A narrative review on the development of the ethical review mode of multicenter clinical trials in China.

Background and Objective: The number of new drug clinical trials in China is surging, and ethics review played an important part in clinical trials. However, there are certain problems of ethical review in China. This review aims to conduct a review to propose recommendations of an ethical review mode for multicenter clinical trials and ultimately contribute to improving the ethics review mechanism and the efficiency. Methods: A literature review, publication research and interpretation of the related governmental policies and requirements in China were conducted to collect available information for analysis of the current situation in terms of the various ethical review modes for multicenter clinical research. The literatures and information were searched and selected from national and international database and related governance website by following some inclusion and exclusion criteria. And a comparation with the relevant practical experience in the USA was conducted to support the proposing of recommendations to China by referring to some successful practice in the USA. Key Content and Findings: China has undergone several stages of development. The most traditional and least efficient model is institutional review boards (IRBs) review, which is most commonly used. After IRB review mode, other modes such as central IRB and single IRB review have emerged, which have improved the efficiency of ethical review. However, multiple challenges exist like, no clear definition of regulatory responsibilities and the consensus is not easy to be made due to the gap of interpretation and the unbalanced development on ethic review system from Chinese hospitals. Conclusions: The multicenter ethical review should adopt the conditional 'approval' mode of the leading site's ethical review decisions, gradually establish a single IRB review and select the best ethics committee. Regional ethics committees can gradually take responsibility for the primary review in the multicenter ethics review model and ultimately contribute to improving the mechanism and efficiency of the ethics review.

Lectin-conjugated PLGA nanoparticles loaded with thymopentin: ex vivo bioadhesion and in vivo biodistribution.

The conjugation of lectins onto PLGA nanoparticles has been demonstrated to effectively improve the intestinal absorption of thymopentin. In this study, thymopentin-loaded nanoparticles made from fluorescein isothiocyanate labeled PLGA were modified with wheat germ agglutinin (WGA). The specific bioadhesion of nanoparticles on rat intestinal mucosa was studied ex vivo. An important increase of interaction between WGA-conjugated nanoparticles and the intestinal segments was observed compared with that of the unconjugated one (p<0.05). Fluorescence photomicrographs confirmed the bioadhesion of WGA-conjugated nanoparticles on intestinal villous epithelium as well as Peyer's patches. Biodistribution of nanoparticles was evaluated using tissues obtained from rats, to which nanoparticles were orally administered. The highest amount of WGA-conjugated nanoparticles was detected in small intestine, suggesting an increase of intestinal bioadhesion and endocytosis. The systemic uptake was as high as 6.48-13.4% of dose at 1 day and 7.32-15.26% at 7 days, which representing an increase of almost 1.4-3.1 fold across the intestine compared to <4.9% of the unconjugated one. The enhanced uptake was related to the increasing of WGA density on nanoparticles. These results further revealed the promising potential of lectin-conjugated nanoparticles on the improvement of intestinal bioadhesion and absorption for oral drug delivery.

[Preparation of lectin-conjugated PLGA nanoparticles and evaluation of their in vitro bioadhesive activity].

In this study, wheat germ agglutinin (WGA), tomato lectin (TL) and asparagus pea lectin (AL) were covalently coupled to conventional poly lactic-co-glycolic acid (PLGA) nanoparticles using a carbodiimide method to take the bioadhesive properties. The influences of the amounts of activating agents and lectins, as well as the activating time and incubating time on the effect of lectin conjugating were investigated to optimize the preparation conditions. The mean diameters of the performed nanoparticles with or without lectin conjugation ranged from (140.7 +/- 5.7) nm to (245.6 +/- 18.3) nm. The yields of lectin conjugating and the lectin surface concentrations on nanoparticles were determined by Lowry's methods, and were calculated to be (18.97 +/- 2.9)% - (20.15 +/- 2.4)% and (9.46 +/- 1.45)--(10.05 +/- 1.19) microg x mg(-1), respectively. The in vitro bioadhesive activities of nanoparticles were evaluated by pig gastric mucin (PM) binding experiments. After incubation at room temperature for 60 min, the equilibria of binding between nanoparticles and PM reached. The percentages of the bulk PM which had interacted with different lectin-conjugated PLGA nanoparticles were 15.5%, 12.1% and 11.8%, respectively. The conjugation of lectin enhanced the interaction about 2.4 - 3.2 fold compared with that of the non-conjugated one. A mathematical model was used based on the Langmuir equation, and the rate constants of interaction (k) were calculated to be 2.373 x 10(-3), 1.536 x 10(-3) and 1.714 x 10(-3) (microg x min/mL)(-1), respectively. These interactions could be competitively inhibited by their corresponding sugars of lectins. The results suggested that lectin-conjugated PLGA nanoparticles greatly promoted the interaction with PM in vitro compared with the conventional PLGA nanoparticles, thus would improve the bioadhesion on gastrointestinal mucosa after oral administration resulting in a prolonged residence time in the gastrointestinal tract.

Preparation and evaluation of lectin-conjugated PLGA nanoparticles for oral delivery of thymopentin.

The purpose of this study was to design and evaluate lectin-conjugated PLGA nanoparticles for oral delivery of thymopentin. Thymopentin loaded PLGA nanoparticles (TP5-NPs) were prepared by a double emulsion-solvent evaporation technique. Novel WGA-PLGA conjugates were synthesized by coupling the amino groups of wheat germ agglutinin (WGA) to the carbodiimide-activated carboxylic groups of PLGA, and were incorporated into nanoparticles preparation to take mucoadhesive properties. Important characteristics such as particle size, zeta potential, entrapment efficiency, storage stability, as well as in vitro drug release behavior were investigated. The retention of biorecognitive activity of WGA after covalent coupling was confirmed by haemagglutination test. In vitro experiments with pig mucin (PM) demonstrated that the conjugation of WGA enhanced the interaction about 1.8-4.2 fold compared with that of the non-conjugated nanoparticles, and still exhibited sugar specificity. The pharmacodynamical studies on oral administration of WGA-TP5-NPs were performed in FACScan flow cytometry. The values of CD4(+)/CD8(+) ratios were significantly increased compared with that of TP5-NPs (p<0.01). The enhanced uptake was related to the increasing of WGA content on nanoparticles. These results confirmed that the conjugation of WGA onto PLGA nanoparticles effectively improved the intestinal absorption of TP5 due to specific bioadhesion on GI cell membrane.

[Study on influence of buffer system on separate capacity of macroporous resin on ferulic liposome].

OBJECTIVE: To study the effect of buffer on separate capacity of macroporous resin. To evaluate the quality of ferulic acid liposome and determine its entrapment efficiency. METHOD: Different type of macroporous resin counterpoised by buffer system of Na2 HPO3-NaH2, PO3 was used to separate the free ferulic acid from the preparation and HPLC was used to determine the concentration of the ferulic acid to calculate the entrapment efficiency. RESULT: This method had good linearity in the range of 0.56 - 2.8 g x mL(-1) (r = 0.999 6). The precision RSD was less than 1.1%. The adsorption effect of macroporous resin on liposome was reduced while it had no effect on the absorption ability of macroporous resin on the ferulic acid by the usage of buffer. The recovery of HPD450 resin on blank liposome was between 97.2% - 100.8%, while the average recovery is 98.1%. CONCLUSION: Buffer system can enhance the separate ability of macroporous resin on liposome and free drug.