Intraoral Film Containing Insulin-Phospholipid Microemulsion: Formulation and In Vivo Hypoglycemic Activity Study

Abstract

Non-invasive administration of insulin is expected for better diabetes mellitus therapy. In this report, we developed intraoral preparation for insulin. Insulin was encapsulated into nanocarrier using self-assembly emulsification process. To increase lipophilicity of insulin, it was dispersed in phospholipid resulted in insulin-phospholipid solid dispersion. The microemulsion formula was established from our previous work which contained glyceryl monooleate (GMO), Tween 20, and polyethylene glycol (PEG 400) in a ratio of 1:8:1. To confirm the formation of insulin-phospholipid solid dispersion, PXRD, FTIR spectroscopy, and Raman spectroscopy were performed. Then, the microemulsion was evaluated for droplet size and distribution, zeta potential, entrapment efficiency, physical stability, and Raman spectroscopy. In addition, microemulsion with expected characteristic was evaluated for in vitro release, in vitro permeation, and in vivo activity. The droplets size of ∼100 nm with narrow distribution and positive charge of +0.56 mV were formed. The insulin encapsulated in the oil droplet was accounted of >90%. Water-soluble chitosan seems to be a promising film matrix polymer which also functioned as insulin release controller. Oral administration of insulin microemulsion to healthy Swiss-Webster mice showed hypoglycemic effect indicating the success of this protein against a harsh environment of the gastrointestinal tract. This effectiveness significantly increased by fourfold as compared to free insulin. Taken together, microemulsion seems to be a promising carrier for oral delivery of insulin.

Oral Delivery of Insulin for Treatment of Diabetes: Classical Challenges and Current Opportunities

“…Microemulsions enhance the bioavailability of poorly soluble drugs by maintaining them in molecular dispersion in the gastrointestinal tract and extending the absorption window available in the gastrointestinal lumen. Improved oral delivery of insulin from microemulsion systems have been reported by several authors (Cho and Flynn, 1989;Patel et al, 1991;Kraeling and Ritschel, 1992;Watnasirichaikul et al, 2000Watnasirichaikul et al, , 2002Cilek et al, 2005;Graf et al, 2009;Sharma et al, 2010;Karamanidou et al, 2015;Rachmawati et al, 2015).…”

Nonspherical Nanoparticle Shape Stability Is Affected by Complex Manufacturing Aspects: Its Implications for Drug Delivery and Targeting

“… b) Log D is analogous with log P (partition coefficient), but it provides more specific partition coefficient at different pHs. Selected pH values represent various common physiological pHs, namely circulation system and tissue or both so‐called extracellular‐interstitial (≈7.4), intestinal fluid (6.8), endosomal—endo‐lysosomal or generally so‐called intracellular (5.0; 4.0–6.5), and gastric fluid (1.2);…”

Antibacterial activity of curcumin and its essential nanoformulations against some clinically important bacterial pathogens: A comprehensive review

“…The NPs thus synthesized were bordered by water and stabilized by suitable surfactants 187 . NPs synthesized using this method exhibited anticancer, 188 antidiabetic, 189 hepatoprotective properties, 190 cures Alzheimer's disease, and so on 191 . More future investigations in this area is desired to optimize, fine‐tune, and refine the various synthesis methods in order to achieve greater control on NP size, shape, yield, surface charge, and so on.…”