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@article{206504,
        author = {AYUSH KUMAR SRIVASTAVA and Ved Prakash Tiwari and Ashish Kumar Srivastav and Bandana Singh},
        title = {Chitosan-Coated Alginate Nanoparticles for Oral Insulin Delivery: Box-Behnken Optimization, pH-Responsive Release, Enzymatic Protection and In Vitro Permeation},
        journal = {International Journal of Innovative Research in Technology},
        year = {2026},
        volume = {13},
        number = {2},
        pages = {1760-1768},
        issn = {2349-6002},
        url = {https://ijirt.org/article?manuscript=206504},
        abstract = {Oral insulin delivery remains limited by acidic gastric conditions, enzymatic degradation, mucus diffusion barriers and low epithelial permeability. This study formulated chitosan-coated calcium alginate nanoparticles as an aqueous, polymeric carrier for improving the in vitro oral delivery potential of insulin. Insulin-loaded nanoparticles were prepared by ionic gelation using sodium alginate, calcium chloride and chitosan. A three-factor, three-level Box-Behnken design evaluated the effects of alginate concentration, chitosan concentration and calcium chloride concentration on particle size, polydispersity index, zeta potential, entrapment efficiency and simulated gastrointestinal release. A desirability-selected formulation containing sodium alginate 1.425 mg/mL, chitosan 0.660 mg/mL and calcium chloride 21.5 mM showed particle size 221.4 ± 3.7 nm, PDI 0.214 ± 0.011, zeta potential +25.7 ± 1.6 mV, entrapment efficiency 78.6 ± 1.2%, drug loading 7.8 ± 0.3% and process yield 74.8 ± 1.5%. The optimized nanoparticles restricted insulin release in simulated gastric fluid to 8.7 ± 0.4% at 2 h and then provided controlled release of 70.3 ± 1.6% at 8 h and 86.1 ± 2.1% at 12 h in intestinal media. Insulin remaining after pepsin exposure in simulated gastric fluid was 88.9 ± 2.4% for nanoparticles compared with 28.6 ± 3.1% for insulin solution. Cumulative permeation at 8 h increased from 19.1 ± 1.4% for insulin solution to 48.6 ± 2.8% for nanoparticles, corresponding to an apparent permeability enhancement of 2.60-fold. These findings support chitosan-coated alginate nanoparticles as a promising in vitro platform for pH-responsive insulin protection and absorption-related enhancement. In vivo pharmacokinetic, pharmacodynamic, safety and insulin-bioactivity studies are required before claims of true oral bioavailability or therapeutic efficacy can be made.},
        keywords = {oral insulin; chitosan; sodium alginate; nanoparticles; ionic gelation; Box-Behnken design; pH-responsive release; in vitro permeation.},
        month = {July},
        }