Synthesis, characterization, and efficacy evaluation of a PH-responsive Fe-MOF@GO composite drug delivery system for the treating colorectal cancer.

Luteolin is a potent anti-colorectal cancer chemical. However, its effectiveness is hindered by its poor solubility in water and fat, and it is easy to degrade by gastrointestinal enzymes. In this study, a nano-composite carrier, NH2-MIL-101(Fe)@GO (MG), based on aminated MIL-101(Fe) and graphene oxide (GO) was developed and evaluated. This carrier co-delivered luteolin and matrine, while marine was used to balance the pH for the nano-preparation. The loading capacities for luteolin and matrine were approximately 9.8% and 14.1%, respectively. Luteolin's release at pH = 5 was significantly higher than at pH = 7.4, indicating it had an acidic pH response release characteristic. Compared to MOF and GO alone, MG and NH2-MIL-101(Fe)@GO@Drugs (MGD) enhanced anti-cancer activity by inhibiting tumor cell migration, increasing ROS generation, and upregulating the expression of Caspase-3 and Caspase-9. In conclusion, this study contributes new ideas and methods to the treatment strategy of multi-component anti-colorectal cancer therapy. It also advances drug delivery systems and supports the development of more effective and targeted treatment approaches for colorectal cancer.

[Permeation mechanism of phenolic acid components from traditional Chinese medicine on PES membrane separation process].

To explore the permeation mechanism of micro-molecule medicinal ingredients of water extract of tradition Chinese medicine(TCM) in membrane separation process. With phenolic acid components as the model solute, five phenolic acids with similar molecular weight and structure, namely gallic acid, protocatechuate acid, 4-hydroxybenzoic acid, 3-hydroxybenzoic acid and salicylic acid, were selected in the PES membrane separation experiments. With the relative flux and the transmission rate as indexes, the scanning electron microscopy(SEM) and the electrochemical impedance spectroscopy(EIS) were used to analyze the permeation mechanism of different phenolic acid components. The results showed phenolic acids with similar molecular weight had different permeation behaviors, with decreased relative flux and increased solute permeation with the increase of solute concentration. According to the permeation behavior analyzed by the molecular structure of solute, the transmission rate of phenolic acids increased with the increase of the number of hydroxyl, and the order of substituent positions of phenolic acids based on the permeation rate as follows: para-substituted > meta-substitution > ortho-substitution. Electrochemical impedance spectroscopy reflected the role of charge repulsion in the membrane process; that is to say, the greater the resistance is, the less the solute permeation is. Therefore, the permeation phenomenon of the phenolic acid components in the PES membrane is not only the result of simple sieving mechanisms, but also has the effects of steric hindrance and charge repulsion during the membrane process.

[Study on essential oil separation from Forsythia suspensa oil-bearing water body based on vapor permeation membrane separation technology].

To investigate the feasibility of vapor permeation membrane technology in separating essential oil from oil-water extract by taking the Forsythia suspensa as an example. The polydimethylsiloxane/polyvinylidene fluoride (PDMS/PVDF) composite flat membrane and a polyvinylidene fluoride (PVDF) flat membrane was collected as the membrane material respectively. Two kinds of membrane osmotic liquids were collected by self-made vapor permeation device. The yield of essential oil separated and enriched from two kinds of membrane materials was calculated, and the microscopic changes of membrane materials were analyzed and compared. Meanwhile, gas chromatography-mass spectrometry (GC-MS) was used to compare and analyze the differences in chemical compositions of essential oil between traditional steam distillation, PVDF membrane enriched method and PDMS/PVDF membrane enriched method. The results showed that the yield of essential oil enriched by PVDF membrane was significantly higher than that of PDMS/PVDF membrane, and the GC-MS spectrum showed that the content of main compositions was higher than that of PDMS/PVDF membrane; The GC-MS spectra showed that the components of essential oil enriched by PVDF membrane were basically the same as those obtained by traditional steam distillation. The above results showed that vapor permeation membrane separation technology shall be feasible for the separation of Forsythia essential oil-bearing water body, and PVDF membrane was more suitable for separation and enrichment of Forsythia essential oil than PDMS/PVDF membrane.

