ALGINATES AS DRUG CARRIERS - COVALENT ATTACHMENT OF ALGINATES TO THERAPEUTIC AGENTS CONTAINING PRIMARY AMINE GROUPS

We have been developing a new generation of alginate drug delivery sys tems based on covalent attachment of therapeutic agents to this macrom olecular carrier. This approach involves covalent coupling of the ther apeutic agent either directly through its primary amine group, or via a linker terminating in a primary amine group, to propylene glycol alg inate. A model immunogenic peptide was synthesised and bound directly to alginate, and the effect of conjugation on its immunogenicity was a ssessed. We found that conjugation to alginate resulted in a 4-fold de crease in the humoral antibody response to the peptide following repea ted systemic administration to mice. A conjugate of alginate and 5-ami nosalicylic acid (5ASA) was also prepared. 5ASA was first coupled to a linker (6-aminohexanamide-L-phenylalanine) specifically designed to b e cleaved by the enzyme alpha-chymotrypsin, and subsequently bound to alginate. In vitro release studies showed that 5ASA was gradually rele ased from this conjugate in the presence of alpha-chymotrypsin (48% re leased/24 h), and that the initial rate of drug release was approx. 6- fold slower than that from the low molecular weight analogue, 6-aminoh exanamide-L-phenylalanyl-5ASA.