Pharmaceutical Research and Therapeutic Sciences

ABSTRACT

The quest for a non-invasive insulin delivery system remains a major challenge in pharmaceutical technology, as conventional subcutaneous injections, while effective, often compromise patient compliance due to pain, inconvenience, and safety concerns. This study explores mixed dry reverse micelles (dRMs) incorporated into a self-nanoemulsifying drug delivery system (SNEDDS) as a potential oral insulin platform capable of overcoming enzymatic degradation, poor permeability, and first-pass metabolism. Human recombinant insulin was successfully encapsulated within reverse micelles using Miglyol, Brij, and Span 80 as the lipid–surfactant system, followed by lyophilization to obtain dry micelles, which were re-dispersed into SNEDDS. The optimized formulation displayed a nanoscale particle size of 172 ± 18 nm with a narrow polydispersity index (0.301 ± 0.02) and near-neutral zeta potential (+1.38 mV), indicating good colloidal stability and suitability for intestinal absorption. Characterization studies including FTIR and morphological analysis confirmed successful encapsulation without structural degradation of insulin, while cytotoxicity assays demonstrated high cell viability (>85%), establishing the formulation’s biocompatibility. Functional evaluation revealed significantly enhanced performance, with in vitro diffusion showing a 3.7-fold increase in insulin permeation compared to free insulin and ex vivo goat intestine studies confirming improved mucosal transport. These improvements can be attributed to the nanoscale size enhancing surface area and absorption, protection of insulin from enzymatic degradation, and surfactant-mediated transient permeability enhancement. Collectively, the findings demonstrate that dRMs embedded in SNEDDS provide a stable, safe, and effective carrier system that can address the key challenges of oral insulin delivery. While further in vivo pharmacokinetic and pharmacodynamic studies are required to validate systemic absorption and glycemic control, the present results provide strong preclinical evidence that mixed dry reverse micelles within SNEDDS represent a promising and scalable strategy for developing oral insulin therapies, potentially reducing reliance on injections and significantly improving patient adherence in diabetes management.

Keywords: Oral Insulin Delivery; Mixed Dry Reverse Micelles; Snedds; Nanocarriers; Bioavailability Enhancement; Peptide Drug Delivery; Intestinal Permeability; Diabetes Management