ABSTRACT
Objective: To prepare and characterize armodafinil nanocrystals, and investigate its release in vitro. Methods: Anti-solvent precipitation technology was used to prepare the armodafinil nanocrystals. The formulation and preparation process of the armodafinil nanosuspension were optimized by the orthogonal design experiment with the average particle diameter as the evaluation index. The suspension was prepared into nanocrystals by freeze-drying technology. The particle size and the polydispersity coefficient of the armodafinil nanocrystals were measured. The X-ray powder diffraction method was used to investigate the crystal form transition of the armodafinil. The dissolution behavior of the armodafinil nanocrystals and raw substances was investigated and compared with each other by the slurry method. Results: The prepared amodafinil nanocrystals had a quite uniformly distributed particle size around 100 nm. The nanocrystals appeared to be in irregular form. After amodafinil was made into nanocrystals, the solubility and dissolution were significantly improved. The crystal form of amodafinil significantly changed after nanocrystallization. Conclusion: The preparation of a small and uniformly distributed particle size of amodafinil nanocrystals could significantly improve the dissolution performance of amodafinil, which is beneficial to improving the bioavailability of insoluble drugs.
ABSTRACT
Objective: To prepare and characterize the matrine-loaded poloxamer hydrogels and explore their therapeutic effect on chronic eczema in mice. Methods: The matrine hydrogels were prepared with poloxamer 407 and 188 as matrix. The viscoelasticity of the matrine hydrogels was characterized by rheometer. The ear swelling and weight difference were tested, and the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by ELISA method. The histopathological change of mouse ear tissues was examined via HE-staining, and the immunohistochemical examination was performed to detect the protease-activated re-ceptor-2(PAR-2)expression in mouse ear. These assays were performed to investigate the therapeutic effect of matrine hydrogels on chronic eczema in mice. Results: The matrine hydrogels had good fluidity and spreadability, and rapidly formed a transparent, viscous uniform hydrogel at the skin temperature. Compared with the normal group, the ear weight difference and swelling degree were significantly increased(P<0.05)at the 3, 5 and 10 days after the establishment of the chronic eczema model. Compared with the model group, the ear weight difference and swelling degree were reduced significantly in the martrine hydrogel group(P<0.01), and the serum TNF-α and IL-6 level(P<0.01)and the PAR-2 expression in the chronic eczema tissue(P<0.01, P<0.05)were both significantly decreased in the martrine hydrogel group. Conclusion: Martrine hydrogels could inhibit the inflammatory infiltration of dermal layer and the epidermal layer damage caused by chronic eczema, which are expected to be a good topical gel preparation for treating chronic eczema of skin.
ABSTRACT
The traditional systemic treatment of post-traumatic stress disorder (PTSD) requires a long time period for an effect and has obvious side effects. In this study, tetrandrine temperature-sensitive gel (TTG) was prepared for treatment of PTSD in mice by nasal administration. TTG was prepared with poloxamer as matrix, the gelation temperature was suitable (<32 ℃) and the gelation time was short (1.32 min). Rheology experiments demonstrated that TTG has temperature sensitivity. In vivo imaging system of small animals proved that TTG nasal cavity retention time was so long. The cilia toxic test of toad showed that the formulation was safe. Animal experiments were approved by the Ethics Committee of Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations. The mice were randomly assigned into healthy group, model group and TTG group. The PTSD model of mice was established by single prolonged stress (SPS) and foot-shock method to generate anxiety and fear behavior. On the day 0 of TTG administration, SPS model mice were evaluated by the elevated plus maze (EPM). Percentages of open arm entries number (OE), latency of open arm entries (OL) and the residence time of open arm entries (OT) all indicated that the SPS model was successfully established. On the 7th day of TTG administration, TTG increased the OE and OT, decreased the OL of SPS mice. The feard behavior of mice in the foot-shock model was tested using conditioned fear box, 7 days of TTG treatment can reduce the freezing time of the mice obviously. The pathological changes of hippocampus, prefrontal cortex and amygdala were observed by H&E histological sections and c-fos immunohistochemical expression. The main influenced areas of PTSD were revealed to be the CA1 of hippocampus, prefrontal cortex and amygdala. All of the above indicated that TTG is a convenient, safe and effective drug for PTSD treatment, and will provide a new choice for clinical management of PTSD.
ABSTRACT
Topically applied traditional Chinese medicines (TCM) generally show low transdermal rates and doses, leading to weak therapeutic efficacy. Here, cataplasm of white mustard seed varnish was prepared. The effects of iontophoresis and sonophoresis on the transdermal delivery of this TCM and its anti-asthma effect were evaluated. Active components of white mustard seed, rhizoma corydalis and Radix Kansui were obtained after alcohol extraction, respectively. The volatile oil in Asarum Heterotropoides were obtained with volatile oil extraction equipment. The drug loading ratio of cataplasms was 17% (w/w). Franz cell diffusion method was used to evaluate the accumulated permeation amount and the steady-state transdermal absorption rate of sodium thiocyanate. The improvement of sonophoresis on transdermal absorption was higher than that of iontophoresis.Asthma model of guinea pigs were established. Cataplasms of white mustard seed varnish were applied on the back of guinea pigs. Iontophoresis and sonophoresis obviously promoted the transdermal absorption and enhanced anti-asthma efficacy of white mustard seed varnish cataplasms. Pathological analysis showed that iontophoresis and sonophoresis significantly alleviated inflammation. Compared with the model group, IL-4 and IgE levels in the cataplasm group, cataplasm/iontophoresis group, cataplasm/sonophoresis group decreased obviously, although the IFN-γ levels markedly increased. Moreover, the therapeutic efficacy of cataplasm/sonophoresis group was the best in all the groups, even leading to levels similar to that of healthy animals. Iontophoresis and sonophoresis are effective methods to promote transdermal absorption of cataplasms. Moreover, the effect of sonophoresis is higher than that of iontophoresis. Physical penetration improvement techniques provide a novel insight for the wide application of transdermal TCM.