Construction of the small intestine on molecular dynamics simulation and preliminary exploration of drug intestinal absorption prediction.

In this study, molecular dynamics simulation was applied to the construction of the small intestinal epithelial cell membrane and prediction of drug absorption. First, we constructed a system of a small intestinal epithelial cell membrane that was close to the real proportion and investigated the effects of temperature, water layer thickness, and ionic strength on membrane properties to optimize environmental parameters. Next, three drugs with different absorptivity, including Ephedrine (EPH), Quercetin (QUE), and Baicalin (BAI), were selected as model drugs to study the ability of drugs through the membrane by the free diffusion and umbrella sampling simulation, and the drug permeation ability was characterized by the free diffusion coefficient D and free energy barrier (△G) in the processes. The results showed that the free diffusion coefficient D and △G orders of the three drugs were consistent with the classical experimental absorption order, indicating that these two parameters could be used to jointly characterize the membrane permeability of the drugs.

Formulation design and mechanism study of hydrogel based on computational pharmaceutics theories.

Formulation design and mechanism study of the drug delivery system (DDS) is an important but difficult subject in pharmaceutical research. The study of formulation factors is the most time- and labor-consuming work of formulation design. In this paper, a multiscale computational pharmaceutics strategy was developed to guide the systematic study of formulation factors of a typical polymer-based DDS, hydrogel, and further to guide the formulation design. According to the strategy, the combination of solubility parameter (δ) and diffusion coefficient (D) calculated by the AA-MD simulation was suggested as the general evaluation method for the matrix screening of the hydrogels at the pre-formulation stage. At the formulation design stage, the CG-MD simulation method was suggested to predict the morphology and drug-releasing behavior of the hydrogels under different formulation factors. The influence mechanism can be explained by the combination of multiple parameters, such as the microstructure diagram, the radius of gyration (Rg), the radial distribution function (RDF), and the free diffusion volume (Vdiffusion). The simulation results are in good agreement with the in vitro release experiment, indicating that the strategy has good applicability.

Diammonium Glycyrrhizinate-Based Micelles for Improving the Hepatoprotective Effect of Baicalin: Characterization and Biopharmaceutical Study.

Saponins are an important class of surface-active substances. When formulated as an active ingredient or co-used with other drugs, the effect of their surface activity on efficacy or safety must be considered. In this paper, diammonium glycyrrhizinate (DG), a clinical hepatoprotective drug that has long been used as a biosurfactant, was taken as the research object to study its combined hepatoprotective effect with baicalin (BAI). Animal experiments proved that the preparation of DG and BAI integrated into micelles (BAI-DG Ms) had a better protective effect on acute liver injury caused by carbon tetrachloride than the direct combined use of the two. From the perspective of biopharmaceutics, the synergistic mechanism of BAI-DG Ms was further explored. The results showed that after forming BAI-DG Ms with DG, the solubility of BAI increased by 4.75 to 6.25 times, and the cumulative percentage release in the gastrointestinal tract also increased by 2.42 times. In addition, the negatively charged BAI-DG Ms were more likely to penetrate the mucus layer and be absorbed by endocytosis. These findings provide support for the rational application of glycyrrhizin, and other saponins.

Saponin surfactants used in drug delivery systems: A new application for natural medicine components.

Saponins are a group of compounds widely distributed in the plant kingdom. Due to their amphiphilic characteristic structure, saponins have high surface activity and self-assembly property and can be used as natural biosurfactants. Therefore, saponin has become a potential drug delivery system (DDS) carrier and has attracted the attention of many researchers. Increasing studies have found that when drugs combining with saponins, their solubility or bioavailability are improved. This phenomenon may be due to a synergistic mechanism and provides a potentially novel concept for DDS: saponins may be also used for carrier materials. This review emphasized the molecular characteristics and mechanism of saponins as carriers and the research on the morphology of saponin carriers. Besides, the article also introduced the role and application of saponins in DDS. Although there are still some limitations with the application of saponins such as cost, applicability, and hemolysis, the development of technology and in-depth molecular mechanism research will provide saponins with greater application prospects as DDS carriers.

Investigation on drug entrapment location in liposomes and transfersomes based on molecular dynamics simulation.

In this study, liposome and transfersome were successfully constructed using molecular dynamics simulation. Three drugs with different polarity, including 5-fluorouracil, ligustrazine, and osthole, were selected as model drugs to study the distribution of drugs in lipid vesicles by calculating the radial distribution function and the potential of mean force. The solubility parameters between drugs and different regions in lipid vesicles were calculated to characterize the compatibility of drugs in different regions in lipid vesicles, which provided the basis for the conclusion of this paper. It showed that the radial distribution function and the potential of mean force were consistent in the characterization of drug distribution in vesicles, and the drug distribution in vesicles was closely related to the compatibility between drugs and vesicles. Therefore, the radial distribution function and the potential of mean force can be used to characterize the distribution of drugs in vesicles, and molecular simulation technology has a great potential in studying the characteristics of vesicles. Graphical abstract.

The Application of Coarse-Grained Molecular Dynamics to the Evaluation of Liposome Physical Stability.

Physical stability is one of critical characteristics of liposome, especially to its clinical application. Vesicle fusion was one of the common physical stability phenomena that occurred during the long storage period. Because vesicle fusion could be easily checked by the change of vesicle size, it was widely applied in the evaluation of liposome physical stability. However, since the method requires the liposome to be placed under certain conditions for long-term observation, a liposome physical stability test usually takes several weeks, which greatly hinders the research efficiency. In this study, to speed up the research efficiency, coarse-grained molecular dynamics was first applied in the study of liposome physical stability. By analyzing the microprocess of vesicle fusion, two parameters including diffusion constant and the total time of the vesicle morphology transition process were employed to study the liposome physical stability. Then, in order to verify the applicability of two parameters, the physical stability of elastic liposomes and conventional liposomes was compared at 3 different temperatures. It was found that the fusion probability and speed of elastic liposomes were higher than those of conventional liposomes. Thus, elastic liposomes showed a worse physical stability compared with that of conventional liposomes, which was consistent with former research. Through this research, a new efficient method based on coarse-grained molecular dynamics was proposed for the study of liposome physical stability.