Preparation and characterization of solid lipid nanoparticles loaded with frankincense and myrrh oil

The aim of the present study was to prepare solid lipid nanoparticles (SLNs) for the oral delivery of frankincense and myrrh essential oils (FMO). Aqueous dispersions of SLNs were successfully prepared by a high-pressure homogenization method using Compritol 888 ATO as the solid lipid and soybean lecithin and Tween 80 as the surfactants. The properties of the SLNs such as particle size, zeta potential (ZP), and drug encapsulation efficiency (EE) were investigated. The morphology of SLNs was observed by transmission electron microscopy (TEM). The crystallinity of the formulation was analyzed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). In addition, drug evaporation release and antitumor activity were also studied. Round SLNs with a mean size of 113.3 ± 3.6 nm, a ZP of −16.8 ± 0.4 mV, and an EE of 80.60% ± 1.11% were obtained. DSC and XRD measurements revealed that less ordered structures were formed in the inner cores of the SLN particles. Evaporation loss of the active components in FMO could be reduced in the SLNs. Furthermore, the SLN formulation increased the antitumor efficacy of FMO in H22-bearing Kunming mice. Hence, the presented SLNs can be used as drug carriers for hydrophobic oil drugs extracted from traditional Chinese medicines

Performance of Arrhenotokous and Thelytokous Thrips tabaci (Thysanoptera: Thripidae) on Onion and Cabbage and Its Implications on Evolution and Pest Management

Onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae), is an important pest on onion and cabbage. Two reproductive modes—arrhenotoky and thelytoky—are found in this species and co-occur in the field. We compared life table traits between arrhenotokous and thelytokous T. tabaci on cabbage and onion. Experiments were conducted in cages to determine which reproductive mode is more competitive. Additionally, host adaption of the arrhenotokous and thelytokous T. tabaci between onion and cabbage was investigated. On onion, arrhenotokous T. tabaci performed better than thelytokous T. tabaci, while on cabbage the opposite occurred. When comparing life table and demographic growth parameters (net reproductive rates R0, mean generation time T, the intrinsic rate of natural increase rm, finite rate of increase λ, and population doubling time Td) on different host plants, we found that arrhenotokous T. tabaci performed better on onion than on cabbage, whereas thelytokous T. tabaci performed better on cabbage than on onion. Host-related performance differences in this species suggest that the divergence between two reproductive modes might be associated with host adaption. Pest management strategies for this global pest should recognize that the two reproductive modes can impact population dynamics on different crop

Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system

Zhi-Qiang Chen, Ying Liu, Ji-Hui Zhao, Lan Wang, Nian-Ping FengSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of ChinaBackground: Indirubin, isolated from the leaves of the Chinese herb Isatis tinctoria L, is a protein kinase inhibitor and promising antitumor agent. However, the poor water solubility of indirubin has limited its application. In this study, a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed to improve the oral bioavailability of indirubin.Methods: A prototype S-SMEDDS was designed using solubility studies and phase diagram construction. Precipitation inhibitors were selected from hydrophilic polymers according to their crystallization-inhibiting capacity through in vitro precipitation tests. In vitro release of indirubin from S-SMEDDS was examined to investigate its likely release behavior in vivo. The in vivo bioavailability of indirubin from S-SMEDDS and from SMEDDS was compared in rats.Results: The prototype formulation of S-SMEDDS comprised Maisine™ 35-1:Cremophor® EL:Transcutol® P (15:40:45, w/w/w). Polyvinylpyrrolidone K17, a hydrophilic polymer, was used as a precipitation inhibitor based on its better crystallization-inhibiting capacity compared with polyethylene glycol 4000 and hydroxypropyl methylcellulose. In vitro release analysis showed more rapid drug release from S-SMEDDS than from SMEDDS. In vivo bioavailability analysis in rats indicated that improved oral absorption was achieved and that the relative bioavailability of S-SMEDDS was 129.5% compared with SMEDDS.Conclusion: The novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of indirubin in rats. The results suggest that S-SMEDDS is a superior means of oral delivery of indirubin.Keywords: supersaturatable self-microemulsifying drug delivery system, indirubin, bioavailability, oral drug delivery, hydrophilic polyme

Enhanced transdermal delivery of evodiamine and rutaecarpine using microemulsion

Yong-Tai Zhang, Ji-Hui Zhao, Su-Juan Zhang, Yang-Zi Zhong, Zhi Wang, Ying Liu, Feng Shi, Nian-Ping FengSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaObjective: The purpose of this study was to improve skin permeation of evodiamine and rutaecarpine for transdermal delivery with microemulsion as vehicle and investigate real-time cutaneous absorption of the drugs via in vivo microdialysis.Methods: Pseudoternary phase diagrams were constructed to evaluate microemulsion regions with various surfactants and cosurfactants. Nine formulations of oil in water microemulsions were selected as vehicles for assessing skin permeation of evodiamine and rutaecarpine in ex vivo transdermal experiments. With a microdialysis hollow fiber membrane implanted in the skin beneath the site of topical drug administration, dialysis sampling was maintained for 10 hours and the samples were detected directly by high performance liquid chromatography. Real-time concentrations of the drugs in rat skin were investigated and compared with those of conventional formulations, such as ointment and tincture. Furthermore, the drugs were applied to various regions of the skin using microemulsion as vehicle.Results: In ex vivo transdermal experiments, cutaneous fluxes of evodiamine and rutaecarpine microemulsions were 2.55-fold to 11.36-fold and 1.17-fold to 6.33-fold higher, respectively, than those of aqueous suspensions. Different drug loadings, microemulsion water content, and transdermal enhancers markedly influenced the permeation of evodiamine and rutaecarpine. In microemulsion application with in vivo microdialysis, the maximum concentration of the drugs (evodiamine: 18.23 ± 1.54 ng/mL; rutaecarpine: 16.04 ± 0.69 ng/mL) were the highest, and the area under the curve0–t of evodiamine and rutaecarpine was 1.52-fold and 2.27-fold higher than ointment and 3.06-fold and 4.23-fold higher than tincture, respectively. A greater amount of drugs penetrated through and was absorbed by rat abdominal skin than shoulder and chest, and a reservoir in the skin was found to supply drugs even after the microemulsion was withdrawn.Conclusion: Compared to conventional formulations, higher cutaneous fluxes of evodiamine and rutaecarpine were achieved with microemulsion. Based on this novel transdermal delivery, the transdermal route was effective for the administration of the two active alkaloids.Keywords: microemulsion, evodiamine, rutaecarpine, transdermal delivery, microdialysi

