RESUMO
This study aimed to synthesize methoxy polyethylene glycol propionaldehyde (mPEG20,000-ALD) for the preparation of PEGylated nanoliposomal cisplatin. Nanocarriers such as liposomes are developed for a wide range of drug delivery systems. PEG with high molecular weight (Mw) is used to coat the liposomes. In this study, simulated Fourier transform infrared (FTIR) spectra of mPEG-ALD were obtained using density functional theory (DFT) calculations and then compared with actual FTIR spectrum of mPEG20,000-ALD (Mw = 20 kDa). We found that the intensity of C = O stretching vibration at 1,700 cm-1 related to the carbonyl functional group of mPEG20,000-ALD was very weak. The results of DFT calculations of mPEG-ALD showed that by increasing the Mw of mPEG-ALD, the intensity of C = O stretching vibration related to the carbonyl functional group of mPEG-ALD was decreased, so we concluded the hypothesis of decreasing the intensity of C = O stretching vibration at 1,700 cm-1 as a result of increasing the Mw of mPEG-ALD. In vitro release of cisplatin showed that the percentages of released cisplatin from PEGylated nanoliposomal cisplatin and free cisplatin were determined to be 46 ± 2% and 97 ± 3% after 35 h, respectively. Cytotoxicity of free cisplatin and PEGylated nanoliposomal cisplatin was evaluated and related half-maximal inhibitory concentration on human ovarian cancer cell line A2780CP was obtained to be 76.6 ± 3.1 and 46.6 ± 2.3 µg/mL, respectively.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Nanopartículas/química , Polietilenoglicóis/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/síntese química , Cisplatino/química , Relação Dose-Resposta a Droga , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipossomos/síntese química , Lipossomos/química , Estrutura Molecular , Tamanho da Partícula , Polietilenoglicóis/síntese química , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-Atividade , Propriedades de SuperfícieRESUMO
DFT computations were carried out to characterize the (17)Oand (2)H electric field gradient, EFG, in various bisphosphonate derivatives. The computations were performed at the B3LYP level with 6-311++G (d,P) standard basis set. Calculated EFG tensors were used to determine the (17)O and (2)H nuclear quadrupole coupling constant, χ and asymmetry parameter, η. For better understanding of the bonding and electronic structure of bisphosphonates, isotropic and anisotropic NMR chemical shieldings were calculated for the (13)C, (17)O and (31)P nuclei using GIAO method for the optimized structure of intermediate bisphosphonates at B3LYP level of theory using 6-311++G (d, p) basis set. The results showed that various substituents have a strong effect on the nuclear quadrupole resonance (NQR) parameters (χ, η) of (17)O in contrast with (2)H NQR parameters. The NMR and NQR parameters were studied in order to find the correlation between electronic structure and the activity of the desired bisphosphonates. In addition, the effect of substitutions on the bisphosphonates polarity was investigated. Molecular polarity was determined via the DFT calculated dipole moment vectors and the results showed that substitution of bromine atom on the ring would increase the activity of bisphosphonates.
