K Stashevskaya

Thrombin receptor agonist peptide entrapped in poly(D,L)-lactide-co-glycolide microparticles: Preparation and characterization

Thrombin receptor agonist peptide (TRAP-6) could advantageously replace thrombin in terms of accelerating wound healing being less expensive and more stable. To promote TRAP-6 pharmacological action as a tissue reconstruction stimulator this study investigated its entrapment within poly(D,L)-lactide-co-glycolide (PLGA) microparticles. Due to its low molecular weight and water solubility, TRAP-6 microencapsulated form is expected to be more useful. This paper reports TRAP-6 microencapsulation by a double (w/o/w) emulsion-evaporation technique. TRAP-6 release kinetics were evaluated by both chemical (HPLC) and biological assays in vitro. The results revealed a high level of TRAP-6 sensitivity to physico-chemical events during the microencapsulation. The surface morphology difference between control microparticles (without TRAP-6) and microparticles with entrapped TRAP-6 during in vitro degradation highlighted a particular role of TRAP-6. The results can allow one to optimize the microencapsulation procedure and to encounter a new promising approach to development of biodegradable polymer drug delivery systems for wound healing.

Biodegradable microparticles loaded with thrombin receptor agonist peptide for gastric ulcer treatment in rats

The aim of the current paper was to elaborate an immobilization method of thrombin receptor agonist peptide (TRAP-6) in biodegradable biocompatible poly(d,l)-lactide-co-glycolide (PLGA) microparticles and to demonstrate the effect of the entrapped peptide for tissue repair, namely for a gastric ulcer treatment in rats. TRAP-6 was entrapped in polymer using w/o/w double emulsion-evaporation technique. The morphology of empty and TRAP-6 loaded microparticles was evaluated by light and scanning electron microscopy (SEM). In vitro release kinetics profile of TRAP-6 from microparticles was studied by HPLC. To investigate gastric mucosal protection effect in vivo, TRAP-6-loaded microparticles were administered in a rat stomach after a previous mucosal injury (a gastric ulcer). Microparticles with entrapped TRAP-6 were found to reduce both an inflammation and proliferation phases of wound healing, and thus accelerated tissue repair in rats.

Biodegradable microparticles with immobilized peptide for wound healing

Thrombin receptor agonist peptide (TRAP-6) may be successfully used instead of thrombin to stimulate regeneration of damaged tissues. Thrombin application is limited by its high price, instability, and proin-flammatory effect at high concentrations. Immobilization of TRAP-6 into a matrix based on lactic and glycolic acid copolymer (PLGA) prevents its destruction by peptidases located in the wound and can also provide controlled release of the peptide. PLGA microparticles with the immobilized peptide were prepared by the double emulgation method. The presence of the immobilized peptide increased the porosity of the microparticle surface detected by scanning electron microscopy. Kinetics of the TRAP-6 release was characterized by a dramatic increase in its concentration in buffer solution (pH 7.5) during the first 2 h after the experiment beginning, and the complete release of the peptide after 20 h. An investigation of TRAP-6 destruction by scanning electron microscopy revealed the increase in the microparticle size and surface porosity already after one day of incubation, and the destroyed microparticles were aggregated by the seventh day of the incubation. Thus, peptide immobilization into PLGA microparticles may be employed for elaboration of a prolonged action preparation with the controlled release of the active agent (peptide).