PMID- 23686375 OWN - NLM STAT- MEDLINE DCOM- 20140127 LR - 20211021 IS - 1573-904X (Electronic) IS - 0724-8741 (Linking) VI - 30 IP - 8 DP - 2013 Aug TI - Co-delivery of vascular endothelial growth factor and angiopoietin-1 using injectable microsphere/hydrogel hybrid systems for therapeutic angiogenesis. PG - 2157-65 LID - 10.1007/s11095-013-1076-6 [doi] AB - PURPOSE: We hypothesized that combined delivery of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) using microsphere/hydrogel hybrid systems could enhance mature vessel formation compared with administration of each factor alone. METHODS: Hybrid delivery systems composed of alginate hydrogels and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres containing angiogenic factors were prepared. The release behavior of angiogenic factors from hybrid systems was monitored in vitro. The hybrid systems were injected into an ischemic rodent model, and blood vessel formation at the ischemic site was evaluated. RESULTS: The sustained release over 4 weeks of both VEGF and Ang-1 from hybrid systems was achieved in vitro. Co-delivery of VEGF and Ang-1 was advantageous to retain muscle tissues and significantly induced vessel enlargement at the ischemic site, compared to mice treated with either VEGF or Ang-1 alone. CONCLUSIONS: Sustained and combined delivery of VEGF and Ang-1 significantly enhances vessel enlargement at the ischemic site, compared with sustained delivery of either factor alone. Microsphere/hydrogel hybrid systems may be a promising vehicle for delivery of multiple drugs for many therapeutic applications. FAU - Shin, Seung-Hwa AU - Shin SH AD - Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea. FAU - Lee, Jangwook AU - Lee J FAU - Ahn, Dong-Gyun AU - Ahn DG FAU - Lee, Kuen Yong AU - Lee KY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130518 PL - United States TA - Pharm Res JT - Pharmaceutical research JID - 8406521 RN - 0 (Alginates) RN - 0 (Angiopoietin-1) RN - 0 (Delayed-Action Preparations) RN - 0 (Hexuronic Acids) RN - 0 (Vascular Endothelial Growth Factor A) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 25852-47-5 (Hydrogel, Polyethylene Glycol Dimethacrylate) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) RN - 8A5D83Q4RW (Glucuronic Acid) SB - IM MH - Alginates/chemistry MH - Angiopoietin-1/*administration & dosage MH - Animals MH - Cell Proliferation/drug effects MH - Delayed-Action Preparations/*chemistry MH - Female MH - Glucuronic Acid/chemistry MH - Hexuronic Acids/chemistry MH - Hindlimb/blood supply/drug effects MH - Hydrogel, Polyethylene Glycol Dimethacrylate/*chemistry MH - Lactic Acid/chemistry MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Microspheres MH - Neovascularization, Physiologic/drug effects MH - Polyglycolic Acid/chemistry MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - Vascular Endothelial Growth Factor A/*administration & dosage EDAT- 2013/05/21 06:00 MHDA- 2014/01/28 06:00 CRDT- 2013/05/21 06:00 PHST- 2013/01/03 00:00 [received] PHST- 2013/05/08 00:00 [accepted] PHST- 2013/05/21 06:00 [entrez] PHST- 2013/05/21 06:00 [pubmed] PHST- 2014/01/28 06:00 [medline] AID - 10.1007/s11095-013-1076-6 [doi] PST - ppublish SO - Pharm Res. 2013 Aug;30(8):2157-65. doi: 10.1007/s11095-013-1076-6. Epub 2013 May 18.