Explore the effects of Huang-Lian-Jie-Du-Tang on Alzheimer's disease by UPLC-QTOF/MS-based plasma metabolomics study.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with neither definitive pathogenesis nor effective treatment method so far. Huang-Lian-Jie-Du-Tang (HLJDT) is a classic formula of traditional Chinese medicine (TCM) proven to have ameliorative effects on learning and memory deficits of dementia. Morris water maze (MWM) test and pathology analysis have demonstrated that HLJDT could ameliorate learning and memory deficits in AD mouse model, which may act via its anti-neuroinflammation properties. According to our previous studies, an UPLC-QTOF/MS-based metabolomics approach was performed to explore the potential mechanisms of HLJDT on preventing AD. As a result, a total of 23 potential metabolites (VIP >1, |Pcorr| >0.58, CUFjk excludes 0, P < 0.05) contributing to AD progress were identified. The metabolic pathway analysis with MetPA revealed that glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism and tryptophan metabolism were disturbed in mouse model of AD. After HLJDT treatment, 14 metabolites were restored back to the control-like levels.

[Studies on preparation by SPG membrane emulsification method and in vitro characterization of tetradrine-tashionone II(A)-PLGA composite microspheres].

Tetradrine-tashionone II(A)-PLGA composite microspheres were prepared by the SPG membrane emulsification method, and the characterization of tetradrine-tashionone II(A) -PLGA composite microspheres were studied in this experiment. The results of IR, DSC and XRD showed that teradrine and tashionone II(A) in composite microspheres were highly dispersed in the PLGA with amorphous form. The results of tetradrine-tashionone II(A) -PLGA composite microspheres in vitro release experiment showed that the cumulative release amounts of tetradrine and tashionone II(A) were 6.44% and 3.60% in 24 h, and the cumulative release amounts of tetradrine and tashionone II(A) were 89.02% and 21.24% in 17 d. The process of drug in vitro release accorded with the model of Riger-Peppas. Tetradrine-tashionone II(A) -PLGA composite microspheres had slow-release effect, and it could significantly reduce the burst release, prolong the therapeutic time, decrease the dosage of drugs and provide a new idea and method to prepare traditional Chinese medicine compound.

[Preparation and release behaviour of mPEG-PLA α-asarone nanoparticles designed for nasal administration].

Taking α-asarone as model drug, mono methoxy polyethylene glycol-polylactic acid copolymer (mPEG-PLA) as the drug carrier material to prepare drug-loading nanoparticles by premix membrane emulsification for nasal administration. The prepared nanoparticles were spherical with smooth surface and average particle size of 360 nm. Polydispersity index (PDI) was 0. 030, average drug loading of (11.5 ± 0.045) % (n = 3), and the encapsulation efficiency of (86.34 ± 0.11) % (n = 3). X-ray diffraction and differential scanning calorimetry results showed that, α-asarone existed in mPEG-PLA carrier in amorphous or molecular state, different from simple physical mixture. In the in vitro release test in simulated human nasal cavity, α-asarone apis can be released quickly at close to 94% at 102 h, in line with the first-order kinetics (R² = 0.981 9). mPEG-PLA drug-loading nanoparticles release only 54%, with slow release effect, in line with Riger-Peppas model (R² = 0.967 9, n = 0.630 2), for non-fick diffusion, released by the spread of drugs and skeleton dissolution dual control. This provided the foundation for nasal drug delivery in vivo pharmacokinetic study.

[Optimization theory and practical application of membrane science technology based on resource of traditional Chinese medicine residue].

