Adhesion formation after abdominal surgery is a significant cause of post-operative morbidity. In gynecological surgery, adhesions can lead to infertility, chronic pain, and obstructive disorder. Numerous adhesion prevention adjuvant have been investigated, most of which are based on a pharmacological agents or protective barriers. However, no systematic studies have been conducted to determine the combined effect of a transient barrier and pharmacological agent using a local, controlled release system. This provided an incentive to conduct comparative studies on controlled release systems based on unique transient barriers containing previously tested pharmacological agents or potentially effective ones. Phase I objective is to determine the feasibility of using gel-forming, hyaluronic acid/calcium acetate aqueous solution and no aqueous absorbable liquid co polyester as transient barrier matrices to control release of pharmacologically active agents for preventing post-surgical adhesion. Phase I plans entail (1) identifying and synthesizing fast absorbing liquid gel-forming co-polyesters; (2) preparing and conducting comparative rheological studies on hyaluronic acid Ca acetate (HA/CaAc) and liquid copolyesters as candidate matrices for controlled drug release, (3) formulating, the selected (HA/CaAc) and liquid copolyesters with selected pharmacological agents; (4) validating, and conducting a pilot study on three rat models for evaluation of three types of post-surgical adhesion, (5) conducting' the main study and using the results to identify two promising formulations for a Phase II study This will entail (1) completing a comprehensive in vivo studies using three animal species; (2) selecting one final system and completing pertinent development and scale-up studies; and (3) initiating the safety study.
Successful completion of Phase I study will provide the bases for pursuing a Phase II study and eventual development and marketing of a unique, highly effective system for managing key post-surgical complications associated with several procedures. This will not only benefit patients, but also reduce the cost of healthcare.
