Also, future research into kinetic profiles of the degradation of PCLP and CCLP by MMPs are necessary for optimizing the lifetime of the hydrogel for in-situ drug delivery. Results indicate the pH and Temperature dependent degradation of Engineered Proteins by collagenase require investigation into other degradable sequences as substitutes for current CLS to better improve lifetime in inflammatory conditions. Further, we have demonstrated that the hydrogel is also susceptible to cleavage by collagenases.

Initial studies have prompted iterations of the component protomers. Further proof, through use of MALDI-TOF, was required in order to more precisely characterize fragment identity however, lack of access to current working negative mode MALDI-TOF prohibited precise molecular weight quantification of fragment bands. This conclusion was confirmed by SDS-PAGE of cleaved CCLP. Exposure of CCLP to collagenase, and MMP-1, indicates that each protomer is susceptible to cleavage in the CLS sequences. This important aspect of this responsive material requires susceptibility to relevant proteases, and is the specific subject of the present study. Proteolysis of the protein hydrogel formed by PCLP and CCLP by collagenases will cause exposure of the protomers and release of drug at the site. The two components of the hydrogel, CCLP and PCLP contain repeats of CaM and M13 domains, respectively, which are separated by engineered collagen-like-sequences (CLS). Self-assembly of the protein hydrogel exploits the high affinity and specific interaction between the protein calmodulin (CaM) and its specific binding peptide, M13. Symptoms and signs of dissociative disorders include. PCP is also known as a dissociative drug. PCP belongs to the class of drugs known as hallucinogens and shares qualities with other dissociative drugs. Since inflammation causes acidification and activation of collagenases in the inflamed tissue, we have designed the hydrogel to respond to both of these queues to effectively deliver drug at the site. Phencyclidine (PCP) is a mind-altering drug that may lead to hallucinations (a profound distortion in a person’s perception of reality). The ultimate goal of this project is to develop a novel self-assembling protein-based hydrogel for in situ delivery of NSAIDs at the site of chronic inflammation. Pleiotropic effects from oral administration of anti-inflammatory drugs limit their effectiveness.

Pclp drug