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Alginate-C18 Conjugate Nanoparticles Loaded in Tripolyphosphate-Cross-Linked Chitosan-Oleic Acid Conjugate-Coated Calcium Alginate Beads as Oral Insulin Carrier.

Simple alginate, alginate-stearic acid, and alginate-C18 conjugate nanoparticles and tripolyphosphate-cross-linked chitosan-oleic acid conjugate-coated calcium alginate beads as the vehicle of nanoparticles were designed. Their size, ζ potential, morphology, drug load, drug release, matrix molecular characteristics, mucus penetration, HT-29 cell line cytotoxicity and intracellular trafficking, in vivo blood glucose lowering, and insulin delivery profiles were characterized. Alginate-C18 conjugate nanoparticles were nontoxic. Among all nanoparticle variants, they had reduced size and ζ potential thus enhancing particulate mucus penetration and intracellular trafficking. Their insulin reabsorption tendency was minimized as alginate active COOH/COO- sites were preoccupied with C18. Their loading into coated beads was translated to reduced drug release in simulated gastric phase with nanoparticles being released in the intestinal phase. The combination dosage form increased the blood glucose lowering extent of insulin and blood insulin level compared with nanoparticles or beads alone. Nanoparticles in beads represented a viable approach for oral insulin delivery.