A sniff of a nanotech insulin nasal spray

UV and NMR spectroscopy as well as various other techniques have been used to study the slow release of insulin over a 120-hour period from chitosan nanoparticles based on polyelectrolyte complex formation. The system has potential as a novel drug delivery agent for use in controlling diabetes that might be administered as a nasal spray.

Joung-Pyo Nam, Changyong Choi, Mi-Kyeong Jang, Young-Il Jeong, and Jae-Woon Nah of the Department of Polymer Science and Engineering, at Sunchon National University, in Jeonnam, working with Sung-Hyun Kim at the Regional Office of Kwangju-Chonnam Small and Medium Business Administration, in Gwangju, and Yoonkyung Park of the Department of Biotechnology College of Natural Science, at Chosun University, in Gwang-ju, Korea, have studied insulin-incorporated low-molecularw-weight chitosan nanoparticles based on polyelectrolyte complex formation. The particles they obtained were spherical and approximately 200 nanometres in diameter.

Chitosan is a naturally occurring linear polysaccharide composed of beta-[1-4]-linked 2-acetamido-2-deoxy-D-glucopyranose and 2-amido-2-deoxy-D-glucopyranose. It has been shown to be both biocompatible and biodegradable and as such as been widely studied for its potential as a biomaterial for biomedical research and drug-delivery systems. Specifically, it might be used as a delivery agent to carry therapeutic materials, such as DNA or anionic drug molecules, across nasal or mucosal layers without damaging tissues.

Previous researchers have demonstrated that chitosan can be formed into nanoparticles or polymeric micelles through polyelectrolyte complex formation with protein drugs or vaccines. Indeed, one team has loaded up such nanoparticles with the glucose-controlling hormone insulin for treating diabetes. Now, Nam and colleagues have demonstrated how those nanoparticles might be adapted for nasal delivery of insulin.

The team has prepared insulin-incorporated chitosan nanoparticles using water-soluble chitosan, as opposed to the insoluble form with which they worked previously. Low molecular weight soluble chitosan is a better candidate for drug or DNA delivery not only because of its enhanced aqueous-solubility and but also because of the free-amine groups.

The team has studied the physicochemical properties of their insulin-loaded nanoparticles using a variety of techniques including Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy, tunnelling electron microscopy. UV spectroscopy was used to determine insulin load of the nanoparticles and the content as the protein is released from its nanocarrier. FITC-insulin showed intrinsic absorption peaks between 400 and 550 nm while absorption peaks for free chitosan were negligible in the same range, the team explains.

Proton NMR spectroscopy allowed them to track degradation of the particles and release of insulin. "The ¹H NMR spectra of the nanoparticles indicated that insulin was successively incorporated into nanoparticles through polyelectrolyte complex formation", the team explains.

Dissociation of the particles in which insulin was labelled with fluorescein isothiocyanate (FITC) also allowed them to use UV absorption to follow insulin release. They found that the hormone was continuously released from the nanoparticles over a 120-hour period at all formulations. "Higher insulin content decreased the rate of insulin release from nanoparticles," the researchers explain, which means that these insulin nanocarriers might be a good candidate for an insulin delivery system based on a nasal spray.