betadex and caryophyllene

Evaluate the anti-hyperalgesic effect of the complex containing β-caryophyllene (βCP) and β-cyclodextrin (βCD) in a non-inflammatory chronic muscle pain mice model and investigated its action on superficial dorsal horn of the lumbar spinal cord.. The βCP-βCD complex were prepared and characterized through the DSC, TG/DTG, FTIR, XRD and SEM. The model of chronic muscle pain was induced by two injections of pH4.0 saline (20μL) into left gastrocnemius 5days apart. After confirming hyperalgesia, male mice were treated with βCP-βCD (10 or 20mg/kg; p.o.) or vehicle (saline 0.9%, p.o.) daily for 9days. 1h after, the mechanical hyperalgesia, muscle withdrawal thresholds and motor performance were evaluated. To evaluate the βCP-βCD action on spinal cord, animals induced with chronic muscle pain were treated with βCP-βCD (20mg/kg; p.o.) or vehicle (saline 0.9%, p.o.) and 90min. after, were perfused, the lumbar spinal cord collected, crioprotected, cut and submitted in an immunofluorescence protocol for Fos protein.. The characterization tests indicated that βCP were efficiently incorporated into βCD. The oral treatment with βCP-βCD, at all doses tested, produced a significant (p<0.05) reduction on mechanical hyperalgesia and a significant (p<0.05) increase in muscle withdrawal thresholds, without produce any alteration in force. In addition, βCP-βCD was able to significantly (p<0.05) decrease Fos expression in the superficial dorsal horn.. Thus, βCP-βCD attenuates the non-inflammatory chronic muscle pain in mice and inhibits the Fos expression in the lumbar spinal cord.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Cannabinoids; Drug Therapy, Combination; Gene Expression Regulation; Hyperalgesia; Male; Mice; Polycyclic Sesquiterpenes; Proto-Oncogene Proteins c-fos; Sesquiterpenes; Spinal Cord Dorsal Horn; Treatment Outcome

β-Caryophyllene (BCP), a natural sesquiterpene existing in the essential oil of many plants, has exhibited a wide range of biological activities. However, its volatility and poor water-solubility limit its application in pharmaceutical field. β-Cyclodextrin (β-CD) has intrinsic ability to form specific inclusion complexes with different drugs to enhance their stability, solubility and bioavailability. The aim of this study is to investigate and compare the oral bioavailability and the pharmacokinetics of free BCP and BCP/β-CD inclusion complex after a single oral dose of 50mg/kg on rats. A simple, rapid, and sensitive gas chromatography-mass spectrometry method in selected ion monitoring (GC-MS/SIM) mode was developed on determination of BCP in rat plasma. The in vivo data showed that BCP/β-CD inclusion complex displayed earlier Tmax, higher Cmax and the AUC0-12h was approximately 2.6 times increase than those of free BCP. These results demonstrated that BCP/β-CD inclusion complex has significantly increased the oral bioavailability of the drug in rats than free BCP.

Topics: Administration, Oral; Animals; beta-Cyclodextrins; Biological Availability; Female; Male; Polycyclic Sesquiterpenes; Rats; Rats, Sprague-Dawley; Sesquiterpenes; Solubility