RESUMEN
Modifications to the surface chemistry, charge, and hydrophilicity/hydrophobicity of nanoparticles are applicable approaches to the alterations of the in vivo fate of intravenously administered nano-sized drug carriers. The objective of this study is to investigate the in vitro and in vivo antitumor efficacies of curcumin PLGA nanoparticles in relation to their surface structural modification via self-assembling coating with unique fungal hydrophobin. The hydophobin-coated curcumin PLGA nanoparticles (HPB PLGA NPs) were obtained by simply soaking curcumin-loaded PLGA nanoparticles (PLGA NPs) in aqueous fungal hydrophobin solution. The in vitro drug release behavior of the HPB PLGA NPS was also tested. The cytotoxicity and cellular uptake of these nanoparticles were determined in HepG2, A549, and Hela cell lines using MTT assay method and CLSM observation. The in vivo antitumor activity was evaluated in Hela tumor xenografted mice model. Compared with the PLGA NPs, the size and zeta potential of the nanoparticles were changed after hydrophobin coating, whereas similar in vitro release pattern was observed. The pharmacodynamics study showed prolonged blood retention of both nano-formulations than that of free curcumin, but no significant difference between the hydrophobin coated and uncoated nanoparticles. It was found that HPB PLGA NPs had increased cytotoxicities, higher cellular uptake, and improved antitumor efficacy. Surface modification of nanoparticles via self-assembling of hydrophobin is a convenient and promising method of changing particle surface physiochemical properties and antitumor performances. Further investigations, especially on tissue distribution, were needed to assess the potential application of the hydrophobin self-assembling coating in nano-drug delivery carriers.
Asunto(s)
Antineoplásicos/química , Curcumina/química , Hongos/química , Nanopartículas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Células A549 , Animales , Antineoplásicos/farmacología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Curcumina/farmacología , Portadores de Fármacos/química , Portadores de Fármacos/uso terapéutico , Células HeLa , Células Hep G2 , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacología , Ratas , Ratas Sprague-Dawley , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
A simple and sensitive HPLC-MS/MS method was developed and validated for the simultaneous determination of decitabine and valdecitabine in rat plasma. The analytes were separated on a C(18) column (150mm×4.6mm, 3.5µm) and a triple-quadrupole mass spectrometer equipped with an electrospray ionization (ESI) source was applied for detection. A clean solid-phase extraction procedure with cation exchange cartridge was employed to extract the analytes from rat plasma with high recovery of decitabine (>82%). The calibration curves were linear over a concentration range of 10-10,000ng/mL for decitabine and 5-500ng/mL for valdecitabine. The lower limit of quantitation (LLOQ) of decitabine and valdecitabine was 10 and 5ng/mL, respectively. The intra-day and inter-day precisions were less than 15% and the relative error (RE) was all within ±15%. The validated method was successfully applied to a pharmacokinetics study in rats after either decitabine or valdecitabine orally administrated to the Sprague-Dawley rats.