Resource of traditional Chinese medicine residue is an inevitable choice to form new industries characterized of modem, environmental protection and intensive in the Chinese medicine industry. Based on the analysis of source and the main chemical composition of the herb residue, and for the advantages of membrane science and technology used in the pharmaceutical industry, especially membrane separation technology used in improvement technical reserves of traditional extraction and separation process in the pharmaceutical industry, it is proposed that membrane science and technology is one of the most important choices in technological design of traditional Chinese medicine resource industrialization. Traditional Chinese medicine residue is a very complex material system in composition and character, and scientific and effective "separation" process is the key areas of technology to re-use it. Integrated process can improve the productivity of the target product, enhance the purity of the product in the separation process, and solve many tasks which conventional separation is difficult to achieve. As integrated separation technology has the advantages of simplified process and reduced consumption, which are in line with the trend of the modern pharmaceutical industry, the membrane separation technology can provide a broad platform for integrated process, and membrane separation technology with its integrated technology have broad application prospects in achieving resource and industrialization process of traditional Chinese medicine residue. We discuss the principles, methods and applications practice of effective component resources in herb residue using membrane separation and integrated technology, describe the extraction, separation, concentration and purification application of membrane technology in traditional Chinese medicine residue, and systematically discourse suitability and feasibility of membrane technology in the process of traditional Chinese medicine resource industrialization in this paper.

[Preparation and characterization of tetrandrine-loaded PLGA nanocomposite particles by premix membrane emulsification coupled with spray-drying method].

For effective inhalable dry-powder drug delivery, tetrandrine-PLGA (polylactic-co-glycolic acid) nanocomposite particles have been developed to overcome the disadvantages of nanoparticles and microparticles. The primary nanoparticles were prepared by using premix membrane emulsification method. To prepare second particles, they were spray dried. The final particles were characterized by scanning electron microscopy (SEM), dry laser particle size analysis, high performance liquid chromatography (HPLC), X-ray diffraction (XRD), differential scanning calorimetry (DSC), infrared analysis (IR) and confocal laser scanning microscope (CLSM). The average size of the primary particles was (337.5 ± 6.2) nm, while that second particles was (3.675 ± 0.16) µm which can be decomposed into primary nanoparticles in water. And the second particles were solid sphere-like with the drug dispersed as armorphous form in them. It is a reference for components delivery to lung in a new form.

[In vitro and in vivo study of fluorescent probe PLGA particles prepared by premix membrane emulsification method].

Relatively uniform-sized nanoparticles made of poly (lactic-co-glycolic acid) (PLGA) were prepared by premix membrane emulsification method. After the drug loading property was completed, the dynamic tissue distribution of nanoparticles was recorded. With the average particle size and span as indexes, membrane pore size, number of passing membrane times, membrane pressure, volume ratio of oil-water phase and the concentration of poly(vinyl alcohol) (PVA) in external water phase were investigated by single factor test, the optimum preparation technology of blank PLGA nanlparticles was as following: pore size of SPG membrane was 1 µm, membrane pressure was 1. 15 MPa, the number of passing membrane time was 3, the mass fraction of PVA of 2%, volume ratio of oil-water phase of 1 : 5. Prepared nanoparticles were round with smooth surface, the mean diameter was 332.6 nm, span was 0.010, the confocal laser scanning microscope (CLSM) concluded that fluorescent substance is uniform composizion in PLGA nanoparticle, and the in vivo imaging technology in mice include that the nanoparticles show good liver and spleen targeting property.

[Study on PK/PD model for traditional Chinese medicine biopharmaceutics based on principle of "correspondence of prescriptions and syndromes"].

