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2.
Pharmaceutics ; 11(1)2019 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-30621141

RESUMO

The present study was carried out to investigate the potential of cationic functionalization on imatinib nanocrystals to improve the mucoadhesiveness and, thus, delivery to the lesion of cervicovaginal tumors. Amino-group-functionalized imatinib nanocrystals (NC@PDA-NH2) were prepared with near-spheroid shape, nanoscale size distribution, positive zeta potential, and relatively high drug content with the aid of the polydopamine-coating technique. Efficient interaction between NC@PDA-NH2 and mucin was proven by mucin adsorption which was related to the positive zeta-potential value of NC@PDA-NH2 and the change in the size distribution on mixing of NC@PDA-NH2 and mucin. Cellular uptake, growth inhibition, and apoptosis induction in cervicovaginal cancer-related cells demonstrated the superiority of NC@PDA-NH2 over unmodified nanocrystals. For practical intravaginal administration, NC@PDA-NH2 was dispersed in Pluronic F127-based thermosensitive in situ hydrogel, which showed suitable gelation temperature and sustained-release profiles. In comparison with unmodified nanocrystals, NC@PDA-NH2 exhibited extended residence on ex vivo murine vaginal mucosa, prolonged in vivo intravaginal residence, and enhanced inhibition on the growth of murine orthotopic cervicovaginal model tumors indicated by smaller tumor size, longer median survival time, and more intratumor apoptosis with negligible mucosal toxicity. In conclusion, cationic functionalization endowed NC@PDA-NH2 significant mucoadhesiveness and, thus, good potential against cervicovaginal cancer via intravaginal administration.

3.
Int J Pharm ; 556: 217-225, 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30557679

RESUMO

Nanocrystals has been constructed for insoluble drugs as a novel type of nanoscale drug delivery systems with high drug loading. How to prepare nanocrystals with good stability and tumor targeting capability is still challenging. This study was to modify paclitaxel nanocrystals with polyethylene glycol (PEG) for stabilization and RGD peptide for tumor targeting. Inspired by the structure of mussel's foot protein, polydopamine (PDA) was introduced to the drug delivery system for the modification of nanocrystals. Briefly, PDA was coated on the surface of nanocrystals to form a reaction platform for further PEGylation and RGD peptide conjugation. PEGylated nanocrystals with RGD peptide modification (NC@PDA-PEG-RGD) were prepared with near-spheroid shape, drug loading 45.12 ±â€¯1.81% and a hydrodynamic diameter 419.9 ±â€¯80.9 nm. The size of NC@PDA-PEG-RGD remained basically unchanged for at least 72 h in the presence of plasma while the size of unmodified nanocrystals (NC) increased and exceeded 1000 nm in 12 h. Cellular uptake and cellular growth inhibition experiments using the lung cancer cell line A549 demonstrated the superiority of NC@PDA-PEG-RGD over NC or PEGylated nanocrystals without RGD modification (NC@PDA-PEG). In A549 model tumor bearing-mice, NC@PDA-PEG-RGD showed significantly higher intratumor accumulation and slower tumor growth than NC@PDA-PEG or free paclitaxel. In summary, our study suggested the superiority of RGDmodified PEGylated paclitaxel nanocrystals as a lung cancer-targeted delivery system and the potential of PDA coating technique for targeting functionalization of nanocrystals.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Oligopeptídeos/química , Paclitaxel/administração & dosagem , Polietilenoglicóis/química , Células A549 , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos , Humanos , Hidrodinâmica , Indóis/química , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas , Oligopeptídeos/administração & dosagem , Paclitaxel/química , Paclitaxel/farmacologia , Tamanho da Partícula , Polímeros/química , Fatores de Tempo
4.
Yao Xue Xue Bao ; 42(8): 803-9, 2007 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-17944225

RESUMO

With the development of molecular biology, genome science becomes an important subject currently. Characterized by high-throughput, high-integration, high-parallelism, miniaturization and automation, it is the integrated study of gene properties on a large scale. Stroke, an important cerebral vascular disease, is one of the threats to human health. The utilization of microarray study for the pathogenesis of stroke, not only reveals the essentials of the disease in the overall level of genes, but also contributes to the detection of therapeutic targets and the development of novel drugs for stroke. Referring to our own work, this discussion focuses on the progress of the mechanisms underlying experimental cerebral ischemia investigation in vivo as well as anti-cerebral ischemia agents by gene chip technology.


Assuntos
Isquemia Encefálica/genética , Perfilação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Traumatismo por Reperfusão/genética , Acidente Vascular Cerebral/genética , Animais , Encéfalo/irrigação sanguínea , Isquemia Encefálica/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica , Humanos , Fator 1 Induzível por Hipóxia/metabolismo , Interleucina-6/metabolismo , Precondicionamento Isquêmico , Neovascularização Fisiológica/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/metabolismo , Acidente Vascular Cerebral/metabolismo
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