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Over the past few years, there is a drive toward the fabrication and application of bio-based non-cytotoxic drug carriers. Cellulose nanocrystals (CNCs) have gotten immense research attention as a promising bioderived material in the biomedical field due to its remarkable properties. The delivery of analgesic and anti-inflammatory drug, ketorolac tromethamine (KT) by transdermal route is stipulated herewith to fabricate suitable transdermal therapeutic systems. We have synthesized CNCs from jute fibers and aim to develop a non-cytotoxic polymer-based bionanocomposites (BNCs) transdermal patch, formulated with methylcellulose (MC), chitosan (CH), along with exploration of CNCs for sustained delivery of KT, where CNCs act as nanofiller and elegant nanocarrier. CNCs reinforced MCCH blends were prepared via the solvent evaporation technique. The chemical structure, morphology, and thermal stability of the prepared bionanocomposites formulations were studied by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), TGA, DSC, DMA, and SEM. The In vitro drug release studies were executed using Franz diffusion cells. The BNC patches showed in-vitro cytocompatibility and the drug release study revealed that BNC containing 1 wt% CNCs presented the best-sustained drug release profile. The bioderived CNCs appear to enhance the BNCs drug's bioavailability, which could have a broad prospect for TDD applications. [Display omitted] [ABSTRACT FROM AUTHOR]