ABSTRACT
There is an unmet need for novel therapeutic tools relieving chronic pain. Hydrogen sulfide (H2S) is highly involved in pain processes; however, the development of ideal matrices for sulfide donor compounds remains a great pharmaceutical challenge. We aimed to establish a suitable transdermal therapeutic system (TTS) using the H2S donor diallyl disulfide (DADS) as a model compound. After the preparation of DADS, its solubility was investigated in different liquid excipients (propylene glycol, polyethylene glycol, silicone oil) and its membrane diffusivity was assessed in silicone matrices of different compositions. Drug-releasing properties of DADS-containing patches with different silicone oil contents were determined with Franz and flow-through cells. We found a correlation between the liquid excipient content of the patch and the diffusion rate of DADS. DADS showed the best solubility in dimethyl silicone oil, and the diffusion constant was proportional to the amount of oil above the 3 m/m% threshold value. The 8-day-old patch showed a significantly lower, but better-regulated, drug release over time than the 4-day-old one. In conclusion, the silicone-based polymer matrix developed in this study is suitable for stable storage and optimal release of DADS, providing a good basis for a TTS applied in chronic pain.
ABSTRACT
Transdermal therapeutic systems (TTSs) enable convenient dosing in drug therapy. Modified silicone-polymer-based patches are well-controlled and cost-effective matrix diffusion systems. In the present study, we investigated the substance release properties, skin penetration, and analgesic effect of this type of TTS loaded with low-dose capsaicin. Release properties were measured in Franz diffusion cell and continuous flow-through cell approaches. Capsaicin was detected with HPLC-UV and UV spectrophotometry. Raman spectroscopy was conducted on human skin samples exposed to the TTS. A surgical incision or carrageenan injection was performed on one hind paw of male Wistar rats. TTSs were applied to the epilated dorsal skin. Patches were kept on the animals for 6 h. The thermal hyperalgesia and mechanical pain threshold of the hind paws were detected. Patches exhibited controlled, zero-order kinetic capsaicin release. According to the Raman mapping, capsaicin penetrated into the epidermis and dermis of human skin, where the target receptors are expressed. The thermal pain threshold drop of the operated rat paws was reversed by capsaicin treatment compared to that of animals treated with control patches. It was concluded that our modified silicone-polymer-based capsaicin-containing TTS is suitable for the relief of traumatic and inflammatory pain.
ABSTRACT
Introduction: An important phase in surgical training is gaining experience in real human anatomical situations. When a cadaver is available it may complement the various artificial practice models. However, it is often necessary to supplement the characteristics of the cadavers with a simulation of a tumor. Our objective was to develop an easy-to-create, realistic artificial tumor-mimic model for peripheral lung tumor resection practice. Methods: In our work we injected barium sulphate enriched silicone suspension into 10 isolated, non-fixed lungs of human cadavers, through the puncture of the visceral pleura. Four lesions-apical, hilar and two peripheral-were created in each of ten specimens. After fixation CT scans were obtained and analyzed. The implanted tumor-mimics were examined after anatomical preparation and slicing. Also performed CT-guided percutaneous puncture was also performed to create the lesions in situ in two lungs of human cadavers. Results: Analyzing the CT data of 10 isolated lungs, out of 40 lesions, 34 were nodular (85.0%) and in the nodular group five were spiculated (12.5%). Satellite lesions were formed in two cases (5.0%). Relevant outflow into vessels or airway occurred in five lesions (12.5%). Reaching the surface of the lung occured in 11 lesions (27.5%). The tumor-mimics were elastic and adhered well to the surrounding tissue. The two lesions, implanted via percutaneous puncture, both were nodular and one also showed lobulated features. Conclusion: Our artificial tumor-mimics were easy to create, varied in shape and size, and with percutaneous implantation the lesions provide a model for teaching every step of a surgical procedure.
