Development of innovative technology for accelerating healing of diabetic ulcers and chronic wounds by targeted delivery growth factors and antibiotics
2025-05-16 11:30
Project goal: Improvement the treatment results of diabetic ulcers and chronic wounds by targeted delivery of growth factors and antibiotics to the affected areas
Project description: Diabetic foot ulcers are common cause of amputation of lower extremities, significant morbidity, mortality due to protracted inflammatory process, metabolic diabetic dysregulation, impaired angiogenesis, and immunosuppression. Growth factors regulate inflammatory reactions, stimulate angiogenesis, tissue granulation, formation and remodeling of extracellular matrix. Compared with acute wounds, chronic wounds have deficiency of growth factors, decrease in level of bFGF, PDGF, EGF and TGF-β. However, in clinical setting, exogenous application of growth factors has limitations due to low stability, absorption difficulty through wound surface, and elimination by wound exudation. Despite many clinical studies demonstrating positive effect of topical growth factor application, it is impossible to stimulate healing of chronic wounds, without consideration bioavailability and possibility of their accumulation into wound area than systemic circulation. Selective distribution of growth factors by targeted delivery can provide greatest effect in diabetic wound healing, local high concentration in pathological tissues without affecting healthy organs. For effective use of growth factors for treatment of chronic wounds, artificial delivery systems (scaffolds, nanoparticles, liposomes, polymers) are used. However, most of proposed carriers are not widely used due to complexity of creation, drug binding, high cost, toxicity, immunogenic incompatibility. Proposed creation of cellular transport containers based on autologous erythrocyte ghosts and preclinical study effectiveness of targeted delivery of growth factors to accelerate diabetic wound healing. Targeted transport of growth factors can lead to significant acceleration of diabetic wound healing, significantly reduce dose, toxicity, treatment duration and cost, have significant socio-economic effect. Targeted delivery of promising healing mediators to affected area with protracted inflammatory process and impaired angiogenesis will provide much-needed data and may serve as basis for development of new strategic approaches to treatment of diabetic wounds.
Cellular transport containers for targeted delivery of growth factors and antibiotic will be obtained by encapsulation them into autologous erythrocyte ghosts.
Biopharmaceutical studies of erythrocyte transport containers will be conducted by equilibrium dialysis with determination of association/dissociation constants and dynamic stability in vitro.
Pharmacokinetics study erythrocyte transport containers with growth factors and antibiotic in laboratory animals will be conducted.
Preclinical study of effectiveness of accelerating diabetic wound healing by targeted delivery of growth factors and antibiotic to affected areas in experimental animals will be conducted.
Application for Kazakhstan patent will be submitted.
Reports will be presented at international conferences.
Research results will be published as articles and/or reviews in peer-reviewed scientific publications indexed in Science Citation Index Expanded of WebofScience database and/or having a CiteScore percentile in Scopus database.
Methodology: The inclusion of drugs in autologous erythrocyte ghosts is carried out using the method of hypo osmotic hemolysis, used to obtain transport systems for the targeted delivery of drugs based on autologous erythrocytes. The characteristics of the results obtained are carried out using the database of the contractor's laboratory, including the method of spectrophotometry on the Thermo scientific "Evolution 201" spectrophotometer and the Nazarbayev University database based on the general use of "Core facilities", which favorably affects the speed and quality of the work performed (HPLC, Transmission Electron Microscope (TEM, Jeol JEM-1400 Plus) and Scanning Electron Microscope (SEM, Zeiss Crossbeam 540, confocal laser scanning microscope LSM780, Zeiss fluorescent inverted microscope). A preclinical study of the effectiveness of accelerating the healing of diabetic wounds in experimental animals In vivo is conducted at the vivarium of the National Center for Biotechnology.