Capsaicin cyclodextrin complex enhances mepivacaine targeting and improves local anesthesia in inflamed tissues

Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics LA . Hence, these drugs show less cell permeation and diminished potency. Since the analgesic capsaicin CAP triggers opening of the TRPV1 receptor pore, its combination with LAs could result in better uptake and improved anesthesia. We tested the above hypothesis and report here for the first time the analgesia effect of a two drug combination LA and CAP on an inflamed tissue. First, CAP solubility increased up to 20 times with hydroxypropyl beta cyclodextrin HP amp; 946; CD , as shown by the phase solubility study. The resulting complex HP amp; 946; CD CAP showed 1 1 stoichiometry and high association constant, according to phase solubility diagrams and isothermal titration calorimetry data. The inclusion complex formation was also confirmed and characterized by differential scanning calorimetry DSC , X ray diffraction, and 1H NMR. The freeze dried complex showed physicochemical stability for at least 12 months. To test in vivo performance, we used a pain model based on mouse paw edema. Results showed that 2 mepivacaine injection failed to anesthetize mice inflamed paw, but its combination with complexed CAP resulted in pain control up to 45 min. These promising results encourages deeper research of CAP as an adjuvant for anesthesia in inflamed tissues and cyclodextrin as a solubilizing agent for targeting molecules in drug deliver

An Abraded Surface of Doxorubicin Loaded Surfactant Containing Drug Delivery Systems Effectively Reduces the Survival of Carcinoma Cells

Abstract An effective antitumor remedy is yet to be developed. All previous approaches for a targeted delivery of anticancer medicine have relied on trial and error. The goal of this study was to use structural insights gained from the study of delivery systems and malignant cells to provide for a systematic approach to the development of next generation drugs. We used doxorubicin Dox liposomal formulations. We assayed for cytotoxicity via the electrical current exclusion method. Dialysis of the samples yielded information about their drug release profiles. Information about the surface of the delivery systems was obtained through synchrotron small angle X ray scattering SAXS measurements. SAXS measurements revealed that Dox loading yielded an abraded surface of our Dox liposomal formulation containing soybean oil, which also correlated with an effective reduction of the survival of carcinoma cells. Furthermore, a dialysis assay revealed that a higher burst of Dox was released from soybean oil containing preparations within the first five hours. We conclude from our results that an abraded surface of Dox loaded drug delivery system increases their efficacy. The apparent match between surface geometry of drug delivery systems and target cells is suggested as a steppingstone for refined development of drug delivery systems. This is the first study to provide a systematic approach to developing next generation drug carrier systems using structural insights to guide the development of next generation drug delivery systems with increased efficacy and reduced side effect