RESUMO
We report charge-switching ionic nanocomplexes comprised of glycol chitosan grafted with 2,3-dimethylmaleic acid (DMA) (denoted as 'GCS-g-DMA' hereafter) and a proapoptotic peptide. This system allowed for improved peptide delivery to tumor sites via a mechanism of selective peptide release when the pH was dropped from 7.4 to 6.8.
Assuntos
Antineoplásicos/administração & dosagem , Quitosana/química , Portadores de Fármacos/química , Maleatos/química , Neoplasias/tratamento farmacológico , Peptídeos/administração & dosagem , Animais , Antineoplásicos/uso terapêutico , Feminino , Humanos , Concentração de Íons de Hidrogênio , Melanoma Experimental/tratamento farmacológico , Camundongos , Peptídeos/uso terapêuticoAssuntos
Fármacos Fotossensibilizantes/química , Polissacarídeos/química , Animais , Antracenos/química , Clorofilídeos , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Nus , Microscopia de Fluorescência , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Polietilenoglicóis/química , Porfirinas/química , Espectrometria de Fluorescência , Transplante HeterólogoRESUMO
Polysaccharidic nanogels were fabricated with bovine serum albumin (BSA) and a glycol chitosan (GCS) grafted with functional 3-diethylaminopropyl (DEAP) groups. These nanogels were investigated to evaluate their cellular uptake in HeLa cells and in vivo fate in nude mice tumor model. Unlike free BSA, GCS-g-DEAP/BSA nanogels improved cellular uptake of BSA. Furthermore, this system led to an enhanced blood circulation and a high accumulation of BSA in the tumor site. Our collective results strongly support that GCS-g-DEAP/BSA nanogel is a potential carrier system for high molecular weight proteins.
Assuntos
1-Propanol/química , Aminas/química , Quitosana/química , Sistemas de Liberação de Medicamentos , Soroalbumina Bovina/química , Animais , Bovinos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Feminino , Citometria de Fluxo , Humanos , Camundongos , Camundongos Nus , Modelos Moleculares , Estrutura Molecular , Nanogéis , Neoplasias/tratamento farmacológico , Polietilenoglicóis/química , Polietilenoimina/químicaRESUMO
A novel synthetic nanocomplex was constructed from glycol chitosan (GCS) grafted with 2,3-dimethylmaleic anhydride (DMA) (denoted as 'GCD' hereafter) and lysozyme (isoelectric point=10.9) as a model protein. This is a core-shell supramolecular assemble formed through electrostatic interactions between anionic GCD and cationic lysozyme at a pH 7.4. The pH-sensitivity of the nanocomplexes originates from the dissociation of DMA block from GCD at a slightly acidic pH (i.e., pH 6.8), resulting in an increased electrostatic repulsion between cationic GCS and cationic lysozyme. This pH-induced charge switching of GCD provides a mechanism for triggered protein drug release from the nanocomplexes triggered by the small change in pH (pH 7.4-6.8).
Assuntos
Portadores de Fármacos/química , Muramidase/administração & dosagem , Nanopartículas/química , Polímeros/química , Quitosana/química , Cromatografia Líquida de Alta Pressão , Portadores de Fármacos/síntese química , Composição de Medicamentos , Concentração de Íons de Hidrogênio , Anidridos Maleicos/química , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Polímeros/síntese química , Solubilidade , Eletricidade Estática , Propriedades de SuperfícieRESUMO
In this study, a novel pH-responsive nanogel composed of glycol chitosan (GCS) grafted with functional 3-diethylaminopropyl (DEAP) groups (denoted as GCS-g-DEAP hereafter) was fabricated. The GCS-g-DEAP was designed to have a self-assembled arrangement consisting of hydrophilic block (GCS) and hydrophobic block (DEAP) at physiological pH. As the pH decreased to tumor extracellular pH (pH(e)), the nanogel was destabilized due to the protonation of DEAP. The pH-responsive property of the nanogel at tumor extracellular pH (pH(e)) was characterized in drug-release kinetic studies. The release of doxorubicin (DOX) from DOX-loaded nanogels was significantly accelerated at lower pH values, which allowed for increased DOX uptake by non-small lung carcinoma A546 cells under a slightly acidic pH condition, as in tumor pH(e).
Assuntos
Aminas/química , Quitosana/análogos & derivados , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/metabolismo , Polietilenoglicóis/química , Polietilenoimina/química , Linhagem Celular Tumoral , Quitosana/química , Doxorrubicina/farmacologia , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Nanogéis , Tamanho da Partícula , SoluçõesRESUMO
Medical applications of nanoparticular systems have attracted considerable attention because of their potential use in therapeutic targeting of disease tissues and their lower level of toxicity against healthy tissue, relative to traditional pharmaceutical drugs. The use of nanoparticular systems has been shown to overcome the limitations of most anticancer drugs in clinical applications. In particular, the improved performance of smarted nanoparticular system for solving the drug resistance problems that typically interrupt tumor treatment has provided a promising strategy for successful tumor chemotherapy. This review highlights recent studies that have examined the therapeutic effect of nanoparticular systems on drug-resistant tumors and presents insight on how they work.
