RESUMO
Co-delivery of chemotherapeutic agents using nanocarriers is a promising strategy for enhancing therapeutic efficacy of anticancer agents. The aim of this work was to develop tamoxifen and imatinib dual drug loaded temperature-sensitive liposomes to treat breast cancer. Liposomes were prepared using 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), monopalmitoyl-2-hydroxy-sn-glycero-3-phosphocholine (MPPC), and different surface active agents. The liposomes were characterized for the average particle size, zeta potential, transition temperature, and drug release below and above liposomal transition temperature. The temperature-sensitive liposomes co-encapsulated with tamoxifen and imatinib were investigated for their synergistic activity against MCF-7 and MDA-MB-231 breast cancer cells. The liposomal nanoparticles showed a transition temperature of 39.4 °C and >70% encapsulation efficiency for tamoxifen and imatinib. The temperature-responsive liposomes showed more than 80% drug released within 30 min above transition temperature. Dual drug loaded liposomes showed synergistic growth inhibition against MCF-7 and MDA-MB-231 breast cancer cells. Co-delivery of tamoxifen and imatinib using temperature-sensitive liposomes can be developed as a potential targeting strategy against breast cancer.
Assuntos
1,2-Dipalmitoilfosfatidilcolina/química , Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Mesilato de Imatinib/administração & dosagem , Lipossomos/química , Lisofosfatidilcolinas/química , Tamoxifeno/administração & dosagem , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Humanos , Mesilato de Imatinib/farmacologia , Nanopartículas/química , Tamoxifeno/farmacologia , TemperaturaRESUMO
The aim of the present study was to evaluate the effectiveness of iontophoretic co-delivery of curcumin and anti-STAT3 siRNA using cationic liposomes against skin cancer. Curcumin was encapsulated in DOTAP-based cationic liposomes and then complexed with STAT3 siRNA. This nanocomplex was characterized for the average particle size, zeta-potential, and encapsulation efficiency. The cell viability studies in B16F10 mouse melanoma cells have shown that the co-delivery of curcumin and STAT3 siRNA significantly (p < 0.05) inhibited the cancer cell growth compared with either liposomal curcumin or STAT3 siRNA alone. The curcumin-loaded liposomes were able to penetrate up to a depth of 160 µm inside the skin after iontophoretic (0.47 mA/cm2) application. The in vivo efficacy studies were performed in the mouse model of melanoma skin cancer. Co-administration of the curcumin and STAT3 siRNA using liposomes significantly (p < 0.05) inhibited the tumor progression as measured by tumor volume and tumor weight compared with either liposomal curcumin or STAT3 siRNA alone. Furthermore, the iontophoretic administration of curcumin-loaded liposome-siRNA complex showed similar effectiveness in inhibiting tumor progression and STAT3 protein suppression compared with intratumoral administration. Taken together, cationic liposomes can be utilized for topical iontophoretic co-delivery of small molecule and siRNA for effective treatment of skin diseases.