Epidural Administration of Curcumin-Loaded Polycaprolactone/Gelatin Electrospun Nanofibers for Extended Analgesia After Laminectomy in Rats.

Several clinical studies have reported the analgesic effect of curcumin (Curc) in various situations such as rheumatoid arthritis, osteoarthritis, and postsurgical pain. Therefore, in this work, Curc-loaded electrospun nanofibers (NFs) are designed to evaluate their sustained release on analgesic effect duration in rats after epidural placement via repeated formalin and tail-flick tests. The Curc-loaded polycaprolactone/gelatin NFs (Curc-PCL/GEL NFs) are prepared through an electrospinning technique and introduced to the rat's epidural space after laminectomy. The physicochemical and morphology features of the prepared Curc-PCL/GEL NFs were characterized via FE-SEM, FTIR, and degradation assay. The in vitro and in vivo concentrations of Curc were measured to evaluate the analgesic efficacy of the drug-loaded NFs. Rat nociceptive responses are investigated through repeated formalin and tail-flick tests for 5 weeks after the placement of NFs. Curc had a sustained release from the NFs for 5 weeks, and its local pharmaceutical concentrations were much greater than plasma concentrations. Rat's pain scores in both early and late phases of the formalin test were remarkably decreased in the experimental period. Rat's tail-flick latency was remarkably enhanced and remained constant for up to 4 weeks. Our findings show that the Curc-PCL/GEL NFs can supply controlled release of Curc to induce extended analgesia after laminectomy.

In vitro expansion of human adipose-derived stem cells with delayed senescence through dual stage release of curcumin from mesoporous silica nanoparticles/electrospun nanofibers.

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.

Curcumin-loaded mesoporous silica nanoparticles/nanofiber composites for supporting long-term proliferation and stemness preservation of adipose-derived stem cells.

The present research aims to design and develop a sustained drug release system to support the long-term proliferation of human adipose-derived stem cells (hADSCs) without losing their stemness and entering the cellular senescence through providing typical cell culture conditions. For this purpose, Curcumin-loaded mesoporous silica nanoparticles (CUR@MSNs) incorporated into Poly-ε-Caprolactone/Gelatin (PCL/GEL) hybrid were prepared via blend electrospinning and their impact was evaluated on cell adhesion, viability, proliferation and also the expression of senescence markers and stemness genes after a long-term in vitro culturing. The in vitro release findings proved that the MSNs incorporated into the electrospun nanofibers (NFs) allowed a sustained release of CUR. According to MTT and PicoGreen assays, the significant metabolic activity and proliferation of hADSCs were detected on CUR@MSNs-NFs after 14 and 28 days of incubation. Furthermore, CUR@MSNs-NFs showed better adhesion and spreading of hADSCs compared to other types of NFs. The sustained and prolonged delivery of CUR inhibited the stem cell senescence through the down-regulation of p16INK4A and up-regulation of hTERT. It also led to an increased stemness potency in growing hADSCs on the fibers. These results confirmed that the nanofiber-based sustained drug delivery system might provide a promising approach in designing highly programmable culture platforms to generate sufficient numbers of biologically functional hADSCs for clinical translation.

Recent advances in electrospun nanofiber-mediated drug delivery strategies for localized cancer chemotherapy.

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.