title: Sequential delivery of TAT-HSP27 and VEGF using microsphere/hydrogel hybrid systems for therapeutic angiogenesis.
abstract: Ischemic disease is associated with high mortality and morbidity rates, and therapeutic angiogenesis via systemic or local delivery of protein drugs is one potential approach to treat the disease. In this study, we hypothesized that combined delivery of TAT-HSP27 (HSP27 fused with transcriptional activator) and VEGF could enhance the therapeutic efficacy in an ischemic mouse model, and that sequential release could be critical in therapeutic angiogenesis. Alginate hydrogels containing TAT-HSP27 as an anti-apoptotic agent were prepared, and porous PLGA microspheres loaded with VEGF as an angiogenic agent were incorporated into the hydrogels to prepare microsphere/hydrogel hybrid delivery systems. Sequential in vitro release of TAT-HSP27 and VEGF was achieved by the hybrid systems. TAT-HSP27 was depleted from alginate gels in 7 days, while VEGF was continually released for 28 days. The release rate of VEGF was attenuated by varying the porous structures of PLGA microspheres. Sequential delivery of TAT-HSP27 and VEGF was critical to protect against muscle degeneration and fibrosis, as well as to promote new blood vessel formation in the ischemic site of a mouse model. This approach to controlling the sequential release behaviors of multiple drugs could be useful in the design of novel drug delivery systems for therapeutic angiogenesis.
authors.affiliation: Department of Bioengineering and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Seung-Hwa
authors.initials: SH
authors.lastname: Shin
authors.forename: Jangwook
authors.initials: J
authors.lastname: Lee
authors.forename: Kwang Suk
authors.initials: KS
authors.lastname: Lim
authors.forename: Taiyoun
authors.initials: T
authors.lastname: Rhim
authors.forename: Sang Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Yong-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Kuen Yong
authors.initials: KY
authors.lastname: Lee
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D005263:Femoral Artery / Q000187:drug effects / Q000473:pathology; D015696:Gene Products, tat / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D055551:HSP27 Heat-Shock Proteins / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D020100:Hydrogels / Q000737:chemistry*; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D012995:Solubility; D013499:Surface Properties; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000464:Alginates; D004337:Drug Carriers; D004338:Drug Combinations; D015696:Gene Products, tat; D055551:HSP27 Heat-Shock Proteins; D020100:Hydrogels; D011993:Recombinant Fusion Proteins; C582517:TAT-HSP27 fusion protein, human; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid