Development of thalidomide-loaded biodegradable devices and evaluation of the effect on inhibition of inflammation and angiogenesis after subcutaneous application
| Autor: | Gisele Rodrigues Da Silva, Armando Silva-Cunha, Silvia Passos Andrade, Rogéria Serakides, Sílvia Ligório Fialho, Pedro A F Souza, Leandro Flores Batista, Wagner da Nova Mussel, Bruno Gonçalves Pereira |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.drug_class
Angiogenesis Injections Subcutaneous Biocompatible Materials Inflammation Pharmacology Anti-inflammatory Hemoglobins Mice chemistry.chemical_compound Polylactic Acid-Polyglycolic Acid Copolymer X-Ray Diffraction In vivo Acetylglucosaminidase medicine Animals Lactic Acid Peroxidase Skin Calorimetry Differential Scanning Neovascularization Pathologic business.industry General Medicine Thalidomide Disease Models Animal PLGA chemistry Toxicity Female Implant medicine.symptom business Polyglycolic Acid medicine.drug |
| Zdroj: | Biomedicine & Pharmacotherapy. 71:21-28 |
| ISSN: | 0753-3322 |
| DOI: | 10.1016/j.biopha.2015.02.003 |
| Popis: | Purpose To develop thalidomide-loaded poly-lactide-co-glycolide implants and evaluate its in vivo release and biological activity against inflammation and angiogenesis after subcutaneous administration. Methods Implants were prepared by the hot molding technique and characterized using stereomicroscopy, thermal analysis and X-ray diffraction. Swiss mice, divided in groups 1–3, received a subcutaneous implant containing 25% (w/w), 50% (w/w) or 75% (w/w) of thalidomide, respectively (n = 6). The drug levels were determined during a 28-day study period. The toxicity associated with the implants was evaluated by light microscopy. The potential of the developed implant in the inhibition of inflammation and angiogenesis was evaluated in vivo using the sponge model. Results Thalidomide implant was developed and its characterization proved the stability of the drug and the polymer during preparation. Release profiles in vivo demonstrated an extended release of thalidomide from the implants during the 28 days. Histological evaluation did not show any sign of intense local inflammatory response to the presence of the implants in the subcutaneous pouch. The thalidomide implant reduced the number of vessels and N-acetyl-b-glucosaminidase (NAG) in vivo. Conclusion The biodegradable implants delivered safe doses of thalidomide that were also effective to induce angiogenesis and inflammation regression. |
| Databáze: | OpenAIRE |
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