Assuntos
COVID-19 , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Estudos Retrospectivos , SARS-CoV-2Assuntos
Antineoplásicos Hormonais/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Micelas , Neoplasias/tratamento farmacológico , Polímeros/administração & dosagem , Tamoxifeno/administração & dosagem , Animais , Antineoplásicos Hormonais/metabolismo , Humanos , Neoplasias/metabolismo , Polímeros/metabolismo , Tamoxifeno/metabolismoRESUMO
This study was undertaken to develop and investigate the effect of tamoxifen polymer-lipid hybrid nanoparticles (Tmx-PLN) on its oral bioavailability and efficacy in the 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer model. Modified solvent emulsification-evaporation method was optimized to obtain Tmx-PLN, composed of chitosan and lecithin, of 169.66 ± 4.84 nm particle size. The PLN exhibited prolonged in vitro release in phosphate-buffered saline. Further, PLN displayed enhanced oral bioavailability with considerable increase in AUC (1277.46 vs. 585.01 ng/ml · h), pro- longed t½ (27.87 ± 15.62 vs. 10.18 ± 6.5 h) and mean residence time (40.11 ± 25.72 vs. 17.42 ± 12.04 h) in comparison to pure Tmx. In addition, PLN exhibited significantly increased (P < 0.05) antitumor efficacy in DMBA-induced breast cancer model, when administered once in three days in comparison to Tmx daily dosing. This enhancement may be attributed to a probable reduction in Pgp efflux, decreased first-pass metabolism and lymphatic drug transport. Thus, Tmx-PLN exhibited enhanced potential to increase Tmx therapeutic efficacy in chronic treatment of breast cancer.
Assuntos
Portadores de Fármacos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Nanopartículas/química , Tamoxifeno , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Ratos , Ratos Sprague-Dawley , Tamoxifeno/química , Tamoxifeno/farmacocinética , Tamoxifeno/farmacologiaRESUMO
In the present study, tamoxifen-phospholipid complex (TMX-PLC) was developed and evaluated for its impact on solubility and bioavailability of tamoxifen. TMX-PLC was prepared by solvent evaporation method and characterized. FTIR revealed the disappearance of the characteristic peaks of TMX in the complex, which can be due to weakening, removal or shielding by the phospholipid molecule. This phenomenon could be due to packing of TMX in the hydrophobic cavity of phospholipid and being held by van der Waals forces and hydrophobic interactions. This observation was confirmed by DSC and PXRD. TMX-PLC exhibited increased solubility, dissolution rate with decreased distribution coefficient indicating its increased hydrophilicity. Oral bioavailability of TMX and TMX-PLC were evaluated in Sprague-Dawley (SD) rats. TMX-PLC exhibited considerable enhancement in the bioavailability with an increase in Cmax (0.85 vs. 0.40 µg/mL), t1/2 (22.47 vs. 13.93 h), and AUC0-∞ (15.29 vs. 8.62 µg h/mL) with 212.25% relative bioavailability. This enhancement can be attributed to the improvement of the aqueous solubility of the complex and a probable decrease in its extent of intestinal and hepatic metabolism. Thus, phospholipid complexation holds a promising potential for increasing oral bioavailability of TMX.
