Characterization of the Composition and Biological Activity of the Venom from Vespa bicolor Fabricius, a Wasp from South China.

We analyzed, for the first time, the major components and biological properties of the venom of Vespa bicolor, a wasp from South China. Using HPLC and SDS-PAGE, combined with LC-MS/MS, MALDI-TOF-MS, and NMR data to analyze V. bicolor venom (VBV), we found that VBV contains three proteins (hyaluronidase A, phospholipase A1 (two isoforms), and antigen 5 protein) with allergenic activity, two unreported proteins (proteins 5 and 6), and two active substances with large quantities (mastoparan-like peptide 12a (Vb-MLP 12a), and 5-hydroxytryptamine (5-HT)). In addition, the antimicrobial activity of VBV was determined, and results showed that it had a significant effect against anaerobic bacteria. The minimum inhibitory concentration and minimum bactericidal concentration for Propionibacterium acnes were 12.5 µg/mL. Unsurprisingly, VBV had strong antioxidant activity because of the abundance of 5-HT. Contrary to other Vespa venom, VBV showed significant anti-inflammatory activity, even at low concentrations (1 µg/mL), and we found that Vb-MLP 12a showed pro-inflammatory activity by promoting the proliferation of RAW 264.7 cells. Cytotoxicity studies showed that VBV had similar antiproliferative effects against all tested tumor cell lines (HepG2, Hela, MCF-7, A549, and SASJ-1), with HepG2 being the most susceptible. Overall, this study on VBV has high clinical importance and promotes the development of Vespa bicolor resources.

Semi-solid extrusion 3D printing ODFs: an individual drug delivery system for small scale pharmacy.

Orodispersible films (ODFs) are promising drug delivery systems for customized medicines as it provide an alternative approach to increase consumer acceptance by advantages of rapid dissolution and administration without water. The aim of this study was to develop a platform to support the realization of tailored treatments suitable for the extemporaneous production of ODFs by semi-solid extrusion (SSE) 3D printing (3DP). Hydroxypropyl methyl cellulose (HPMC) was used as the polymer of ODFs, and levocetirizine hydrochloride was used as the model drug. The optimal formulation was HPMC:API:PS:maltitol:sucralose at a ratio of 64:10:10:15:1. Seventeen percent HPMC solution and optimal formulation were used to prepare film precursors. The impact of dynamic viscosities and fluid mechanics difference on printing applicability was discussed. The ODFs of cube designs with aimed dose of 1.25 mg, 2.5 mg, and 5 mg were printed by SSE 3DP. Good linear relationship between theoretical model volume and drug content (R2 = 0.999) and good dose accuracy indicate that 3DP is a suitable method for preparing individualized ODFs.

Applications of excipients in the field of 3D printed pharmaceuticals.

The aim of this study was to determine the effect of varying excipient content on the formation and physical properties of 3 D printed tablets. Fifteen different excipient preparations were formed into tablets with radii of 5 mm and thickness of 2 mm, using binder jetting (BJ). The tablets were analyzed by assessing visual and microstructural appearance, friability, hardness, and disintegration time. We found that filling agents with high water solubility (e.g. D-sucrose), binding agents with a high viscosity in solution (e.g. polyethylene glycol 4000) and moistening agent with higher water content can increase the bonding strength and hardness of the 3 D printed tablets and prolonged their disintegration time. This work has demonstrated that the type of excipient and its concentration affects the properties of the 3 D printed tablet. This article may be used as a guide for elucidation of the effects of using conventional tablet excipients in the field of 3 D printed pharmaceuticals. The present work should enable the identification of excipients that satisfy requirements, reduce analysis time, and improve efficiency.

Oral disintegrating patient-tailored tablets of warfarin sodium produced by 3D printing.

Individualized medicine is a new direction in the field of modern pharmacy. In this study, we assessed the feasibility and accuracy of 3D printing techniques for the preparation of individualized doses of mouth-disintegrating tablets of warfarin. Warfarin sodium, D-sucrose, pregelatinized starch, povidone K30, microcrystalline cellulose, and silicon dioxide (at a ratio of 1:42.45:46.15:5.1:4.9:0.4) were mixed and used as the printing powder in the 3D printer; preset parameters were used. The dosage of the tablet was controlled by the number of printing layers. The content, dose uniformity, dose accuracy, hardness, friability, disintegration time, dissolution, and the microstructural and overall appearance were determined to evaluate the printed tablets. For the doses of 3, 2, and 1 mg that were produced in the experiment, the disintegration times were 50.0 ± 5.2, 35.7 ± 4.3, and 11.0 ± 2.2 s, respectively, and the relative errors of the dose were -2.33, -1.50, and 0%, respectively. The other indicators were consistent with the preparation requirements of pharmaceutical tablets. It is possible to prepare tablets with excellent properties and controlled drug doses by using 3D printing techniques. This technology will be an important means to achieve individualized medicine.

Novel histone deacetylase inhibitor N25 exerts anti-tumor effects and induces autophagy in human glioma cells by inhibiting HDAC3.

N25, a novel histone deacetylase inhibitor, was created through structural modification of suberoylanilide hydroxamic acid. To evaluate the anti-tumor activity of N25 and clarify its molecular mechanism of inducing autophagy in glioma cells, we investigated its in vitro anti-proliferative effect and in vivo anticancer effect. Moreover, we detected whether N25 induces autophagy in glioma cells by transmission electron microscope and analyzed the protein expression level of HDAC3, Tip60, LC3 in glioma samples by western blot. We additionally analyzed the protein expression level of HDAC3, Tip60, ULK1 (Atg1), and Beclin-1 (Atg6) after treatment with N25 in glioma cells. Our results showed that the anti-tumor activity of N25 in glioma cells is slightly stronger than SAHA both in vitro and in vivo. We found that N25 induced autophagy, and HDAC3 was significantly elevated and Tip60 and LC3 significantly decreased in glioma samples compared with normal brain tissues. Nevertheless, N25 inhibited HDAC3 and up-regulated the protein expression of Tip60, ULK1 (Atg1), and Beclin-1 (Atg6) after treatment of glioma cells with N25. In conclusion, these data suggest that N25 has striking anti-tumor activity in part due to inhibition of HDAC3. Additionally, N25 may induce autophagy through inhibiting HDAC3.

[Study on formulation of naoxuekang dispersible tablets].

OBJECTIVE: To study the formulation of Naoxuekang dispersible tablets. METHODS: The formulation was determined by pre-processing leech extractum prior to a series of experiments used to screen excipients like bulking agents and disintegrants and so on, and by adding disintegrants within and without. RESULTS: Microcrystalline cellulose was determined as the bulking agent, and carboxymethyl cellulose and low-substituted hydroxypropyl cellulose were determined as the disintegrants of Naoxuekang dispersible tablet formula. The average disintegration time and nitrogen content of one tablet were 52 seconds and 5.47 milligrams, respectively. Also disperse homogeneity, weight variation and microbial limit all met the requirements in Ch. P. CONCLUSION: The prepared Naoxuekang dispersible tablet is reasonable in formula, feasible in technology, which meets the quality standards.