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.