The development of adhesions following surgery represents a significant, costly morbidity typically expressed as pain and infertility in the patient. Availability of a reliable method to decrease occurrence of adhesions would constitute a beneficial advance in current surgical practice. However, the efficacy and utility in both open and laparoscopic surgery of currently approved standard adhesion barriers is limited. The goal of the proposed project is a delivery system that allows an initial burst of the anti-adhesion agent, zosteric acid (ZA), followed by a sustained release of the agent. Zosteric acid, a natural product extracted from eelgrass Zostera Marina, shows an extremely low toxicity but effectiveness in preventing adhesion formation of various organisms. It will be directly integrated, along with its nanoparticle-encapsulated form, into a thermo-reversible gel made of Pluronic(R) F-127 and Hydroxyl propyl methyl cellulose, which can then be easily applied in both open and laparoscopic surgeries to prevent adhesion development. The specific tasks include: (1) to successfully scale up the production of highly purified ZA;{(2) to assess the collagen deposition and fibroblast activities of human and mouse fibroblast cells using free form of ZA;(3)} to encapsulate ZA into micro/nanoparticles of a relatively rapid biodegradable polymer, poly(lactide-co-glycolide);(4) following encapsulation, we will first conduct in vitro culture studies to determine viability {of the thermo- reversible gel containing free form and micro/nanoparticle encapsulated ZA and} then in vivo studies. If cell culturing does not provide evidence of cell growth inhibition, we will repeat the encapsulation step utilizing an alternative drug (e.g. rhamnolipids) with the appropriate properties. When tissue culturing provides evidence of cell growth inhibition {and non-cytotoxic}, we will then determine the efficacy of the dual-delivery system in preventing adhesions in a swine model. While not to be included in this project, the next phase, following successful animal results, would be to pursue FDA approval and clinical trials. The proposed tasks have been designed to train and engage a team of a graduate, undergraduate and high school students. The involvement of undergraduate (via Tiered Mentoring) and high school students (via Project Lead the Way) are intended to promote and encourage careers in science, technology and engineering, an on-going effort that the PI has been actively participating in. The graduate student will not only be challenged to conduct research related to biomedicine, but also will be provided the opportunity to mentor underclassmen. Through informal discussion and weekly project meetings with the PIs, attending regional or national scientific meetings, and journal publications, the students trained in traditional chemical and material engineering will be given opportunities to explore the biomedical community. If funded, the proposed project would be one of the first NIH-funded researches in the Department of Chemical and Biomolecular Engineering at The University of Akron, a department on the rise in biomaterial research.
This AREA project is to develop a drug delivery system that allows an initial burst followed with a slow release of an anti-adhesive agent, zosteric acid, for the prevention of surgical adhesions. The Department of Chemical and Biomolecular Engineering at the University of Akron is developing focused research in the area of tissue engineering, drug delivery and biofouling based on an established research area, mainly contributed by PI, in biofouling/antifouling,. The program calls for a strong collaborative effort between our University and regional medical institutes, such as Summa Health System and NEOUCOM, and this AREA grant, if funded, will allow for such collaboration to expand and for the exposure of students to various health related research.
