Structure-activity relationship of coptis alkaloid bitterness inhibited by mPEG-PLLA / 中国中药杂志

Inhibition of bitterness is a significant measure to improve the compliance and clinical efficacy of traditional Chinese medicine(TCM) decoction. According to the characteristics of TCM decoction, such as high dispersion of bitterness components, multi-component bitterness superposition and strong instantaneous stimulation, the research group put forward a new strategy to inhibit bitterness in the early stage based on the self-assembly characteristics of amphiphilic substances in aqueous solution, in order to reduce the distribution of bitterness components in real solution and achieve the purpose of bitter-masking. It was found that the bitter-masking effect of amphiphilic substances was different on the bitter compounds of various structures. Therefore, it was speculated that there might be a certain relationship between the bitter inhibition effect and the substrate structure. In this paper, the interaction between mPEG-PLLA and five bitter alkaloids(bamatine, jatrorrhizine, berberine, epiberberine and coptisine) in Coptidis Rhizoma was studied to explore the effect of substrate structure on the inhibition of bitterness. The sensory test of volunteers was used to determine the bitter-masking effect of mPEG-PLLA on the decoction of Coptidis Rhizoma and its main bitter alkaloids. The molecular docking and molecular force field were applied to locate the bitter groups and the bitter-masking parts. The relationship between the bitter strength and the structure was analyzed by the surface electrostatic potential of the bitter alkaloids, and the correlation between the bitter-masking effect and the structural parameters of the bitter components was explored by factor analysis, so as to clarify the structure-activity relationship of mPEG-PLLA in masking the bitterness of coptis alkaloids. It was found that mPEG-PLLA had significant taste masking effect on the decoction of Coptidis Rhizoma and five alkaloids. The masking effect was obviously related to the structure of different alkaloids: the effect increased with the increase of the number of hydrogen donors, rotatable bonds, molecular weight, and hydrophobicity, and decreased with the increase of surface electrostatic potential, electrophilicity and binding energy with bitter receptors. In this study, the influence of alkaloid structure of Coptidis Rhizoma on the butter-masking effect of mPEG-PLLA was preliminarily elucidated, providing a scientific basis for better exerting the bitter-masking effect of amphiphilic block copolymers.

In vivo and in vitro MR imaging of glioma targeted block copolymer micelles / 中华放射学杂志

Objective To explore the in vivo/in vitro MR imaging effect of Angiopep2 modified glioma targeted block copolymer micelles(ANPs/CPT). Methods Angiopep2 modified DOTA-Gd conjugated polymeric micelles based on beta-cyclodextrin(β-CD) were successfully synthesized.Water proton longitudinal relaxation rate (1/T1) were calculated to compare the r1of DOTA-Gd and ANPs/CPT. Different concentration of DOTA-Gd, NP/CPT, ANP/CPT were co-cultured with C6 cells, the intracellular content of Gd3+was analyzed by ICP-AES;The signal intensity(SI) and contrast to noise ratio(CNR) were measured by 1.5 T MR;The CNR of ANPs/CPT was evaluated on different organs of normal rats. The enhancement feature of ANP/CPT in glioma as well as T/N and CNR between tumor and normal brain tissue were also investigated.Several comparisons were made between the 3 groups by one-way ANOVA,and the difference were significant when P<0.05.Results The r1of ANPs/CPT(13.900 s-1·mmol/L-1)was 3 times as much as DOTA-Gd(4.927 s-1·mmol/L-1).C6 cells uptake different concentrations of Gd3 +had significant difference among groups(F=362.502,1636.136,386.880,918.173, P<0.001).The difference of SI and CNR among groups were significant(F=55.240,155.419,P<0.001).The CNR of the brain tissue had significant difference with other organs at all times after tail vein injection of ANPs/CPT(F=9.417,21.808, 21.383,107.318,178.762,P<0.01).The ANPs/CPT showed excellent brain-targeting efficiency and theT/N ratio(30 min after),CNR in different time point had significant difference among groups (F=5.349,6.594,24.078,18.508 and 6.840,6.780,5.895,12.620,37.139,368.893, P<0.05).Conclusions ANPs/CPT shows nice agnetic relaxation performance,extended blood circulation duration,excellent brain-targeting efficieney, which will render the theranosticnano-carriers with important reference for the construction of new generation multifunctional nanomedicine.

Block copolymer micelles as delivery system for poorly soluble antineoplastic carrier / 中草药

To review the research of block copolymer micelles as delivery system for poorly soluble(antineoplastic) carrier over the last 10 years,including the composition,preparation methods and factors which influence the loading efficiency,physicochemical properties,and targeting characteristics of block copolymer micelles.Block copolymer micelles are self-assembled structures formed from amphiphilic block copolymers by dispersing in aqueous media.The hydrophilic blocks of the copolymer form the outer shell of the micelle,while the hydrophobic blocks form the inner core,and the proper coreshell micellar architecture was constituted.Block copolymer micelles have a whole set of unique properties,such as small sizes,narrow particle size distribution,high drug loading capacities,and available disposition characteristics in the body.Block copolymer micelles have been found as promising drug carriers due to making poorly soluble antineoplastic lysis,toxicities and side effects decrease,bioavailability increase,and targeting the drugs to specific sites in a passive way or attaching ligands in an active way,which can be specifically(recognized) by receptors onto the surface of copolymers.