Design and evaluation of propranolol hydrochloride loaded thiolated Zein/PEO electrospun fibrous matrix for transmucosal drug delivery
Abstract
Thiolated polymers have garnered wide attention from researchers on mucoadhesive drug delivery. This work explores the thiolation of zein protein using cysteine amino acid via the EDC crosslinker. The optimization of thiolation and purification have been done and confirmed using Ellman's assay and Raman spectra. The thiolated Zein/PEO polymer blend has been appraised for electrospinning to fabricate fibrous matrices. The extent of thiol modification augmented the mechanical properties and adhesion in rabbit intestinal mucosa. In vitro cytotoxicity evaluations such as direct contact assay, MTT assay, and live dead assay performed in RPMI 2650 cells corroborated the non-cytotoxicity of the fabricated matrices with and without propranolol hydrochloride (PL). Detailed drug release studies were conducted in PBS. Drug release in PBS followed the Korsmeyer Peppas model of release. On treating RPMI 2650 cells with the matrix, F-actin and adherens junctional proteins retained integrity, and consequently, drug permeation would proceed through the transcellular transport mechanism. Transepithelial electrical resistance (TEER) measurement of the RPMI 2650 cell monolayer also supported the transcellular transport mechanism. Ex vivo permeation study through porcine buccal mucosa showed 41.26 ± 0.56% PL permeation within 24 h of study. It validated the competence of the electrospun thiolated Zein/PEO matrix for transmucosal drug delivery.
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