PMID- 23884567 OWN - NLM STAT- MEDLINE DCOM- 20140811 LR - 20211021 IS - 1573-904X (Electronic) IS - 0724-8741 (Linking) VI - 31 IP - 1 DP - 2014 Jan TI - Modulation of polyplex release from biodegradable microparticles through poly(ethylenimine) modification and varying loading concentration. PG - 77-85 LID - 10.1007/s11095-013-1133-1 [doi] AB - PURPOSE: 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. FAU - Needham, Clark J AU - Needham CJ AD - Department of Bioengineering, Rice University, 6500 Main St, Houston, Texas, 77030, USA. FAU - Shah, Sarita R AU - Shah SR FAU - Mountziaris, Paschalia M AU - Mountziaris PM FAU - Kasper, F Kurtis AU - Kasper FK FAU - Mikos, Antonios G AU - Mikos AG LA - eng GR - R01 AR57083/AR/NIAMS NIH HHS/United States GR - R21 AR56076/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130725 PL - United States TA - Pharm Res JT - Pharmaceutical research JID - 8406521 RN - 0 (Aziridines) RN - 0 (Biocompatible Materials) RN - 0 (Polymers) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) RN - 54P5FEX9FH (aziridine) RN - 9004-61-9 (Hyaluronic Acid) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Aziridines/*chemistry/metabolism MH - Biocompatible Materials/*chemistry/metabolism MH - Cells, Cultured MH - Chemistry, Pharmaceutical/methods MH - DNA/chemistry MH - Fibroblasts/metabolism MH - Gene Transfer Techniques MH - Hyaluronic Acid/*chemistry/metabolism MH - Lactic Acid/chemistry/metabolism MH - Microspheres MH - Particle Size MH - Polyglycolic Acid/chemistry/metabolism MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - Polymers/*chemistry/metabolism MH - Rats MH - Transfection EDAT- 2013/07/26 06:00 MHDA- 2014/08/12 06:00 CRDT- 2013/07/26 06:00 PHST- 2013/04/30 00:00 [received] PHST- 2013/06/24 00:00 [accepted] PHST- 2013/07/26 06:00 [entrez] PHST- 2013/07/26 06:00 [pubmed] PHST- 2014/08/12 06:00 [medline] AID - 10.1007/s11095-013-1133-1 [doi] PST - ppublish SO - Pharm Res. 2014 Jan;31(1):77-85. doi: 10.1007/s11095-013-1133-1. Epub 2013 Jul 25.