RESUMO
Despite promising preclinical results, the clinical benefits of cancer gene therapy have been modest heretofore. The main obstacle continues to be the level and persistence of gene delivery to sufficiently large areas of the tumor. One approach for overcoming this might entail extended local virus release. We studied the utility of silica gel monoliths for delivery of adenovirus to advanced orthotopic gastric and pancreatic cancer tumors. Initially, the biochemical properties of the silica-virus matrix were studied and nearly linear release as a function of time was detected. Virus stayed infective for weeks at +37 degrees C and months at +4 degrees C, which may facilitate storage and distribution. In vivo, extended release of functional replication deficient and also replication-competent, capsid-modified oncolytic viruses was seen. Treatment of mice with pancreatic cancer doubled their survival (P<0.001). Also, silica gel-based delivery slowed the development of antiadenovirus antibodies.
Assuntos
Adenoviridae/genética , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Neoplasias/terapia , Terapia Viral Oncolítica/métodos , Adenocarcinoma/terapia , Animais , Anticorpos Antivirais/análise , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos SCID , Neoplasias Pancreáticas/terapia , Sílica Gel , Dióxido de Silício , Neoplasias Gástricas/terapia , Fatores de TempoRESUMO
The lubrication properties of two commercial-grade magnesium stearates were studied. Their moisture contents and crystal structures were similar. There were minor differences in their fatty acid composition, but the differences did not affect the lubrication properties. The lubrication properties correlated with particle size distributions and specific surface area. The effect of these parameters was further studied with unmilled and milled chemically pure magnesium stearate. Milling decreased the particle size and increased the specific surface area. In both cases, the batch with a smaller particle size and larger specific surface area had considerably better lubricity.
Assuntos
Adjuvantes Farmacêuticos/química , Ácidos Esteáricos/química , Varredura Diferencial de Calorimetria , Fenômenos Químicos , Química Farmacêutica/métodos , Físico-Química , Lubrificação , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Comprimidos/química , Difração de Raios XRESUMO
A new stability-indicating HPLC method that is highly selective for the separation of E and Z isomers of tamoxifen citrate [(Z)-2-[p-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine citrate] is described. The method can be used to assay tamoxifen citrate and the E isomer impurity in both bulk drug and tablets. The chromatographic system consists of a 5-microns octadecyl silica column and a mobile phase composed of an aqueous phosphate buffer (pH 2.0) and acetonitrile. N,N-Dimethyloctylamine is used as an additive in the mobile phase for improving the peak shape of tamoxifen citrate. Compared with the existing official U.S. and British Pharmacopeia methods, the new method offers the following advantages: better resolution between the E and Z isomers, shorter analyses time, stability indication, and a less aggressive mobile phase that results in a longer column life.
