Novel Alginate Oligomer Products for Enhanced Pharmaceutical Delivery Across Mucosal Barriers

AlgiPharma is developing new alginate oligomer-based treatments for respiratory disease, and infection. The mucosal barrier which lines the surface of the airways and gut represents a formidable obstacle to the passage of many types of therapeutic pharmaceuticals. For inhaled and orally administered drugs the mucosal barrier in the lungs and the intestinal tract represents a significant impediment, preventing drug adsorption and subsequent reduced availability of the drug to the relevant tissues. In many chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis, the production of highly viscous mucus presents a further challenge when trying to deliver drugs including antibiotics across this mucus barrier. The underlying idea for this project is to use alginate oligomers to enhance the delivery of pharmaceuticals across these mucosal barriers. Using alginate oligomers to improve the transport of drugs and antibiotics through the mucosal barrier, will also address many of the challenges associated with antibiotic resistance and toxicity. This could have a significant impact on the treatment of infectious diseases, reducing antibiotic toxicity and potentially slowing the acquisition of antimicrobial resistance. Preliminary data aquired before the project suggested that alginate oligomers are able to enhance the movement of nanoparticle therapeutics across the mucosal barrier. Throughout the MucosAlg project we would explore the alginate technology with different classes of pharmaceuticals. The MucosAlg project focused on developing and demonstrating good alginate conjugates and combinations with pharmaceuticals for use in drug delivery applications. A series of antimicrobial drugs were conjugated to the backbone of alginates and tested against strains of bacteria and fungi. This work resulted in two patents and a publication, and the work is being continued in the TARRGET project with many of the same partners. Alginates have also been used to increase the transport of small molecules, namely antibiotics and cystic fibrosis transmembrane conductance regulator (CFTR) drugs through mucus barriers. Antibiotics are routinely hindered by mucus and on top of that bacteria often form biofilm within the mucus presenting an additional barrier for drug delivery. These experiments with antibiotics resulted in one publication. Nanoparticles that are not injected (inhaled) have to pass through a mucus barrier to enter the body. When the nanoparticles have passed through the mucus they also have to undergo endocytosis to enter the cell and optimizing these two properties have been hard. Several inhaled nanoparticle products have failed in clinical trials due to low efficacy. We have demonstrated that nanoparticles coated with alginates are much more readily taken up by cells covered by a mucos layer and thus have increased uptake by more than 10-fold. Various nanoparticles consist of different components and AlgiPharma and partners have explored many different types of particles in the MucosAlg project. We aim to use these results to generate out-licensable deals with pharmaceutical companies.

The project has led to several new discoveries which have so far been presented in scientific articles, on scientific conferences and patented. New knowledge and know-how has been generated by all project partners and collaborators, especially in the field of nanoaparticle-based medicine. The economic and societal outcomes are still being worked on as it requires a large investment to take these discoveries and turn them into medicine.

AlgiPharma together with its research partners are developing new alginate oligomer based treatments for respiratory disease, infections and wound healing. The project consortium already working with AlgiPharma have identified the potential for an exciting range of new applications for the alginate oligomer technology in drug delivery. The main objective of the project is to develop this potential to enhance the delivery of therapeutics across the mucus barrier. For inhaled and orally-administered drugs this mucosal barrier in the lungs and the intestinal tract represents a significant impediment, preventing drug adsorption and subsequent reduced availability of the drug to its target tissue. In many chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), the production of highly viscous mucus presents a further challenge when trying to deliver drugs across this mucus barrier. This affects both the inhaled and oral administration routes. Using alginate oligomers to improve the transport of drugs through the mucus layer, combined with their ability to potentiate the effectiveness of antibiotics, will also address many of the problems associated with drug resistance and toxicity. This could have a significant impact on the treatment of infectious diseases, reducing antibiotic toxicity and indirectly slowing the acquisition of antimicrobial resistance.