RESUMO
The drug release profiles of poly(dimer acid-dodecanedioic acid) P(DA-DDDA) copolymer containing 5% adriamycin hydrochloride (ADM) in vitro were evaluated. The biocompatibility of P(DA-DDDA) under mice skin was also evaluated, macroscopic observation and microscopic analysis demonstrated that the copolymer is biocompatible and well tolerated in vivo. Antitumor efficacy of P(DA-DDDA) copolymers containing 5% adriamycin hydrochloride (ADM) implanted subcutaneously in mice bearing Sarcoma-180 tumor exhibited increased volume doubling time (VDT) (31 +/- 1.5 days) compared to plain subcutaneous injection of ADM (7 +/- 0.9 days). The studies suggest that P(DA-DDDA) copolymer as an effective carrier for antineoplastic drug like adriamycin hydrochloride has a very good prospect in the treatment of noumenon tumors.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Ácidos Dicarboxílicos/administração & dosagem , Doxorrubicina/administração & dosagem , Polímeros/administração & dosagem , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Ácidos Dicarboxílicos/química , Ácidos Dicarboxílicos/farmacocinética , Difusão , Doxorrubicina/química , Doxorrubicina/farmacocinética , Composição de Medicamentos/métodos , Implantes de Medicamento , Injeções Subcutâneas , Teste de Materiais , Camundongos , Polímeros/química , Polímeros/farmacocinética , Resultado do TratamentoRESUMO
New unsaturated polyesters of poly(fumaric acid-glycol-dodecanedioic acid) P(FA-GLY-DDDA) copolymers, poly(fumaric acid-glycol-brassylic acid) P(FA-GLY-BA) copolymers, poly(fumaric acid-glycol-tetradecanedioic acid) P(FA-GLY-TA) copolymers and poly(fumaric acid-glycol-pentadecanedioic acid) P(FA-GLY-PA) copolymers were prepared by melt polycondensation of the corresponding mixed monomers: fumaric acid, glycol and one of C(12-15) dibasic acids. The copolymers were characterized by FT-IR, gel permeation chromatography (GPC), and the surface structure of unsaturated polyesters after solidify were studied by atomic force microscopy (AFM). The molecular structure and composition of the unsaturated polyesters were determined by 1H NMR spectroscopy. In vitro studies showed that some of the copolymers are degradable in phosphate buffer at 37 degrees C and have properly drug release rate as drug carriers. The biocompatibility of P(FA-GLY-DDDA) and P(FA-GLY-BA) copolymers under mice skin was also evaluated, macroscopic observation and microscopic analysis demonstrated that the copolymer is biocompatible and well tolerated in vivo. Antitumor efficacy of P(FA-GLY-DDDA) copolymers and P(FA-GLY-BA) copolymers containing 5% adriamycin hydrochloride (ADM) in mice bearing Sarcoma-180 tumor exhibited increased volume doubling time (VDT) (22+/-1.5 days and 24+/-2.5 days) compared to plain subcutaneous injection of ADM (7+/-0.9 days). The antitumor efficacy of injecting P(FA-GLY-DDDA)-ADM inside tumor twice intervened in 22 days exhibited an especially increased cytotoxic effect as revealed by increased VDT (33+/-2.5 days), and the antitumor efficacy of injecting P(FA-GLY-BA)-ADM inside tumor twice intervened in 24 days exhibited an especially increased cytotoxic effect as revealed by increased VDT (35+/-1.5 days). The studies suggested that P(FA-GLY-DDDA) copolymers and P(FA-GLY-BA) copolymers as effective and injectable carriers for antineoplastic drug like adriamycin hydrochloride have a very good foreground in the treatment of noumenon tumor.
Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Sarcoma 180/tratamento farmacológico , Algoritmos , Animais , Fenômenos Químicos , Físico-Química , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Teste de Materiais , Camundongos , Microscopia de Força Atômica , Transplante de Neoplasias , Polímeros/síntese química , Absorção Cutânea/fisiologia , Solubilidade , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier , Análise de Sobrevida , ViscosidadeRESUMO
Poly(dimer acid-brassylic acid) [P(DA-BA)] copolymers and poly(dimer acid-pentadecandioic acid) [P(DA-PA)] copolymers were prepared by melt polycondensation of the corresponding mixed anhydride prepolymers. The copolymers were characterized by Fourier transform infrared (FTIR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), wide angle x-ray powder-diffraction, and thermal gravimetric analysis (TGA). In vitro studies show that all the copolymers are degradable in phosphate buffer at 37 degrees C, and leaving an oily dimer acid residue after hydrolysis for the copolymer with high content of dimer acid. The release profiles of hydrophilic model drug, ciprofloxcin hydrochloride, from the copolymers, follow first-order release kinetics. All the preliminary results suggested that the copolymer might be potentially used as drug delivery devices.
