Physicochemical Stability Study of the Morphine-Ropivacaine-Ziconotide Association in Implantable Pumps for Intrathecal Administration.

PURPOSE: This study aimed to investigate the physicochemical stability of morphine-ropivacaine-ziconotide mixtures used in intrathecal analgesia. MATERIALS AND METHODS: Eight mixtures were studied to assess their stability profiles according to the initial drug concentrations used. The solutions obtained were put in implantable pumps and stored at 37 °C over a period of 60 days. Assays were performed using ultra high-pressure liquid chromatography. Turbidity and pH were also measured throughout the study. RESULTS: Results confirmed excellent physicochemical stability for morphine and ropivacaine. Concerning ziconotide, three of the eight mixtures did not show any sign of chemical instability: average concentrations remained constant throughout the 60 days. A decrease of the concentration was observed for the five other mixtures. Moreover, the appearance of a degradation product linked to oxidation confirmed the ziconotide degradation. CONCLUSIONS: All these results are in favor of a physicochemical stable preparation for three of the mixture profiles when stored in implantable pumps at 37 °C up to 60 days. For the five others, the efficacy should decrease over time owing to the degradation of ziconotide. The decrease in kinetics of the ziconotide concentration depends on the mixing profile. One possibility is to adapt the filling intervals according to the profile of the mixture. Finally, the results show the period of stability ensuring maximum analgesic efficacy for the eight mixture profiles studied.

Photobiomodulation by a new optical fiber device: analysis of the in vitro impact on proliferation/migration of keratinocytes and squamous cell carcinomas cells stressed by X-rays.

Photobiomodulation-based (PBM-based) therapies show promising results in mucositis and dermatitis treatment by stimulating wound healing mechanisms such as cell proliferation and migration. The aim of the present study is to investigate the in vitro effects of CareMin650 on the proliferation and migration of two different types of cells, namely cancer and non-cancer cells, with or without X-ray radiation. Study design used PBM through a combination of 0-3-6 J/cm2 doses-with or without X-ray radiation-on the proliferation and migration capabilities of a keratinocyte cell line (HaCaT) and a squamous cell carcinoma line (SCC61). PBM is delivered by a new woven optical fiber device, namely CareMin650 prototype (light emission by LEDs (light-emitting diodes), peak at 660 nm, irradiance of 21.6 mW/cm2). The effectiveness of PBM to increase HaCaT proliferation and migration (with or without X-ray radiation) supports the capability of PBM to favor wound healing. It also highlights that PBM does not provide any anti-radiation effect to previously X-rays radiated SCC (p < 0.001). Such data supports the beneficial effect of PBM delivered by an optical fiber device to heal wounds, without promoting cancer development.