RESUMO
A novel micelle based on heparosan and deoxycholic acid (DOCA) conjugate (HD) as drug carrier was reported here. As the surface was negatively charged, this micelle could resist serum adsorption, showing favorable stability. Moreover, fluorescence observation confirmed that it was able to deliver model hydrophobic drug doxorubicin (DOX) into HeLa cells efficiently. The DOX-loaded micelles showed sustained release behavior at pH 7.4, and accelerated release behavior at pH 5.0 or in the presence of ß-glucuronidase, which over-expressed in tumor cells. In vitro cytotoxicity assay demonstrated that the half-maximal inhibitory concentration (IC50) of DOX-loaded micelles against HeLa cells was much lower than that of COS7 cells, showing significant therapeutic distinction between tumor cells and normal cells. Combining with the good biocompatibility and biodegradability of heparosan, this micelle may be promising in clinical application for targeted drug delivery.
Assuntos
Antineoplásicos/química , Dissacarídeos/química , Sistemas de Liberação de Medicamentos , Micelas , Neoplasias , Animais , Antineoplásicos/administração & dosagem , Células COS , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Dissacarídeos/administração & dosagem , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos/métodos , Células HeLa , Humanos , Neoplasias/tratamento farmacológicoRESUMO
OBJECTIVE: To explore a method for in vivo skin reconstruction. METHODS: Thirty Sprague-Dawley (SD) rats were randomly divided into two paired groups, i.e. in vivo culture (A group, 10 pairs) and in vitro grafting (B group, 5 pairs). Skin samples were harvested from the rats of the two groups for the isolation of epithelial cells which were then mixed cultured in vitro in 1:1 ratio. Mixed cellular suspension in A group was harvested 4 days after culture. The mixed cellular sheets were harvested 14 days after culture. The cultured cells and sheets were then transplanted onto total skin loss wounds of donor rats for further cultivation. The wounds in A group were covered with allogeneic full-thickness skin. While the wounds in B group were covered by collagen membrane and gauze. Wound repair was observed and compared between the two groups at 2 - 3 post-operative weeks. RESULTS: Most of the wounds in A group healed after 2 - 3 weeks with smooth surface, and the peithelium connected closely and tightly with the subcutaneous tissue. In the wounds in B group on 5 post-operative day, some of the cellular sheets survived and some fell off. Even the healed wounds in B group would be injured again resulting in protracted small wounds. CONCLUSION: In vivo in situ epithelial culture might be an optional method of skin reconstruction for wound healing.