Covalently crosslinked hyaluronan-polygalacturonic acid polymer as the drug carrier and its application in surgery

摘要

The composite material based on the hyaluronan (HA) and polygalacturonic acid (PGA) was synthesized for tissue anti-adhesion. HA and PGA were cross-linked covalently by disulfide bonds through thiol oxidation reaction. HA and PGA were grafted with cysteine to yield thiolated HA (HA_(cys), with thiol content of 337 ± 72 umol/g) and PGA (PGA_(cys), with thiol content of 752 ± 77 umol/g), respectively. A HA_(cys)-PGA_(cys) film was fabricated under physiological conditions, with gel content of 84.8 ± 1.7 % and water content of 46.9 ± 2.2 %. The HA_(cys)-PGA_(cys) film was used as the anti-inflammatory drug (rosmarinic acid (RA)) carrier to prevent postsurgical adhesion. The in vitro dynamic release behavior of RA from the HA_(cys)-PGA_(cys) film was analyzed. The RA-entrapped film displayed release profile with an initial burst about 80 % of loaded RA in the early stage. The late phase release of RA from the HA_(cys)-PGA_(cys) film after 24 h followed the zero order (R~2 = 0.978). Animal implant studies of the HA_(cys)-PGA_(cys) and HA_(cys)-PGA_(cys) with rosmarinic acid (HA_(cys)-PGA_(cys)/RA) films reduced adhesion incidences by 83 and 92 %,respectively. To evaluate the efficiency of a combination of physical barriers and an RA anti-inflammatory drug, white blood cell counts from histological sections was done on day 3 after surgery. The results showed that the number of WBCs in the section with the HA_(cys)-PGA_(cys)/RA film decreased by 26.8 % compared with the section with HA_(cys)-PGA_(cys) film. The newly developed HA_(cys)-PGA_(cys) composite polymer showed great potential as the drug carrier and also for postoperative adhesion prevention.