Project: Size controlled particles of chitosan as mucosal delivery system to induce allergen-specific immune tolerance.

Cationic polymers are polymers bearing cationic charges. This polycationic nature is responsible for their mucoadhesiveness (the process whereby synthetic and natural polymers adhere to mucosal surfaces in the body). If these materials are incorporated into pharmaceutical formulations, active pharmaceutical ingredients (API) captured by phagocytic mucosal cells may be enhanced or the API will be released at the site for an extended period of time. Such polymers have therefore gained interest among pharmaceutical scientists as a mean of improving API delivery by promoting the residence time and contact time of the dosage form with the mucous membranes. _x000D__x000D_Chitosan is a one of the only natural polycationic polysaccharide commercially available. Chitosan exhibits a variety of physicochemical and biological properties resulting in numerous applications. In addition to its lack of toxicity and allergenicity, its biocompatibility, biodegradability and bioactivity make it a very attractive substance for diverse applications as a biomaterial in the pharmaceutical and medical fields. It has been approved by the FDA and chitosan based products are already in use in the medical, cosmetic and pharmaceutical markets._x000D__x000D_Chitosan particulate formulations have the potential to be used for targeted and controlled release of API; however, coupling of mucoadhesive properties to microspheres has additional advantages, like a much more intimate contact with the mucus layer, efficient capture and enhanced bioavailability of the API thanks to a high surface to volume ratio, thus improving the amount of API penetrating the mucosa. Size and shape of this system are important factors to improve the bioavailability (i.e. overcoming enzymatic or adsorption barrier in the case of sublingual administration) and to extend the residence time of API delivery system at the site of API absorption. The control of these characteristics are therefore crucial for industrial applications. Different approaches have been used at lab-scale to obtain micro- and nanostructured chitosan-based particles: chemical processes, thermal processes, reverse micelles, spray-drying. Most of these approaches give good results at lab-scale but, on industrial scale, the majority of these approaches are not able to provide particles with uniform dimension. The particle dimension is not only influenced by the process, but also by the macromolecular characteristics of the chitosan used. Well-controlled and reproducible chitosan molecular weight and degree of acetylation is therefore necessary to process chitosan particles with reproducible size and narrow size distribution from batch to batch. _x000D__x000D_The objective of the PARTIKIT project is to combine the technologies of KitoZyme (KTZ) and EmulTech (EMT) to produce well-controlled mucoadhesive formulations made of chitosan particles. The combination of both technologies will solve a range of problems associated with current API delivery technologies and will enable the design of custom made delivery systems fitted for the specific needs related to sublingual immunotherapy treatment performed by Stallergenes (STG). _x000D__x000D_Sublingual immunotherapy (SLIT) is a non-invasive and efficacious treatment of type I respiratory allergies, both in adults and children. Currently, SLIT relies upon aqueous biological extracts administered directly under the tongue, avoiding the use of needles. STG is presently developing second-generation therapies based on highly purified recombinant allergens. The objective is to develop more effective vaccines using simplified immunization schemes._x000D__x000D_The proposed consortium, consisting of KitoZyme (Belgium, SME), EmulTech (Netherlands, SME), and Stallergenes (France, Industry), presents a unique collection of expertise extremely well suited to the proposed project. _x000D__x000D_KTZ is a leader in the manufacturing of ultra-pure chitosan from vegetal sources according to GMP and dedicated to medical/pharmaceutical applications. The expertise and know-how of KTZ is focused on the production of biopolymers using an innovative and patented technology, starting exclusively from vegetal resources as an alternative to shellfish derived chitosan (known to be prone to allergenicity to a certain extent, not very well appreciated in the medical and pharmaceutical market). _x000D_EMT is specialized in the development of emulsification equipment based on micro channel technology. EMT’s continuous production methods answer to the industry’s highest product demands, e.g. highly monodisperse droplets distributions, no waste, efficient operations, reduce the use of chemicals, etc. _x000D_STG is an European biopharmaceutical laboratory specialising in the treatment by desensitisation of allergy-related respiratory conditions. Stallergenes is currently a world leader in the field of sublingual immunotherapy._x000D__x000D_

Acronym PARTIKIT (Reference Number: 5676)
Duration 01/10/2010 - 31/03/2014
Project Topic The PARTIKIT objective is to develop chitosan particles with controlled characteristics as mucoadhesive carrier for API delivery systems. Mucoadhesive particles with perfectly controlled characteristics is a real market demand for an efficient mucosal delivery system such as sublingual immunotherapy
Project Results
(after finalisation)
The project demonstrated that an innovative continuous process for making microparticles (as required for sublingual immunization by Stallergenes) could be developed with our animal-free ultra-pure chitosan. _x000D_Emultech has managed to design the process and optimized the parameters so that this continuous process could be applied using our chitosan. This result enhances the pharmaceutical relevance of chitosan-based mucoadhesive microparticles in general, and the relevance of the sublingual mucoadhesive microparticles of Stallergenes in particular._x000D__x000D_KitoZyme has worked on the process of manufacturing ultra-pure chitosan with the objective to obtain targets in terms of molecular characteristics (molecular weight and degree of acetylation) independantly from each other. The result is a procedure to modify the degree of acetylation of chitosan without changing the molecular weight._x000D__x000D_Another results is a process for making microparticles by spray-drying, with the optimization of parameters and compositions taht would be suitable for sublingual drug delivery in general._x000D_
Network Eurostars
Call Eurostars Cut-Off 4

Project partner

Number Name Role Country
3 EmulTech BV Partner Netherlands
3 KitoZyme SA Coordinator Belgium
3 Stallergenes Partner France