Oral delivery of insulin provides a good alternative because it is non-invasive and patient-friendly. However, multiple challenges affected this route. To overcome barriers for oral delivery of insulin, we aimed to develop a novel insulin-loaded microemulsion system based on snail mucin for oral administration. The strategy in the novel system of using mucin loading insulin into the inner core of prepared water in oil microemulsion to provide sustained released, increased in vivo stability and enhanced drug absorption in the gastrointestinal tract. We report how microemulsion composed of varying ratios of snail mucin and Tween® 80 (1:9-9:1) using oil/water emulsion preparation method influenced insulin performance after oral administration. The results obtained include an encapsulation efficiency of above 70 %; in vitro release was sustained over 10 h and in vivo evaluations in diabetic rat model shows that insulin-loaded microencapsulation effectively reduced blood glucose levels over a period >8 h after oral administration. Therefore, we suggest that the developed formulation for oral insulin can be a promising alternative dosage form for oral protein delivery.

Background: The aim of the study was to evaluate the suitability of triclosan (TCS) and flurbiprofen (FLB) with poly-ε-caprolactone (PCL), chitosan (CS), and Kolliphor® P188 (KP) for possible application in the design of nano-formulations.Results: Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM) revealed the physical characteristics of the various sample compositions without any apparent interaction. The Fourier transform infrared spectroscopy (FTIR)’s spectra of the physical mixtures showed their characteristic absorption bands with broadening and overlapping of bands in some instances, but no appearance of new bands was observed.Conclusion: The study revealed the physical form stability of the evaluated components after the storage period and lack of definite pharmaceutical incompatibility between them. Thus, the selected drugs and excipients could be used for the development of pharmaceutical nano-formulations.

To overcome barriers and improve oral bioavailability of insulin delivery has been a mirage to formulation scientists due to instability of the insulin after oral administration. Microparticle (MP) composed of chitosan and snail mucin was prepared via double emulsion method for oral delivery of insulin. Microparticles were characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy. The encapsulation efficiency (EE) of the insulin-loaded MPs were evaluated. Insulin release behavior was evaluated in acidic and phosphate buffer (pH 1.2 and 7.4) at 37 °C. Bioactivities of insulin-loaded MPs were evaluated in a diabetic animal model after oral administration. The insulin-loaded MPs showed irregular shape with a zeta potential (>29 mV). The encapsulation efficiency and drug loading were >75 and 28 %, respectively. The in vitro release shows >80 % release of insulin over 12 h in a sustained manner. The insulin-MPs significantly reduced blood glucose levels (>50 %) compared to positive control and the effect lasted for over 8 h. This study suggests that insulin-MPs as prepared would be potential carriers for oral delivery of insulin.

In this study, different ratios of mucin-grafted polyethylene-glycol-based microparticles were prepared and evaluated both in vitro and in vivo as carriers for the oral delivery of insulin. Characterization measurements showed that the insulin-loaded microparticles display irregular porosity and shape. The encapsulation efficiency and loading capacity of insulin were >82% and 18%, respectively. The release of insulin varied between 68% and 92% depending on the microparticle formulation. In particular, orally administered insulin-loaded microparticles resulted in a significant fall of blood glucose levels, as compared to insulin solution. Subcutaneous administration showed a faster, albeit not sustained, glucose fall within a short time as compared to the polymeric microparticle-based formulations. These results indicate the possible oral delivery of insulin using this combination of polymers.

The potential enhancement of metformin hydrochloride (MH) loaded in lipid vesicles targeting therapeutic efficacy on alloxan-induced diabetic rats was investigated. This involved lipid vesicles formulated with homogenously distributed nano-sized particles by a novel integrated process of multiple emulsification by membrane and solvent evaporation. The average diameter of the water-in-oil (W₁/O), W₁/O/W₂ emulsion droplets, and lipid vesicles was 192 nm, 52 µm, and 173 nm, respectively. The entrapment yield of metformin hydrochloride (MH) in the prepared lipid vesicles was 40.12%. The metformin hydrochloride-loaded lipid vesicles (MH-LLVs) sustained the release of the entrapped drug over a 12-h period and reduced the plasma glucose level of diabetic rats by 77.4% compared with free MH solution (2-h period and 58.2%, respectively) after one week post-diabetic treatment through oral administration of MH-LLV and the free drug. The remarkable improvement in the biochemical parameters recorded in the MH-LLV-treated animals compared with those that received free MH solutions depicted an enhanced kidney function, liver function, as well as oxidative stress status. Pancreatic histology depicted a pancreas with intralobular ducts (ID) and exocrine secretory acini that characterize an intact pancreas, which suggests the ability of the MH-LLVs to restore pancreatic cells to normal, on a continued treatment. Overall, MH-LLV appears an encouraging extended-release formulation with enhanced bioavailability, sustained release, and improved antihyperglycemic potentials.