Preparation of mesoporous silica nanoparticles with different sizes and study on the correlation between size and toxicity / 药学学报

To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.

Preparation and evaluation of arsenic trioxide glioma targeting drug delivery system loaded by PAMAM dendrimers co-modified with RGDyC and PEG / 中国中药杂志

Arsenic trioxide (ATO) is an effective component of traditional Chinese medicine arsenic. The existing studies have shown its good inhibition and apoptosis ability on a variety of tumours. However, its toxicity and difficulties in the permeability into the blood brain barrier (BBB) has the limitation in the application of glioma treatment. Polyamide-amine dendrimer (PAMAM) is a synthetic polymer with many advantages, such as a good permeability, stability and biocompatibility. Additionally, the 5th generation of PAMAM is an ideal drug carrier due to its three-dimensional structure. In this study, the 5th generation of PAMAM co-modified with RGDyC and PEG, then confirmed by ¹H-NMR. The average particle size of nanoparticles was about 20 nm according to the nanoparticle size-potential analyser and transmission electron microscopy. release showed that the nanocarrier not only has the sustained release effect, but also some pH-sensitive properties. The cell results showed that PAMAM co-modified with RGDyC and PEGAM has a lower cytotoxicity than the non-modified group . Accordingly, the drug delivery system has a better anti-tumour effect across the blood brain barrier (BBB) , which further proves the tumour targeting of RGDyC.

Preparation technology of sinomenine hydrochloride liposomes / 中草药

Objective: To prepare sinomenine hydrochloride (SIN-HCl) liposomes with high entrapment efficiency (EE) and to illustrate the effects of drug quantity and particle size on EE. Methods: Centrifugation sedimentation-centrifugation ultrafiltration was employed to determine EE of liposomes. Thin film hydration (TFH), reverse phase evaporation (REV), and ether injection (EI) were screened based on EE and formability of liposomes. The effects of water type, pH value, ion concentration of hydration liquid, pH gradient active drug loading, lecithin-cholesterol ratio, and drug-lipid ratio on EE of liposomes were investigated. The relationship between EE and the factors affecting the drug quantity and particle size was probed with a comprehensive design experiment. The stability of typical liposomes was evaluated at 4 °C. Results: The optimal preparation technology was TFH for SIN-HCl liposomes and citrate buffer solution (CBS) was the best hydration liquid. The liposome EE increased with the increase of pH values of CBS. When the pH value of CBS was fixed, the EE increased as a result of decrease in the ion concentration of CBS. pH gradient active drug loading led to increase of EE. The preferable hydration liquid for liposomes was CBS with pH value of 2.5. The optimal ratio of soybean lecithin to cholesterol was 6:1. Increasing ratios of SIN-HCl to soybean lecithin from 1:6 to 6:6 led to a slight decrease in EE of liposomes without probe signification. A quantitative relationship was established between the EE and drug quantity and liposome size. The EE of SIN-HCl liposomes prepared by certain particle size and drug quantity could reach over 80%. The typical liposomes showed a good stability. Conclusion: The technology of pH gradient active drug loading is able to prepare SIN-HCl liposomes with high EE.

Determination of entrapment efficiency of sinomenine hydrochloride liposomes with centrifugation sedimentation combined with centrifugation ultrafiltration / 中草药

Objective: To develop a method for determining the entrapment efficiency of sinomenine hydrochloride (SM-HCl) liposomes and to illuminate the drug retention property in the liposomes. Methods: Thin film hydration method was employed to prepare SM-HCl liposomes. HPLC was used to determine drug content of the liposomes. A Kromasil ODS C18 column (250 mm x 4.6 mm, 5 μ) was used with an isocratic elution composed of methanol, water, and ethylenediamine in the ratio of 55 : 45 : 0.225 at a flow rate of 1.0 mL/min. The column was maintained at 30 °C. The UV detector was set at 265 nm. Centrifugation sedimentation combined with centrifugation ultrafiltration was used to determine drug entrapment efficiency of the liposomes. The entrapment efficiencies of an SM-HCl liposome sample (hydrated with citric buffer solution at pH 7.0) and its diluted sample were compared. Results: The pharmaceutical excipients and solvents for analysis had no interference with the determination of sinomenine. Sinomenine had a good linear relation in the range of 9.82-78.6 μg/mL (r = 0.999 7), the intra-day and inter-day precisions were with RSD≤2.1% and the averaged recovery was within 99.29%-100.8%. SM-HCl solution (50 μL) was able to saturate the drug absorption of ultrafiltration films. The entrapment efficiencies of the SM-HCl liposome sample (hydrated with citric buffer solution at pH 7.0) and its double-volume diluted sample were 33.16% and 14.75%, respectively. Conclusion: HPLC and centrifugation sedimentation combined with centrifugation ultrafiltration are able to determine the entrapment efficiency of SM-HCl liposomes efficiently and accurately. Initial filtrate (50 μL) should be discarded in the process of ultrafiltration in order that the drug concentration in filtrate may be equal to that of external aqueous phase of liposomes. The retention of sinominine in the liposomes is poor, although it has considerable affinity to the lipid bilayers.

