Tiny Porous Nano-Spheres Carry 2 Drugs at Once
A boronic acid-functionalized mesoporous silica nanoparticle-based drug delivery system (BA-MSN) for glucose-responsive controlled release of both insulin and cyclic adenosine monophosphate (cAMP) was synthesized. Fluorescein isothiocyanate-labeled, gluconic acid-modified insulin (FITC-G-Ins) proteins were immobilized on the exterior surface of BA-MSN and also served as caps to encapsulate cAMP molecules inside the mesopores of BA-MSN. The release of both G-Ins and cAMP was triggered by the introduction of saccharides. The selectivity of FITC-G-Ins release toward a series of carbohydrate triggers was determined to be fructose > glucose > other saccharides. The unique feature of this double-release system is that the decrease of FITC-G-Ins release with cycles can be balanced by the release of cAMP from mesopores of MSN, which is regulated by the gatekeeper effect of FITC-G-Ins. In vitro controlled release of cAMP was studied at two pH conditions (pH 7.4 and 8.5). Furthermore, the cytotoxicity of cAMP-loaded G-Ins-MSN with four different cell lines was investigated by cell viability and proliferation studies. The cellular uptake properties of cAMP-loaded FITC-BA-MSN with and without G-Ins capping were investigated by flow cytometry and fluorescence confocal microscopy. We envision that this glucose-responsive MSN-based double-release system could lead to a new generation of self-regulated insulin-releasing devices. _ACSThe ability to release two interacting substances from separate compartments in a nano-delivery system, provides for much longer shelf life and greater potency at the time of delivery. In this case, the payoff will be stop-gap implantable blood glucose regulation.
For long term control of diabetes, working cellular systems that can synthesise their own insulin are preferable to artificial systems. In general, the same principle is valid for all replacement organs and systems.
Replacement parts that can repair themselves, and work in concert with the rest of the body, are preferable to "one trick pony" replacements that too easily give out.
Almost certainly the best use of the Ames nano-spheres will be for genetic therapies to permanently alter gene expression of cells and tissues. But for now, proving the extent of functionality of this delivery system remains important.