title: Dexamethasone-loaded reconstitutable charged polymeric (PLGA)n -b-bPEI micelles for enhanced nuclear delivery of gene therapeutics.
abstract: 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-bPEI25kDa block copolymers are synthesized and used to prepare Dex-loaded cationic micelles (DexCM). After preparing DexCM/pDNA complexes, bPEI1.8kDa is coated on the complexes using a Layer-by-Layer (LbL) technique to construct DexCM/pDNA/bPEI1.8kDa complexes (i.e., LbL-DexCM polyplexes) that are 100-180 nm in diameter and have a zeta potential of 30-40 mV. In MCF7 cells, LbL-DexCM 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.
authors.affiliation: Department of Bioengineering, The University of Utah, 20 S. 2030 E., Rm. 108, Salt Lake City, Utah, 84112, USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Mishra
authors.forename: Han Chang
authors.initials: HC
authors.lastname: Kang
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
mesh_terms: D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000737:chemistry*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008823:Micelles; D011094:Polyethyleneimine / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D008823:Micelles; D011098:Polyglactin 910; D003907:Dexamethasone; D011094:Polyethyleneimine
keywords: co-delivery; dexamethasone; nuclear delivery; polymeric gene delivery; polymeric micelle