Rationale for the design of a novel tool for immunotherapy based on an emulsion of glycosaminoglycan

Abstract

In this article, we describe the rationale behind the design of an innovative immunotherapeutic tool designated imunoTM that is an emulsion of microbial, lowmolecular-weight chondroitin sulfate non-covalently bound to pure phosphatidylcholine with vitamin D3 intercalated in the ensuing multi-molecular structure. The rationale for this design derives from the decade-old observation that chondroitin sulfate is the active principle responsible for the immune-stimulatory, anti-cancer properties of cartilage extracts and from the more recent observation that a known immunotherapeutic compound, the Gc protein-derived Macrophage Activating Factor (GcMAF), works as an adjuvant similar, in principle, to the incomplete Freund’s adjuvant. From these premises, we designed an innovative tool that uses an ultrapure, low-molecular-weight chondroitin sulfate, thus overcoming all limitations associated with blood-derived or animal-derived non-ultrapure extracts, at the same time guaranteeing constant sulfation profile and charge density. This novel form of chondroitin sulfate is non-covalently bound to pure phosphatidylcholine in a self-assembly manner that is coherent with the principles of negentropy. Vitamin D3 is then intercalated in this structure that resembles protocells made of a phosphatidylcholine bilayer. Such an association reduces the main side effect of vitamin D3 that is the induction of hypercalcemia, at the same time maximizing its immunotherapeutic potential. In addition, we describe the mechanism of action of this immunotherapeutic tool with particular reference to stimulation of innate immunity through a mechanism shared by adjuvants such as Freund’s adjuvant. Finally, we describe an example of a transdermal delivery system and we discuss possible applications. *Correspondence to: Marco Ruggiero, Silver Spring Sagl, Via Raimondo Rossi 24, Arzo-Mendrisio 6864, Switzerland, Tel: +41 79 230 9283, E-mail: marco.drruggiero@gmail.com