In vitro cellular uptake of evodiamine and rutaecarpine using a microemulsion

Yong-Tai Zhang, Zhe-Bin Huang, Su-Juan Zhang, Ji-Hui Zhao, Zhi Wang, Ying Liu, Nian-Ping FengDepartment of Pharmaceutics, Shanghai University of Traditional Chinese Medicine, Shanghai, The People's Republic of ChinaObjective: To investigate the cellular uptake of evodiamine and rutaecarpine in a microemulsion in comparison with aqueous suspensions and tinctures.Materials and methods: A microemulsion was prepared using the dropwise addition method. Mouse skin fibroblasts were cultured in vitro to investigate the optimal conditions for evodiamine and rutaecarpine uptake with different drug concentrations and administration times. Under optimal conditions, the cellular uptake of microemulsified drugs was assayed and compared to tinctures and aqueous suspensions. Rhodamine B labeling and laser scanning confocal microscopy (LSCM) were used to explore the distribution of fluorochrome transferred with the microemulsion in fibroblasts. Cellular morphology was also investigated, using optical microscopy to evaluate microemulsion-induced cellular toxicity.Results: The maximum cellular drug uptake amounts were obtained with a 20% concentration (v/v) of microemulsion and an 8 hour administration time. Drug uptake by mouse skin fibroblasts was lowest when the drugs were loaded in microemulsion. After incubation with rhodamine B-labeled microemulsion for 8 hours, the highest fluorescence intensity was achieved, and the fluorochrome was primarily distributed in the cytochylema. No obvious cellular morphologic changes were observed with the administration of either the microemulsion or the aqueous suspension; for the tincture group, however, massive cellular necrocytosis was observed.Conclusion: The lower cellular uptake with microemulsion may be due to the fact that most of the drug loaded in the microemulsion vehicle was transported via the intercellular space, while a small quantity of free drug (released from the vehicle) was ingested through transmembrane transport. Mouse skin fibroblasts rarely endocytosed evodiamine and rutaecarpine with a microemulsion as the vehicle. The microemulsion had no obvious effect on cellular morphology, suggesting there is little or no cellular toxicity associated with the administration of microemulsion on mouse skin fibroblasts.Keywords: mouse skin fibroblasts, evodiamine, rutaecarpine, microemulsion, cellular uptake, in vitr

Dynamically generated 0^+ heavy mesons in a heavy chiral unitary approach

In terms of the heavy chiral Lagrangian and the unitarized coupled-channel scattering amplitude, interaction between the heavy meson and the light pseudoscalar meson is studied. By looking for the pole of scattering matrix on an appropriate Riemann sheet, a $DK$ bound state $D_{s0}^*$ with the mass of $2.312\pm0.041$ GeV is found. This state can be associated as the narrow $D_{sJ}^*(2317)$ state found recently. In the same way, a $B{\bar K}$ bound state $B_{s0}^*$ is found, and its mass of $5.725\pm0.039$ GeV is predicted. The spectra of $D_0^*$ and $B_0^*$ with $I=1/2$ are further investigated. One broad and one narrow states are predicted in both charm and bottom sectors. The coupling constants and decay widths of the predicted states are also calculated.Comment: 15 pages, 1 figure. One numerical error in Eq.16 correcte

On the structure of the pi pi invariant mass spectra of the Upsilon(4S)-->Upsilon(1S,2S) pi^+ pi^- decays

We perform a model-independent analysis for recently reported data of the $\pi^+\pi^-$ invariant mass spectra in the $\Upsilon(4S)\to\Upsilon(1S,2S)\pi^+\pi^-$ decays and point out that there does exist a broad peak below 0.6 GeV in the data of the $\Upsilon(4S)\to\Upsilon(1S)\pi^+\pi^-$ decay, which is analogous to that in the $\Upsilon(3S)\to\Upsilon(1S)\pi^+\pi^-$ decay. With the data of $\Upsilon(4S)$ decays, we further test our model developed for studying the puzzle in the $\Upsilon(3S)\to\Upsilon(1S)\pi^+\pi^-$ decay. The result shows that with such a model, all the $\pi^+\pi^-$ invariant mass spectra of $\Upsilon(4S)$ decays can be described. We also predict the $\cos\theta_{\pi}^*$ distributions of $\Upsilon(4S)\to\Upsilon(1S,2S)\pi^+\pi^-$ decays, which can be used to justify our model prediction.Comment: 11 pages, 5 figures. Extended to include new data; title changed. Version accepted for publication in Phys. Lett.