Design of Polylactide-Based Biodegradable Materials Exhibiting Protease-Triggered Hydrolysis Using Supramolecular Polyrotaxane Structure

摘要

In the biomedical field, implantable biomedical materials, such as carriers for drug delivery system (DDS) and scaffold for tissue engineering, often must be readily decomposed after use for a given purpose. Therefore, the development of biodegradable materials having stimuli-responsive or -triggered decomposition properties is an important challenge for innovation of implantable biomedical materials. Poly(L-lactide) (PLLA) has frequently been used in implantable carriers for DDS and surgical repair materials. However, specific stimuli-responsive degradation or rapid degradation at a desired time of PLLA-based materials was not achieved. Pseudopolyrotaxane (pPRX) and polyrotaxane (PRX), composed of linear polymers and cyclic compounds, have attracted much attention due to their unique physically interlocked supramolecular structures and their corresponding functions.' Recently, we found that linear PLLA and PLLA-PEG-PLLA triblock copolymer could form pPRXs with a-CDs.2"3 In this study, a biodegradable PRX composed of PLLA and a-CDs (LA-PRX) was synthesized (Figure I)4. The dethreading of the a-CDs was prevented by blocking the PLLA chain with bulky end-groups through enzymatically-cleavable peptide linkages. We report on the protease-triggered degradation behavior of LA-PRX. The obtained LA-PRX was not degraded in the absence of papain, but exhibited a higher degradation rate in response to papain, which catalyzed hydrolysis of the peptide bonds.