Designing & optimisation of dual Ca²⁺ and SO₄^2- ionic cross-linked sericin/pectin microbeads using response surface...

Ulcerative colitis, a chronic inflammatory condition of the colon, requires precise and targeted treatment, and polysaccharides, with their pH responsiveness and biodegradability, offer an innovative approach for colon-specific drug delivery. This study aims to develop a highly precise drug delivery system with enhanced therapeutic and targeting efficiency for ulcerative colitis, focusing on the preparation, optimisation, and evaluation of dual cross-linked mesalamine-loaded sericin-pectin (D_CLSPs) micro-beads. These beads utilise the pH-responsive and microflora biodegradability properties of polysaccharides for targeted colon delivery, employing the Response Surface Methodology. Formulated via the ionotropic gelation method with divalent cross-linking ions (Ca²⁺ and SO₄^2-), the D_CLSPs were optimised using a Box-Behnken design to assess the impact of the varying drug, pectin, and sericin polymer proportions. The D_CLSPs were evaluated for entrapment efficiency, thermal behaviour, surface morphology, water uptake, swelling, and in-vitro drug release. Results indicated that spherical beads were successfully developed, with encapsulation efficiency ranging from 65.1% to 95.5%, drug loading between 32.5% and 49.9%, bead sizes of 0.75 mm to 0.92 mm, and degrees of swelling from 0.92 to 1.82. Drug release was controlled by both diffusion and swelling mechanisms, as supported by the Higuchi and Korsmeyer-Peppas models. The optimised formulation demonstrated high drug encapsulation efficiency, pH-responsive swelling, and strong adhesion to the colon, ensuring extended retention at the targeted site. Additionally, the incorporation of sericin enhanced the accuracy of Gaussian fitting for particle size distribution. Overall, the dual cross-linked sericin-pectin beads show potential as mucoadhesive carriers for delivering drugs specifically to the colon.