[Development of Tripterygium glycosides nano-carries based on "nanoemulsion-gels" and its pharmacodynamics].

The aim of this study is to develop the Tripterygium glycosides nanoemulsion gels and investigate its pharmacodynamics. Oleic acid was used as oil phase, polyoxyethylene castor oil as surfaetant, and 1,2-propanediol as cosurfactant to screen the formula of Tripterygium glycoside nanoemulsion using the pseudo-temary phase diagrams. Then the nanoemulsion gels was prepared. The ICR mouse ears were sensitazated by 7% DNCB, and then were excited by 0.3% DNCB to stimulate the model of mouse chronic dermatitis and eczema. The concentrations of IFN-γ, IL-4 and IL-8 in mouse blood were determined by ELISA. The results showed that Tripterygium glycosides nanoemulsion gels could significantly inhibit the swelling of mouse ears(P < 0.01) and ameliorate the edama and erythema of model mouse ears skin. Also it could significantly decrease the expression of IFN-γ and IL-4 in model mouse blood. Tripterygium glycosides nanoemulsion gels had a good therapeutic effect on mouse model of dermatitis and eczema. It was expected to provide a new and long-acting exterernal preparation for the treatment of dermatitis and eczema.

Cetirizine dihydrochloride loaded microparticles design using ionotropic cross-linked chitosan nanoparticles by spray-drying method.

To control the release rate and mask the bitter taste, cetirizine dihydrochloride (CedH) was entrapped within chitosan nanoparticles (CS-NPs) using an ionotropic gelation process, followed by microencapsulation to produce CS matrix microparticles using a spray-drying method. The aqueous colloidal CS-NPs dispersions with a drug encapsulation efficiency (EE) of <15%, were then spray dried to produce a powdered nanoparticles-in-microparticles system with an EE of >70%. The resultant spherical CS microparticles had a smooth surface, were free of organic solvent residue and showed a diameter range of 0.5~5 µm. The in vitro drug release properties of CedH encapsulated microparticles showed an initial burst effect during the first 2 h. Drug release from the matrix CS microparticles could be retarded by the crosslinking agent pentasodium tripolyphosphate or the wall material. The technique of 'ionotropic gelation' combined with 'spray-drying' could be applicable for preparation of CS nanoparticlesin-microparticles drug delivery systems. CS-NPs based microparticles might provide a potential micro-carrier for oral administration of the freely water-soluble drug--CedH.

Induction of leukotriene B(4) and prostaglandin E(2) release from keratinocytes by protease-activated receptor-2-activating peptide in ICR mice.

Protease-activated receptor-2 (PAR2) has been shown to play a key role in the pathophysiology of itch. However, the precise mechanism of PAR2-mediated itch remains largely unknown. In the present study, we investigated the effects of several agents on the scratching behavior induced by PAR2-activating peptide (SLIGRL-NH2). Pretreatment of experimental animals with tacrolimus or the 5-lipoxygenase inhibitor zileuton significantly reduced SLIGRL-NH2-induced scratching behavior, whereas histamine H(1) receptor antagonist cetirizine or the cyclooxygenase inhibitor indomethacin had little effect. Furthermore, intradermal injection of SLIGRL-NH2 increased cutaneous levels of LTB(4) and PGE(2). In vitro, SLIGRL-NH2 treatment enhanced LTB(4) and PGE(2) release from primary keratinocytes in a concentration-dependent manner. Preincubation of keratinocytes with zileuton resulted in a significant decrease of LTB(4) release and treatment of indomethacin led to a significant decrease of PGE(2) in response to SLIGRL-NH2 stimulation. In addition, SLIGRL-NH2-induced secretion of LTB(4) and PGE(2) was significantly inhibited by tacrolimus, whereas cetirizine had no effect. These results indicate that SLIGRL-NH2 stimulates LTB(4) and PGE(2) release from mouse keratinocytes and that enhancement of LTB(4) and PGE(2) secretion contributes to SLIGRL-NH2-induced scratching behavior in ICR mice.

Long term high frequency stimulation of STN increases dopamine in the corpus striatum of hemiparkinsonian rhesus monkey.

Long term subthalamic nucleus (STN) high frequency stimulation (HFS) can improve most symptoms of Parkinson's disease (PD) patients and decrease the dosage of antiparkinsonian drug such as Madopar. The mechanism of STN HFS for PD still remains elusive. We hypothesize that the level of dopamine (DA) and its metabolites in the corpus striatum is increased after long term STN HFS. The aim of this study was to examine the DA and its metabolites in the extracellular space of corpus striatum in hemiparkinsonian monkeys during long term STN HFS. Four rhesus monkeys were induced to hemiparkinsonian models by injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) through right internal carotid artery. Then two of them were underwent long term right STN HFS for the subsequent microdialysis sessions. Four microdialysis probe cannulas were implanted into bilateral putamen and caudate nucleus respectively. The microdialysis probe was put into the microdialysis probe cannula of bilateral putamen and caudate nucleus. Dialysates of extracellular space in corpus striatum were collected prior to STN HFS, and subsequently 8 h, 1 week, 1 month, 2 months, 8 months and 10 months after STN HFS. The level of DA and its metabolites were determined by high performance liquid chromatography and subthalamic nucleus electrochemical detection (HPLC-ECD). HFS significantly improved PD symptoms of the monkeys. Rotation evoked by apomorphine (APO) disappeared immediately after HFS pulse generator was turned on. The levels of DA and its metabolites in putamen and caudate nucleus of electrode side increased significantly at different time points after stimulation. Long term STN HFS significantly improved symptoms of hemiparkinsonian rhesus monkey, which might be due to the increase of dopamine and/or its metabolites in corpus striatum.

[Changes of amino acids neurotransmitters in striatum of hemi-parkinsonian rhesus monkey after high frequency stimulation of subthalamic nucleus].

OBJECTIVE: To investigate the influence of high frequency stimulation of the subthalamic nucleus on the levels of amino acids neurotransmitters in striatum of hemi-parkinsonian monkeys. METHODS: Two rhesus monkeys were successfully prepared for the subsequent microdialysis sessions. Collecting the dialysate before turning on the pulse generator, and collecting at 1 week, 1, 8 and 12 months after high frequency stimulation of the subthalamic nucleus. The level of Glu, GABA and Tau were determined by high performance liquid chromatography and fluorometric detection (HPLC-FD). RESULTS: After high frequency stimulation (HFS), PD symptoms of monkeys significantly improved. The levels of Glu in putamen and caudate nucleus of electrodes side at 1 week, 1, 8 and 12 months were increased significantly. The levels of GABA in putamen and caudate nucleus of electrodes side at 1 week, 1 month increased significantly compared with before turning on the pulse generator while decreased at 8, 12 months. The level of Tau in putamen and caudate nucleus increased significantly. CONCLUSION: Long-term STN HFS can increase the level of glutamate and taurine, while decrease the level of GABA in putamen and caudate nucleus of electrodes side. It improves symptoms of hemi-parkinsonian rhesus monkey significantly.