Among the various systems analyzed, those based on the combination of hemiesters derived from alternating copolymers of maleic anhydride and alkylvinyl ethers of monomethoxyoligoethylene glycols with human serum albumin and iperhydroxylated stabilizers (modified beta-cyclodextrin) turned out to be respondent to the required needs.
Such hybrid combinations of synthetic and natural polymers, with tunable HLB levels, appeared extremely suitable to incorporate peptide and proteic drugs at desirable loads and very versatile to the production of microcaps, according to a simple and novel proprietary procedure set up on purpose on Lab-scale with great feasibility potential for industrial scale transfer. Accordingly microcaps could be obtained easyly to withstand work-up treatments with fairly narrow dimensional distribution, in the range of 100 - 1um and provided of good morphological and physical integrity with a consequent amenability to pharmaceutical processability for injectable dosage forms.
The prepared hybrid mixes as well as any single component and microcaps themselves when submitted both in vivo and in vitro to preliminary toxicology studies resulted substantially safe. A more extensive investigation on this features will be carried out prior to a deep involvement in the exploitation of the results.
Kinetic studies on the release of the active component IFN-alpha or mimicking proteins carried out on microcaps under different conditions, allow to classify the systems as falling in the prolonged release family, with satisfactory life time in the blood stream and maintenance of good antiviral activity levels for the IFN-alpha.
Further indications gained on the capability of the prepared systems in targeting the hepatocyte receptors, make them very attractive for development in a first instance of smart drug delivery systems.
It is however to remark that the results achieved in the present study, offer a fairly broad spectrum of potential applications in areas comprising biomedicine, pharmacy and biotechnology.
Proteic drugs are becoming a very important class of new therapeutic agents, but their use is limited by the rapid clearance they undergo once in the bloodstream. This project is aimed at developing novel polymeric matrices suitable to formulate microcaps delivery systems to direct proteic drugs and, in particular, natural alpha interferon to the hepatocytes of the liver, bone marrow and lungs to improve its therapeutic index and reduction of its therapeutic doses.
Biodegradable or bioerodible polymeric systems with well balanced hydrophilic/hydrophobic character as attainable by direct polymerisation of monomeric precursor or polymer-analogue reactions, are the matrices of choice in that they appear to possess the necessary requirements for loading proteic drugs and address to specific receptor sites.
Further to the preparation of the polymeric systems, a toxicological screening and a selection of the best suited materials will be made to scale up their production and microcaps derived there from and surface modified microcaps to impart for targeting attributes. Successful completion of the project should lead to achievement the of biocompatible polymeric materials for the formulation of proteic drug release devices endowed with limited toxicological side effects and high therapeutic indices.
Funding SchemeCSC - Cost-sharing contracts
SY6 6AX Church Stretton