278 - Drug-eluting Microparticles for Uterine Artery Embolization

Purpose: Uterine artery embolization (UAE) is associated with intense postoperative pain which is only temporarily relieved by intra-arterial local anesthetic administration. To prolong pain relief, this project intends to develop starch-based microparticles with dual functionality: embolization and delayed release of lidocaine.

Materials and Methods: Starch was chemically modified using a cross-linking agent under alkaline conditions and processed into powder that was granulated, dried, and sieved to obtain microparticles suitable for UAE. Microparticles were then incubated with lidocaine solution at room temperature. Loading efficiency was assessed spectrophotometrically after washing away unbound drug with water. In vitro release was studied under physiological-like conditions using saline supplemented with albumin to mimic plasma proteins. Successive eluates were collected and analyzed at 262 nm to establish release kinetics.

Results: Cross-linked starch (CLS) yielded stable 500-850 µm reconstituted microparticles (rm) of appropriate size for UAE. The degree of cross-linking directly influenced drug loading and release behavior. The highest and lowest lidocaine incorporation (respectively 114.4 mg/ml and 58.9 mg/mL of rm) were obtained with 30% and 50% cross-linking (respectively CLS-30 and CLS-50). Lidocaine release of CLS-30 and CLS-50 particles were respectively 10.7 mg/h and 7.2 mg/h. Swelling volumes in water of dry CLS-30 and CLS-50 particles were respectively 5.25 mL/g and 7.5 mL/g

Conclusion: Cross-linked starch microparticles may charge and slowly elute local anesthetics in amount and rate that could result in analgesic effect after uterine artery embolization. Tuning the degree of starch cross-linking allows to control drug loading and release necessary for sustained analgesia. Cross-linked starch microparticles with 30% cross-linking showed the best lidocaine loading and sustained release potential.