In vivo evaluation of post-operative pain reduction on rat model after implantation of intraperitoneal PET meshes functionalised with cyclodextrins and loaded with ropivacaine

• Published in: Biomaterials 2019-02, Vol.192, p.260-270
• Main Authors: Chai, Feng, Maton, Mickael, Degoutin, Stephanie, Vermet, Guillaume, Simon, Nicolas, Rousseaux, Christelle, Martel, Bernard, Blanchemain, Nicolas
• Format: Article
• Language: English
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin - chemistry; Anesthetics, Local - administration & dosage; Anesthetics, Local - pharmacokinetics; Anesthetics, Local - therapeutic use; Animals; Colorectal distension; Cyclodextrin polymer; Drug Carriers - chemistry; Drug delivery; Drug Delivery Systems - methods; Drug Liberation; Life Sciences; Male; Pain, Postoperative - drug therapy; Post-operative pain; Prostheses and Implants; Rats; Rats, Sprague-Dawley; Ropivacaine; Ropivacaine - administration & dosage; Ropivacaine - pharmacokinetics; Ropivacaine - therapeutic use; Surgical Mesh; Visceral mesh
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2018.07.032

The avoidance of post-herniorrhaphy pain can be challenging for hernia repair and has the greatest impact on patient's quality of life, health care utilisation and cost to society. Visceral meshes, functionalised with an efficient drug carrier system – hydroxypropyl beta-cyclodextrin polymer (polyHPβCD) coating, were developed to give a prolonged intraperitoneal analgesic drug release. We attempted to evaluate the in vivo pain-relief efficacy of ropivacaine loaded polyHPβCD functionalised polyester meshes in a rat model of visceral pain induced by colorectal distension (CRD). In vivo safety, pharmacokinetic profile and biodegradation were measured via histological analysis and high-performance liquid chromatography, etc. The results confirmed that the polyHPβCD on the functionalised meshes has a high adsorption capacity of ropivacaine and resulted in a sustained drug release in rats after mesh implantation. This was further reaffirmed by an elevated pain threshold (30%) up to 4 days after implantation in the rat CRD model, compared to 1–2 days for non-adapted meshes. Neither polyHPβCD nor the loaded ropivacaine had a major impact on the inflammatory response. This evidence strongly suggests that polyHPβCD functionalised visceral mesh could be a promising approach for post-operative pain control by improving the intraperitoneal drug delivery and bioavailability. [Display omitted]