Sustained delivery efficiency of curcumin through ZSM-5 nanozeolites/ electrospun nanofibers for counteracting senescence of human adipose-derived stem cells

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.

Journal

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY

Year

2021

Volume

66

ISSN

1773-2247

eISSN

2588-8943

DOI

10.1016/j.jddst.2021.102902

WoS UID

WOS:000719674100002