Efficacy and safety of hydrogel microspheres-loaded ropivacaine for improving incision pain

ObjectiveTo evaluate the efficacy and safety of gelatin hydrogel microspheres prepared by microfluidic technique for loading ropivacaine in the treatment of incision pain.

MethodsThe hydrogel microspheres were prepared by microfluidic technique, the methacryloyl gelatin (GelMA) droplets were obtained by coaxial shearing, and then the hydrogel microspheres were obtained by UV curing after cyclic freezing.Ropivacaine was loaded into hydrogel microspheres through coincubation, the surface characteristics of the microspheres were observed with optical microscope and scanning electron microscope, and the release rate in vitro was measured by dialysis.L-929 and SH-SY5Y cells were divided into 0.9% sodium chloride solution control group (Ctr group), hydrogel microsphere group (GelMA group), ropivacaine group (R group), hydrogel microsphere ropivacaine group (Gel-R group), respectively.Cell proliferation and survival were detected by CCK8 method and Calcein/PI live/dead staining method.SD rats were randomly divided into blank control group 2 (Ctr group 2), microsphere group 2 (GelMA group 2), ropivacaine group 2 (R group 2), hydrogel microsphere ropivacaine group 2 (Gel-R group 2).The mechanical pain threshold in behavior was determined with vonfrey method in the incision pain rat models.The incisional tissues of the rat's foot, and hearts, livers, kidneys were harvested to determine histocompatibility by HE staining.

ResultsThe hydrogel microspheres prepared by microfluidic technique had the characteristics of rounded shape, concentrated particle size distribution, and loose and porous structure, which possessed the function of loading and slowly releasing ropivacaine.In the cell experiment, the results of CCK8 method showed that the toxicity of the Gel-R group was lower than that of the group R (P < 0.05).The live/dead staining results showed that during the 5-day culture period, compared with other groups, more dead cells appeared in the R group.Behavior results suggested that the Gel-R group 2 exhibited analgesic effects throughout the entire incision healing process.The HE staining indicated that there was no significant tissue damage or inflammatory response in the tissues at each incision, and no obvious pathological manifestations were observed in the organs.

ConclusionsThe gelatin hydrogel microspheres prepared by microfluidic technique have the properties of regular morphology and complete structure, and they can prolong the action time of ropivacaine and have good biocompatibility in animal models and cell experiments.