In the principle of "correspondence of prescription and syndrome", this article focuses on key technical issues of traditional Chinese medicine (TCM) biopharmaceutis by using the integrated pharmacokinetic and pharmacodynamic model: (1) As the prescription formulation and compatibility of TCM compounds could be influential to the in vivo pharmacokinetics of chemical components of TCMs, and closely related to therapeutic and adverse effects, how to describe these actions in a biopharmaceutics model? (2) As there are differences between pharmacokinetic processes in the normal and pathological states, how to express characteristic "syndromes" in an animal model? (3) As prescriptions work to reduce and transform syndromes, how o confirm the type and amount of effective substances in case of physiological and pathological indicators and drug distribution in a dynamic corresponding state. In response to the above key issues, we proposed the TCM biopharmaceutic study model based on PK/PD. (1) The integrity of TCMs was better expressed with the effect at the core, supplemented with the component pharmacokinetics; (2) An integrated pharmacokinetic and pharmacodynamic system was established on the basis of pharmacokinetics and pharmacodynamics of many major effective components; (3) AK/PD mathematical function with the three-phase synchronous characterization of "time-concentration-effect" was established by using the data mining techniques, to explore the biopharmaceutic principle of "correspondence of prescriptions and syndromes", in which prescriptions are only required for syndromes, whereas no prescription is required in case of no syndrome.

Parameters optimization of supercritical fluid-CO2 extracts of frankincense using response surface methodology and its pharmacodynamics effects.

The volatile oil parts of frankincense (Boswellia carterii Birdw.) were extracted with supercritical carbon dioxide under constant pressure (15, 20, or 25 MPa) and fixed temperature (40, 50, or 60°C), given time (60, 90, or 120 min) aiming at the acquisition of enriched fractions containing octyl acetate, compounds of pharmaceutical interest. A mathematical model was created by Box-Behnken design, a popular template for response surface methodology, for the extraction process. The response value was characterized by synthetical score, which comprised yields accounting for 20% and content of octyl acetate for 80%. The content of octyl acetate was determined by GC. The supercritical fluid extraction showed higher selectivity than conventional steam distillation. Supercritical fluid-CO(2) for extracting frankincense under optimum condition was of great validity, which was also successfully verified by the pharmacological experiments.

Comparative pharmacokinetics of baicalin in plasma after oral administration of Huang-Lian-Jie-Du-Tang or pure baicalin in MCAO and sham-operated rats.

A sensitive and specific HPLC method was developed to analyze baicalin in rat plasma. The author had compared the pharmacokinetics of baicalin after oral administration of HLJDT decoction or pure baicalin in MCAO and sham-operated rats. All the rats were divided into two groups, MCAO and sham-operated rats. Each group contained two subgroups: HLJDT decoction and pure baicalin subgroup. The HLJDT subgroup oral administration of HLJDT decoction extract 10.00 g/kg according to body weight (containing baicalin 400.00 mg/kg according to body weight), the pure baicalin subgroup received a gavages at a dosage of baicalin 400.00 mg/kg according to body weight too. The pharmacokinetics parameters were analyzed by kinetica. The results indicated that the pharmacokinetics of baicalin in rat plasma was non-linear and there were significant differences between different groups. No matter in MCAO or sham-operated rats, pure baicalin had shown better absorption than HLJDT decoction. Whether administration of pure baicalin or HLJDT decoction, the MCAO rats show better, quicker absorption of baicalin than sham-operated rats. It was good for baicalin to exert pharmacological effects on healed cerebrovascular diseases. The method had been applied successfully to pharmacokinetics of baicalin in rat plasma after oral administration of pure baicalin or HLJDT decoction.

[Studies on bioactive constituents of whole herbs of Vernonia cinerea].

OBJECTIVE: To study the constituents of the whole herbs of Vernonia cinerea. by bio-activity guided isolation with PC-12 model. METHOD: The constituents were separated by column chromatography and the structures were elucidated by spectroscopic methods. RESULT: Four compounds were identified to be (+)-lirioresinol B (1), stigmasterol (2), stigmasterol-3-O-beta-D-glucoside (3), 4-sulfo-benzocyclobutene (4), and their NGF inducing activity were also investigated. CONCLUSION: Compounds 1, 3, 4 were isolated from this genus for the first time, and compound 4 was identified as a new natural product. Compounds 1, 3, 4 showed cytotoxicity on PC-12, and compounds 2, 3, 4 showed inhibition activity. Compound 4 showed a specific effect on the survival of TrkA fibroblasts, and resulted in the inducing NGF activity.