JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, vol.66, 2021 (SCI-Expanded)
In the present study, ZSM-5 nanozeolite was incorporated into the Poly-epsilon-Caprolactone/Gelatin nanofibers (PCLGEL NFs) for controlled and sustained release of a natural polyphenol, curcumin (CUR) to enhance the prolonged in vitro expansion of human adipose-derived stem cells (hADSCs) without inducing cellular senescence. XRD, FTIR, BET, TGA, FE-SEM, TEM and water contact angle analysis were used to characterize the fabricated nanozeolites and NFs. A study on the drug discharge pattern from the composite CUR@ZSM-5/PCL-GEL electrospun NFs displayed that by loading CUR into the ZSM-5 nanozeolites, the initial burst release was somewhat eliminated, and a sustained and prolonged drug discharge from NFs was obtained. The data set obtained through FE-SEM, LSCM, MTT and PicoGreen assays, qPCR, and western blotting also revealed better cell adhesion and enhanced metabolic activity and proliferation rate for hADSCs cultured on the CUR@ZSM-5/PCL-GEL NFs compared to other types of NFs after 14 and 28 days of incubation. Besides, Utilizing ZSM-5/NFs for sustained and prolonged delivery of CUR not only remarkably reduced the expression levels of p16INK4A, a crucial modulator of cellular senescence but also led to a significant increase in the transcriptional level and activity of hTERT/telomerase and telomere extension, as well as osteoblastic differentiation markers. These findings demonstrated the potential of ZSM-5/NFs for sustained/controlled release of CUR therapeutic molecules in designing a novel platform toward counteracting cellular senescence and achieving sufficient quantities of fresh hADSCs for regenerative medicine applications.