title: Local drug delivery system: inhibition of inflammatory angiogenesis in a murine sponge model by dexamethasone-loaded polyurethane implants.
abstract: Implants are defined as controlled sustained release delivery systems of therapeutic agents incorporated or dispersed into a polymeric carrier. These systems can be implanted in specific organs and delivered by the therapeutic agents at the target site to treat various pathological processes. In the present study, the effects of dexamethasone-loaded polyurethane implants [PU ACT (dexamethasone acetate) implants] on inflammatory angiogenesis in a murine sponge model were investigated. PU ACT implants were inserted into nonbiocompatible sponges, used as a framework for fibrovascular tissue growth, and implanted into subcutaneous tissue located on the back of mice. After 7 days of implantation, the implant system was collected and processed for the assessment of hemoglobin (Hb; vascular index), myeloperoxidase (MPO), and N-acetyl-β-D-glucosaminidase (NAG; inflammatory enzymes activities) and collagen content. ACT released from the polymeric implants provided a significant decrease in the neovascularization in the sponge (Hb content). PU ACT implants provided no effects on neutrophil infiltration (MPO activity) but macrophage recruitment was affected by the glucocorticoid delivered by implants (NAG activity). ACT released from implants was able to reduce the collagen deposition. The qualitative histological findings corroborated with the measured biochemical parameters. These local drug delivery systems derived from polyurethane efficiently modulated the key components of inflammation, angiogenesis, and fibrosis induced by sponge discs in an experimental animal model.
authors.affiliation: Center of Research in Biological Science, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
authors.forename: Sandra A L
authors.initials: SA
authors.lastname: Moura
authors.forename: Luiza Dias C
authors.initials: LD
authors.lastname: Lima
authors.forename: Sílvia Passos
authors.initials: SP
authors.lastname: Andrade
authors.forename: Armando
authors.initials: A
authors.lastname: Da Silva-Cunha
authors.forename: Rodrigo L
authors.initials: RL
authors.lastname: Órefice
authors.forename: Eliane
authors.initials: E
authors.lastname: Ayres
authors.forename: Gisele Rodrigues
authors.initials: GR
authors.lastname: Da Silva
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D015415:Biomarkers / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003094:Collagen / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D004343:Drug Implants; D005260:Female; D005355:Fibrosis; D006454:Hemoglobins / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism; D011140:Polyurethanes / Q000737:chemistry*; D015503:Surgical Sponges; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D004337:Drug Carriers; D004343:Drug Implants; D006454:Hemoglobins; D011140:Polyurethanes; D003907:Dexamethasone; D003094:Collagen; C018038:dexamethasone acetate; D009195:Peroxidase; D000117:Acetylglucosamine