title: Modulation of polyplex release from biodegradable microparticles through poly(ethylenimine) modification and varying loading concentration.
abstract: OBJECTIVE
  This work investigates the effects of hyaluronic acid (HA) conjugated onto branched poly(ethylenimine) (bPEI) and varying loading concentrations of these polymers complexed with DNA on their release from poly(DL-lactic-co-glycolic acid) (PLGA) microparticles and the transfection of target cells.
  
  
  METHODS
  To examine the effect of alteration of the gene delivery polymer on the system, we observed the morphology, size, loading efficiency, polymer and DNA release, and the transfection efficiency for the microparticles formed with three internal phase loading concentrations during microparticle formation.
  
  
  RESULTS
  Addition of HA to this vector allowed for increased loading concentration within these systems and significantly altered release kinetics without changing the morphology of the particles. The incorporation of HA onto the bPEI backbone significantly increased the transfection efficiency of the complexes released from the corresponding microparticle formulation.
  
  
  CONCLUSIONS
  The results show that the modification of bPEI with HA and the concentration of loaded polymer/DNA complexes can significantly alter the entrapment and release profiles from PLGA microparticles. This is significant in that it offers insight into the effects of modification of gene delivery vectors on a controlled release system designed to achieve a sustained therapeutic response.
authors.affiliation: Department of Bioengineering, Rice University, 6500 Main St, Houston, Texas, 77030, USA.
authors.forename: Clark J
authors.initials: CJ
authors.lastname: Needham
authors.forename: Sarita R
authors.initials: SR
authors.lastname: Shah
authors.forename: Paschalia M
authors.initials: PM
authors.lastname: Mountziaris
authors.forename: F Kurtis
authors.initials: FK
authors.lastname: Kasper
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D000818:Animals; D001388:Aziridines / Q000737:chemistry* / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004247:DNA / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism; D018014:Gene Transfer Techniques; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D014162:Transfection
chemical_list: D001388:Aziridines; D001672:Biocompatible Materials; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033132:aziridine; D006820:Hyaluronic Acid; D004247:DNA