RESUMEN
Electrospun nanofibers (NFs)-based drug delivery approaches are of particular interest as a hopeful implantable nanoplatform for localized cancer therapy and treating tissue defect after resection, allowing the on-site drug delivery with minimal side effect to healthy cells. To maintain therapeutic concentrations of anticancer molecules for a relatively long time through a combination of burst and sustained drug release mechanisms, a hybrid of polycaprolactone and gelatin (PCL/GEL) was used for co-encapsulation of free curcumin (CUR) and CUR-loaded mesoporous silica nanoparticles (CUR@MSNs) via electrospinning, resulting in a novel drug-loaded nanofibrous scaffold, CUR/CUR@MSNs-NFs. The as-prepared MSNs and composite NFs were characterized via TGA, FTIR, FE-SEM, TEM, and BET. In vitro release profile of CUR from CUR/CUR@MSNs-NFs was examined, and the in vitro antitumor efficacy against MDA-MB-231 breast cancer cells was also evaluated through MTT, scratch assay, DAPI staining, and real-time PCR. The results disclosed that the smooth, bead-free, and randomly oriented CUR/CUR@MSNs-NFs displayed a combination of initial rapid discharge and sustained release for CUR, which led to higher cytotoxicity, lower migration as well as a more pronounced effect on apoptosis induction than CUR-NFs and CUR@MSNs-NFs. The present study illustrated that the dual drug release mechanisms through MSN/NF-mediated drug delivery systems might have a highly hopeful application as a localized implantable scaffold for potential postoperative breast cancer therapy.
Asunto(s)
Curcumina , Nanofibras , Nanopartículas , Curcumina/farmacología , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Dióxido de SilicioRESUMEN
Electrospun nanofibers (NFs) were utilized to realize the dual-stage release of curcumin (Curc) to fully support the attachment, viability and proliferation of adipose-derived stem cells (hADSCs) with a delay in cellular senescence. For this purpose, both free Curc and Curc-loaded mesoporous silica nanoparticles (Curc@MSNs) were integrated into the electrospun polycaprolactone/gelatin (PCL/GEL) nanofibrous scaffolds and characterized via FTIR, BET, FE-SEM and TEM. In vitro drug release results demonstrated strong dual stage-discharge of Curc from the Curc/Curc@MSNs-NFs. Because of the combination of initial rapid release and late extended drug release, hADSCs cultured on the Curc/Curc@MSNs-NFs showed the greatest adhesion, metabolic activity and proliferation rate with a fibroblastic phenotype after 28 days of culture. Besides, a significant reduction in senescence-associated lysosomal α-L-fucosidase (SA-α-Fuc) expression and activity was also measured in hADSCs cultured on the Curc/Curc@MSNs-NFs. Moreover, not only the expression of hTERT in mRNA and protein levels was considerably increased in hADSCs seeded on the Curc/Curc@MSNs-NFs, but also the telomerase activity and telomere length were significantly enhanced in the scaffolds compared to the other types of scaffolds and control group. These results uncovered the potential of the two-stage discharge profile of Curc from Curc/Curc@MSNs-NFs to provide the biofunctionality of long-term cultured hADSCs for efficient stem cell-based regenerative therapies.
Asunto(s)
Tejido Adiposo/citología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Senescencia Celular , Curcumina/administración & dosificación , Liberación de Fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Nanofibras/química , Nanopartículas/química , Animales , Adhesión Celular/efectos de los fármacos , Proliferación Celular , Células Cultivadas , Curcumina/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Gelatina/química , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Ratones , Poliésteres/química , ARN Mensajero/biosíntesis , Dióxido de Silicio/química , Telomerasa/biosíntesisRESUMEN
Nanotechnology empowered localized cancer chemotherapy has indicated a promising performance for targeting and controlled release of anticancer agents over a period of time to eliminate local-regional recurrence of cancers and also to improve the tissue regeneration during/after treatment. Electrospun nanofiber-based implantable drug-delivery systems have been established as one of the most effective approaches for localized cancer treatment, allowing the on-site delivery of anticancer agents and reducing systemic toxicities and side effects to normal cells. The present review aimed to summarize the latest cutting-edge research on applications of electrospun-based systems for local chemotherapy. Meantime, in vitro and in vivo studies conducted using various anticancer agents along with the capability of electrospun nanofibers for combinatorial/synergistic chemotherapy as well as existing challenges and the potential dramatic advances in applying this pioneering approach for clinical transition in localized treatments of cancer is also discussed.
Asunto(s)
Antineoplásicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Nanofibras/química , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Preparaciones de Acción Retardada/química , Humanos , Nanotecnología/métodosRESUMEN
The aim of this study was to evaluate the efficiency of using a natural substance, curcumin, encapsulated in CD44-targeting hyaluronate-polylactide (HA-PLA) nanoparticles (NPs) for the modulation of macrophage polarity from the pro-inflammatory M1 to anti-inflammatory M2 phenotype. For this purpose, the characterization of the NPs was monitored using 1HNMR, FTIR, DLS and FE-SEM. The effects of curcumin-encapsulated HA-PLA NPs on the viability of LPS/IFN-γ stimulated peritoneal macrophages were determined using MTT assay. The cellular uptake of free curcumin and nano-formulated curcumin was assessed using confocal microscopy. Also, the expression levels of iNOS-2 (M1 marker), Arg-1 (M2 marker) and also pro-inflammatory cytokines were measured by real-time PCR. Data showed that the nano-formulated curcumin with spherical shape, an average diameter of 102.5 nm and high cellular uptake was significantly less toxic to peritoneal macrophages. Furthermore, the nano-formulated curcumin effectively indicated a reduction in iNOS-2 and an increase in Arg-1 levels than free curcumin. The change in macrophage phenotype by curcumin-encapsulated HA-PLA NPs could suppress the inflammation in LPS/IFN-γ stimulated macrophages as evidenced by a major reduction in pro-inflammatory cytokines. Conclusively, the results suggested that the curcumin formulation with CD44-targeting HA-PLA NPs might be a promising platform for the treatment of inflammatory diseases.