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AAPS PharmSciTech ; 17(3): 640-51, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26292931


Pure glyceryl mono-oleate (GMO) (lipid) and different batches of GMO commonly used for the preparation of GMO-chitosan nanoparticles were characterized by modulated differential scanning calorimetry (MDSC), cryo-microscopy, and cryo-X-ray powder diffraction techniques. GMO-chitosan nanoparticles containing poloxamer 407 as a stabilizer in the absence and presence of polymers as crystallization inhibitors were prepared by ultrasonication. The effect of polymers (polyvinyl pyrrolidone (PVP), Eudragits, hydroxyl propyl methyl cellulose (HPMC), polyethylene glycol (PEG)), surfactants (poloxamer), and oils (mineral oil and olive oil) on the crystallization of GMO was investigated. GMO showed an exothermic peak at around -10°C while cooling and another exothermic peak at around -12°C while heating. It was followed by two endothermic peaks between 15 and 30 C, indicative of GMO melting. The results are corroborated by cryo-microscopy and cryo-X-ray. Significant differences in exothermic and endothermic transition were observed between different grades of GMO and pure GMO. GMO-chitosan nanoparticles resulted in a significant increase in particle size after lyophilization. MDSC confirmed that nanoparticles showed similar exothermic crystallization behavior of lipid GMO. MDSC experiments showed that PVP inhibits GMO crystallization and addition of PVP showed no significant increase in particle size of solid lipid nanoparticle (SLN) during lyophilization. The research highlights the importance of extensive physical-chemical characterization for successful formulation of SLN.

Química Farmacêutica/métodos , Lipídeos/análise , Lipídeos/química , Nanopartículas/análise , Nanopartículas/química , Varredura Diferencial de Calorimetria/métodos , Fenômenos Químicos , Microscopia Eletrônica de Transmissão/métodos , Difração de Raios X/métodos
AAPS PharmSciTech ; 16(1): 98-107, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25190362


The relapse of cancer after first line therapy with anticancer agents is a common occurrence. This recurrence is believed to be due to the presence of a subpopulation of cells called cancer stem cells in the tumor. Therefore, a combination therapy which is susceptible to both types of cells is desirable. Delivery of this combinatorial approach in a nanoparticulate system will provide even a better therapeutic outcome in tumor targeting. The objective of this study was to develop and characterize nanoparticulate system containing two anticancer agents (cyclopamine and paclitaxel) having different susceptibilities toward cancer cells. Both drugs were entrapped in glyceryl monooleate (GMO)-chitosan solid lipid as well as poly(glycolic-lactic) acid (PLGA) nanoparticles. The cytotoxicity studies were performed on DU145, DU145 TXR, and Wi26 A4 cells. The particle size of drug-loaded GMO-chitosan nanoparticles was 278.4 ± 16.4 nm with a positive zeta potential. However, the PLGA particles were 234.5 ± 6.8 nm in size with a negative zeta potential. Thermal analyses of both nanoparticles revealed that the drugs were present in noncrystalline state in the matrix. A sustained in vitro release was observed for both the drugs in these nanoparticles. PLGA blank particles showed no cytotoxicity in all the cell lines tested, whereas GMO-chitosan blank particles showed substantial cytotoxicity. The types of polymer used for the preparation of nanoparticles played a major role and affected the in vitro release, cytotoxicity, and uptake of nanoparticles in the all the cell lines tested.

Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Nanocápsulas/química , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Difusão , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Humanos , Masculino , Nanocápsulas/administração & dosagem , Nanocápsulas/ultraestrutura , Células-Tronco Neoplásicas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/química , Tamanho da Partícula , Neoplasias da Próstata/patologia , Resultado do Tratamento , Alcaloides de Veratrum/administração & dosagem , Alcaloides de Veratrum/química