa) complexes (i.e., LbL-DexCM polyplexes) that are 100-180nm in diameter and have a zeta potential of 30-40mV. In MCF7 cells, LbLDexCM polyplexes cause 3-13-fold higher transfection efficiencies compared to LbL-CM polyplexes and show negligible cytotoxicity. LbL-DexCM3 polyplexes induce much higher nuclear delivery of pDNA compared to LbL-CM3 polyplexes. These results suggest that Dex-loaded polyplexes could be used in gene and drug delivery applications to increase nuclear accumulation of therapeutic payloads, further leading to a decrease in the dose of the drug and gene necessary to achieve equivalent therapeutic effects.