pectins and glycyl-histidyl-lysine

Hydrogels based on natural and modified polysaccharides represent growing group of suitable matrices for the construction of effective wound healing materials. Bioactive tripeptide glycyl-l-histidyl-l-lysine and amino acid α-l-arginine are known to accelerate wound healing and skin repair. In this study, hydrogels based on low-methoxyl amidated citrus pectin or flaxseed gum were prepared and used for the transport of these healing agents to the experimental cutting wounds affected by extensive skin damage. Fourier-transform infrared spectroscopy, rheology, differential scanning calorimetry, scanning electron microscopy, swelling and release tests confirmed that these hydrogels differed in structure and physical properties. The cationic tripeptide was found to bind to carboxylic groups in LMA pectin, and the C3OH hydroxyl and ring oxygen O5 are involved in this interaction. The pectin hydrogel showed high viscosity and strong elastic properties, while the flaxseed gum hydrogel was characterised as a viscoelastic system of much lower viscosity. The former hydrogel released the drugs very slowly, while the latter hydrogel demonstrated zero order releasing kinetics optimal for drug delivery. In the in vivo wound healing testing on rats, both polysaccharide hydrogels improved the healing process mediated by the mentioned biomolecules. The tripeptide applied in the hydrogels showed significantly higher healing degree and lower healing time than in the control animals without treatment and when it was applied in an aqueous solution. Despite the absence of a synergistic effect, the mixture of the tripeptide and α-l-arginine in the hydrogels was also quite effective in wound healing. According to histological analysis, complete healing was achieved only when using the tripeptide in the flaxseed gum hydrogel. These observations might have an important prospect in clinical application of polysaccharide hydrogels.

Topics: Animals; Flax; Gingiva; Humans; Hydrogels; Microscopy, Electron, Scanning; Oligopeptides; Pectins; Rats; Skin; Spectroscopy, Fourier Transform Infrared; Wound Healing

Glycyl-L-histidyl-L-lysine-Cu(II) (GHK-Cu(2+))-loaded Zn-pectinate microparticles in the form of hydroxypropyl cellulose (HPC) compression-coated tablets were prepared and their in vitro behavior tested. GHK-Cu(2+) delivery to colon can be useful for the inhibition of matrix metalloproteinase, with the increasing secretion of tissue inhibitors of metalloproteinases (TIMPS),which are the major factors contributing in mucosal ulceration and inflammation in inflammatory bowel disease. The concentration of peptide was determined spectrophotometrically. The results obtained implied that surfactant ratio had a significant effect on percent production yield (1.25 to 1.75 w/w; 72.22% to 80.84%), but cross-linking agent concentration had not. The entrapment efficiency (EE) was found to be in the range of 58.25-78.37%. The drug-loading factor significantly increased the EE; however, enhancement of cross-linking agent concentration decreased it. The release of GHK-Cu(2+) from Zn-pectinate microparticles (F1-F8) in simulated intestinal fluid was strongly affected by cross-linking agent concentration and drug amount (50 mg for F1-F6; 250 mg for F7-F8), but not particularly affected by surfactant amount. Release profiles represented that the microparticles released 50-80% their drug load within 4 h. Therefore, the optimum microparticle formulation (F8) coated with a relatively hydrophobic polymer HPC to get a suitable colonic delivery system. The optimum colonic delivery tablets prepared with 700 mg HPC-SL provided the expected delayed release with a lag time of 6 h. The effects of polymer viscosity and coat weight on GHK-Cu(2+) release were found to be crucial for the optimum delay of lag time. The invention was found to be promising for colonic delivery.

Topics: Cellulose; Colon; Delayed-Action Preparations; Drug Delivery Systems; Growth Substances; Humans; Oligopeptides; Particle Size; Pectins; Spectrophotometry; Tablets, Enteric-Coated