RESUMO
Nanogel-based systems loaded with single anticancer drugs display miscellaneous effectiveness in tumor remission, gradually circumventing mutation and resistance in chemotherapy. Hence, the existence of dual-drug delivered nano-sized systems has been contemporaneous with drug development and preceded the conventional-dose chemotherapy. Among outstanding synergistic drug nanoplatforms, thermosensitive copolymer heparin-Pluronic F127 (Hep-F127) co-delivering cisplatin (CDDP) and curcumins (Cur) (Hep-F127/CDDP/Cur) has emerged as a notable candidate for temperature-responsive drug delivery. The procedure was based on the entrapment of curcumin into the hydrophobic core of bio-degradable co-polymer Hep-F127 while the hydrophilic drug CDDP subsequently conjugated to the backbone heparin to form the core-shell structure. The copolymer was characterized by Fourier transform infrared (FT-IR) spectrophotometry, Transmission Electron Microscopy (TEM), and Dynamic Light Scattering (DLS), to corroborate the successful synthesis and via HPLC along with AES-ICP to evaluate the high drug loading along with a controllable release from the nano-gels. A well-defined nano-shell with size in the 129.3 ± 3.8 nm size range could enhance higher the efficacy of the conjugated-CDDP to Hep-F127 than that of single doses. Moreover, the considerable amount of dual-drug released from thermosensitive nanogels between different conditions (pH = 7.4 and pH = 5.5) in comparison to CDDP from Hep-F127 partially indicated the significantly anti-proliferative ability of Hep-F127/CDDP/Cur to the MCF-7 cell line. Remarkably, drug testing in a xenograft model elucidates the intricate synergism of co-delivery in suppressing tumor growth, which remedies some of the problems affecting in cancer chemotherapy.
Assuntos
Cisplatino/química , Curcumina/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Difusão Dinâmica da Luz , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Microscopia Eletrônica de Transmissão , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
INTRODUCTION: Multi-drug nanosystem has been employed in several therapeutic models due to the synergistic effect of the drugs and/or bioactive compounds, which help in tumor targeting and limit the usual side effects of chemotherapy. METHODS: In this research, we developed the amphiphilic Heparin-poloxamer P403 (HSP) nanogel that could load curcumin (CUR) and Paclitaxel (PTX) through the hydrophobic core of Poloxamer P403. The features of HSP nanogel were assessed through Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), differential light scattering (DLS), and critical micelle concentration (CMC). Nanogel and its dual drug-loaded platform showed high stability and spherical morphology. RESULTS: The drug release profile indicated fast release at pH 5.5, suggesting effective drug distribution at the tumor site. In vitro research confirms lower cytotoxicity of HSP@CUR@PTX compared to free PTX and higher inhibition effect with MCF-7 than HSP@PTX. These results support the synergism between PTX and CUR. CONCLUSION: HSP@CUR@PTX suggests a prominent strategy for achieving the synergistic effect of PTX and CUR to circumvent undesirable effects in breast cancer treatment.
Assuntos
Antineoplásicos , Neoplasias da Mama , Curcumina , Nanopartículas , Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Curcumina/química , Portadores de Fármacos/química , Feminino , Heparina/uso terapêutico , Humanos , Nanogéis , Nanopartículas/química , Paclitaxel/química , Paclitaxel/farmacologia , Poloxâmero/uso terapêutico , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Nanosized multi-drug delivery systems provide synergistic effects between drugs and bioactive compounds, resulting in increased overall efficiency and restricted side effects compared to conventional single-drug chemotherapy. In this study, we develop an amphiphilic heparin-poloxamer P403 (HP403) nanogel that could effectively co-load curcuminoid (Cur) and cisplatin hydrate (CisOH) (HP403@CisOH@Cur) via two loading mechanisms. The HP403 nanogels and HP403@CisOH@Cur nanogels were closely analyzed with 1H-NMR spectroscopy, FT-IR spectroscopy, TEM, and DLS, exhibiting high stability in spherical forms. In drug release profiles, accelerated behavior of Cur and CisOH at pH 5.5 compared with neutral pH was observed, suggesting effective delivery of the compounds in tumor sites. In vitro studies showed high antitumor activity of HP403@CisOH@Cur nanogels, while in vivo assays showed that the dual-drug platform prolonged the survival time of mice and prevented tail necrosis. In summary, HP403@CisOH@Cur offers an intriguing strategy to achieve the cisplatin and curcumin synergistic effect in a well-designed delivery platform that increases antitumor effectiveness and overcomes undesired consequences caused by cisplatin in breast cancer treatment.