Design and Evaluation of Chitosan‐Coated Liposomal Microneedle Capsules for Oral Insulin Delivery: A Proof of Concept

The study presents a proof‐of‐concept for novel protein drug delivery system by formulating layer‐coated liposomes with chitosan oligosaccharide (COS) and insulin, infused in dissolvable microneedles (DMNs), and packed in an enteric‐coated capsule for oral delivery of insulin. Cellular uptake studies using CCD841 showed time‐dependent internalization, while cytotoxicity assays confirmed over 80% cell viability, indicating biocompatibility. The fabricated hydroxypropyl methylcellulose (HPMC) and Aloe vera (AV) based DMN had a pyramidal shape with a height of 464.25 ± 1.48 µm. Permeability studies revealed a sustained release profile in SIF for both layer‐coated liposomes (80.08% ± 3.02) and DMN‐containing layer‐coated liposomes (75.06% ± 1.06). In contrast, a burst release in SGF for layer‐coated liposomes and for DMNs is attributed to charge interactions and polymer solubility. Enteric‐coated capsules demonstrated no insulin release in SGF for 1 h, indicating effective gastric protection. The release for an enteric‐coated capsule containing DMN infused with layer‐coated liposomes in SIF reached 79.24% ± 1.22, mirroring the release profile of DMNs. This multilayered system effectively protects insulin from gastric degradation, facilitates delivery of insulin to the intestine, and achieves a sustained release profile, offering a promising strategy for oral insulin delivery.