Determination of vitexin-rhamnoside in Beagle dog plasma and preliminary pharmacokinetics of Yixintong sustained release tablets / 中国中药杂志

<p><b>OBJECTIVE</b>To develop an HPLC method to determine vitexin-rhamnoside in plasma of Beagle dogs and study the pharmacokinetics and bioavailability of Yixintong sustained release tablets in Beagle dogs.</p><p><b>METHOD</b>A newly-developed HPLC method using C18 column and methanol-acetonitrile-tetrahydrogenfuran-0.5% acetic acid (1:1:19.4:78.6) as mobile phase was validated, and then was employed to determine vitexin-rhamnoside in plasma of Beagle dogs after oral administration of Yixintong sustained release tablets and general tablets. The main pharmacokinetic parameters were estimated by pharmacokinetic program 3p87. The non-compartmental pharmacokinetic parameters were also calculated on basis of the statistic moment theory.</p><p><b>RESULT</b>The pharmacokinetic profiles of Yixintong sustained release tablets and the general tablets were fitted to a one-and two-compartment open model, respectively. The T1/2, Tmax, AUC0-infinity and MRT for Yixintong sustained release tablets were 5.22 h, 4.0 h, 6,792.75 ng x h x mL(-1) and 8.4 h, respectively, compared with 8.94 h, 1.0 h, 5,880.4 ng x h x mL(-1) and 6.1 h for the general tablets. The relative bioavailability of the Yixintong sustained release tablets was 115.5% in Beagle dogs.</p><p><b>CONCLUSION</b>The sustained-release characteristic of Yixintong sustained release tablets were confirmed by pharmacokinetic study.</p>

Research progress on oral prolonged-release preparation of traditional Chinese medicine / 中国中药杂志

This paper reviews the lastest progress on oral prolonged-release preparation of traditional Chinese medicine. Four materials, include component, effective parts, single drug, and compound drugs of traditiong Chinese medicine, have been used to produce oral prolonged-release preparation. The main contents are study of preparation and evaluation of in vitro release. There are also some research works on integrative evaluation, pharmacokinetics and pharmacological activity of the prolonged-release preparation. It believes that the study on oral prolonged-release preparation of traditional Chinese medicine will have good prospect.

Preparation of ondansetron hydrochloride osmotic pump tablets and their in vitro drug release / 药学学报

<p><b>AIM</b>To prepare ondansetron hydrochloride osmotic pump tablets (OND-OPT) and investigate their in vitro drug release behavior.</p><p><b>METHODS</b>OND-OPT were prepared with a single punch press and pan coating technique. Osmotic active agents and plasticizer of coating film were chosen by drug release tests. The effects of the number, position and direction of drug release orifice on release behavior were investigated. The relation between drug release duration and thickness of coating film, PEG content of coating film and size of drug release orifice was established by uniform design experiment. The surface morphological change of coating film before and after drug release test was observed by scanning electron microscopy. The osmotic pumping release mechanism of OND-OPT was confirmed by drug release test with high osmotic pressure medium.</p><p><b>RESULTS</b>Lactose-mannitol (1:2) was chosen as osmotic active agents and PEG400 as plasticizer of coating film. The direction of drug release orifice had great effect on the drug release of OND-OPT without HPMC, and had no effect on the drug release of OND-OPT with HPMC. The OND-OPT with one drug release orifice at the centre of the coating film on one surface of tablet released their drug with little fluctuation. The drug release duration of OND-OPT correlated with thickness of coating film and PEG content of coating film, and didn't correlate significantly with the size of drug release orifice. OND-OPT released their drug with osmotic pumping mechanism predominantly.</p><p><b>CONCLUSION</b>OND-OPT are able to realize ideal controlled drug release.</p>