Random amphiphilic copolymeric sub-micro particles as a carrier shielding from enzymatic attack for peptides and...

The development of peptide drugs and therapeutic proteins is limited by their rapid clearance in liver and other body tissues by proteolytic enzymes, and consequently peptides and proteins are difficult to administer except by injection. There is a growing effort to circumvent these problems by designing strategies to deliver these drugs to specific site of the body. Among them, this peptide carrier presents several advantages for protein therapy including stability in physiological buffer and lack of toxicity. Here, we have been developing a novel bioadhesive polymer matrix that protects entrapped proteins and peptides from degradation by serine protease. Poly(2-lactobionamidoethyl methacrylate-ran-3-acrylamidophenylboronic acid-ran-methoxypolyethylene glycol methacrylate) glycopolymers were synthesized and could self-assemble into the sub-micro particles. The loading capability of insulin, as a drug model, and the insulin release from the particles were assessed. The inhibitory effect of the particles toward trypsin, elastase, and chymotrypsin was evaluated in vitro. Insulin was effectively encapsulated, up to 10%, and could be stained release in vitro. These glycopolymers displayed a strong inhibitory effect toward these exopeptidases. Therefore, novel glycopolymers with excellent inhibitory activity against proteolytic enzymes and reasonable mucoadhesivity might be a useful tool in overcoming the enzymatic barrier to the mucosal delivery (e.g. nasal and buccal) of therapeutic peptides or proteins.