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

Abstract

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 (HAcys, with thiol content of 337 ± 72 μmol/g) and PGA (PGAcys, with thiol content of 752 ± 77 μmol/g), respectively. A HAcys–PGAcys film was fabricated under physiological conditions, with gel content of 84.8 ± 1.7 % and water content of 46.9 ± 2.2 %. The HAcys–PGAcys 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 HAcys–PGAcys 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 HAcys–PGAcys film after 24 h followed the zero order (R 2 = 0.978). Animal implant studies of the HAcys–PGAcys and HAcys–PGAcyswith rosmarinic acid (HAcys–PGAcys/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 HAcys–PGAcys/RA film decreased by 26.8 % compared with the section with HAcys–PGAcys film. The newly developed HAcys–PGAcys composite polymer showed great potential as the drug carrier and also for postoperative adhesion prevention.