RESUMO
In the present study, doxorubicin (DOX) loaded polyethyleneglycol-poly (DL-lactic-co-glycolic acid) micelle as well as composite micelles composed polyethyleneglycol- poly(DL-lactic-co-glycolic acid) (PEG-PLGA) and Pluronic 105 (P105) were constructed. The micelles, with diameter around 106 nm and 85 nm respectively, were prepared by solvent evaporation method. The results showed that the encapsulation of DOX in micelles could significantly enhance its cytotoxicity in a DOX resistant tumor cell line, K562/DOX. The combination of PEG-PLGA and Pluronic further improved both the tumor-suppressive activity and the intracellular accumulation of DOX, indicating that the composite micelles would be potential to reverse the multidrug resistance in tumor cells.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos , Humanos , Células K562 , Micelas , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Poloxâmero , Polietilenoglicóis , Poliglactina 910 , Sais de Tetrazólio , TiazóisRESUMO
Microdialysis coupled with RP-HPLC was used to study the blood pharmacokinetics of pingyangmycin hydrochloride in rabbits. Supelco RP-amide C16 column was adopted for the analysis of pingyangmycin hydrochloride. The data was analyzed with 3P87 program. The calibration curve was linear in the concentration range from 1.04 to 66.56 microg x mL(-1) (r2 = 0.999 4). The in vivo recovery of microdialysis probe was (42.8 +/- 3.4)% (n = 4). The concentration-time curve of pingyangmycin hydrochloride was fitted to two-compartment model. T1/2 alpha and T1/2 beta were 14.9 and 60.3 min, respectively. The method is proved to be accurate, simple and suitable for the pharmacokinetics study of pingyangmycin hydrochloride in rabbits.
Assuntos
Bleomicina/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Microdiálise/métodos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/sangue , Antibióticos Antineoplásicos/farmacocinética , Área Sob a Curva , Bleomicina/sangue , Bleomicina/química , Bleomicina/farmacocinética , Feminino , Injeções Intravenosas , Masculino , Estrutura Molecular , CoelhosRESUMO
The aim of this study is to investigate the expression of matrix metalloproteinase 2 (MMP-2) and the tissue inhibitor of metalloproteinase 2 (TIMP-2) in oral squamous cell carcinoma (OSCC) and adjacent normal tissues, and explore the role of MMP-2 and TIMP-2 in carcinoma metastasis and invasion. Expression of MMP-2 and TIMP-2 was evaluated in 40 cases with semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemical techniques. The values of MMP-2/beta-actin and TIMP-2/beta-actin in OSCC were significantly higher than those in adjacent normal tissues 2 cm and > or = 5 cm from carcinoma tissues (p<0.05). The results of immunohistochemical analysis show that the positive expression of MMP-2 and TIMP-2 protein in tumor tissues (60.0 and 52.5%) was higher than that in adjacent normal tissues 2 cm (30.0 and 22.5%) and 5 cm (22.5 and 25.0%) from cancer tissues, and the difference was significant p<0.05). The expression of MMP-2 and TIMP-2 was related to the differentiation degree of tumor cells, metastatic lymph node status and stage of carcinoma, but not related to the age and gender of patients, or location of the carcinoma. Therefore, MMP-2 and TIMP-2 may play important roles in the invasion and metastasis of OSCC.