pH-Responsive Self-Assembled Nanoparticles for Tumor-Targeted Drug Delivery.

Recent advances in the field of drug delivery have opened new avenues for the development of novel nanodrug delivery systems (NDDS) in cancer therapy. Self-assembled nanoparticles (SANPs) based on tumor microenvironment have great advantages in improving antitumor effect, and pH-responsive SANPs prepared by the combination of pH-responsive nanomaterials and self-assembly technology can effectively improve the efficacy and reduce the systemic toxicity of antitumor drugs. In this review, we describe the characteristics of self-assembly and its driving force, the mechanism of pH-responsive NDDS, and the nanomaterials for pH-responsive SANPs type. A series of pH-responsive SANPs for tumor-targeted drug delivery are discussed, with an emphasis on the relation between structural features and theranostic performance.

UPLC-Q-Exactive Orbitrap-MS and network pharmacology for deciphering the active compounds and mechanisms of stir-fried Raphani Semen in treating functional dyspepsia.

BACKGROUND: As a traditional digestive medicine, stir-fried Raphani Semen (SRS) has been used to treat food retention for thousands of years in China. Modern research has shown that SRS has a good therapeutic effect on functional dyspepsia (FD). However, the active components and mechanism of SRS in the treatment of FD are still unclear. OBJECTIVE: The purpose of this study is to elucidate the material basis and mechanism of SRS for treating FD based on UPLC-Q-Exactive Orbitrap MS/MS combined with network pharmacology and molecular docking. METHODS: The compounds of SRS water decoction were identified by UPLC-Q-Exactive Orbitrap MS/MS and the potential targets of these compounds were predicted by Swiss Target Prediction. FD-associated targets were collected from disease databases. The overlapped targets of SRS and FD were imported into STRING to construct Protein-Protein Interaction (PPI) network. Then, the Metascape was used to analyze Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway after introducing overlapped targets. Finally, the active components and core targets were obtained by analyzing the "component-target-pathway" network, and the affinity between them was verified by molecular docking. RESULTS: 53 components were identified, and 405 targets and 1487 FD-related targets were collected. GO and KEGG analysis of 174 overlapped targets showed that SRS had important effects on hormone levels, serotonin synapses, calcium signaling pathway and cAMP signaling pathway. 7 active components and 15 core targets were screened after analyzing the composite network. Molecular docking results showed that multiple active components had high affinity with most core targets. CONCLUSION: SRS can treat FD through a variety of pathways, which provides a direction for the modern application of SRS in FD treatment.

"UHPLC-Q-TOF/MS-chemometrics-network pharmacology" integrated strategy to discover quality markers of raw and stir-fried Fructus Tribuli and process optimization of stir-fried Fructus Tribuli.

INTRODUCTION: Fructus Tribuli, the dried ripe fruit of Tribulus terrestris L., has various beneficial effects, including liver-calming and depression-relieving effects. Raw Fructus Tribuli (RFT) and stir-fried Fructus Tribuli (SFT) are included in the Chinese Pharmacopoeia 2020 edition (Ch. P 2020). However, owing to the lack of specific regulations on SFT-processing parameters in Ch. P 2020, it is difficult to ensure the quality of commercially available SFT. OBJECTIVE: The present study aimed to screen the quality markers (Q-markers) of RFT and SFT and optimize the processing technology of SFT based on the identified Q-markers. METHODS: First, the ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) technology as well as multiple statistical analysis along with network pharmacology was used to comprehensively identify the Q-markers of RFT and SFT. Then, based on single-factor experiments, the Box-Behnken design (BBD) response surface methodology (RSM) was used to optimize the processing technology of SFT and perform process validation. RESULTS: A total of 63 components were identified in RFT and SFT extracts. Terrestrosin D and Terrestrosin K were initially considered the Q-markers of RFT and SFT, respectively. The optimum processing technology conditions were 208°C, 14 min, and 60 r·min-1 . Three batches of process validation were performed, and the mean composite score was 56.87, with a relative standard deviation (RSD) value of 1.13%. CONCLUSION: The content of steroidal saponin components in RFT was significantly different before and after stir-frying. Terrestrosin D and Terrestrosin K were validated as the Q-markers of RFT and SFT, respectively. The identification of Q-markers for RFT and SFT offered a clear index for optimizing the SFT-processing technology and provided a basis for the quality control of RFT and SFT decoction pieces.

Angelica Sinensis Polysaccharide-Based Nanoparticles for Liver-Targeted Delivery of Oridonin.

The present work aimed to study the feasibility of Angelica sinensis polysaccharide (ASP) as an instinctive liver targeting drug delivery carrier for oridonin (ORI) in the treatment of hepatocellular carcinoma (HCC). ASP was reacted with deoxycholic acid (DOCA) via an esterification reaction to form an ASP-DOCA conjugate. ORI-loaded ASP-DOCA nanoparticles (ORI/ASP-DOCA NPs) were prepared by the thin-film water method, and their size was about 195 nm in aqueous solution. ORI/ASP-DOCA NPs had a drug loading capacity of up to 9.2%. The release of ORI in ORI/ASP-DOCA NPs was pH-dependent, resulting in rapid decomposition and accelerated drug release at acidic pH. ORI/ASP-DOCA NPs significantly enhanced the accumulation of ORI in liver tumors through ASGPR-mediated endocytosis. In vitro results showed that ORI/ASP-DOCA NPs increased cell uptake and apoptosis in HepG2 cells, and in vivo results showed that ORI/ASP-DOCA NPs caused effective tumor suppression in H22 tumor-bearing mice compared with free ORI. In short, ORI/ASP-DOCA NPs might be a simple, feasible, safe and effective ORI nano-drug delivery system that could be used for the targeted delivery and treatment of liver tumors.

Qualitative and quantitative analysis of the component variations of Raphani Semen during the stir-frying process and elucidation of transformation pathways of multiple components.

Raphani Semen (RS) encompasses two distinct application forms in Chinese clinical practice: raw RS (RRS) and stir-fried RS (SRS). They exhibit divergent drug properties and effects, as described in traditional Chinese medicine theory known as "Sheng shu yi zhi, sheng sheng shu jiang". The dissimilarity in RS's drug properties is intrinsically linked to alterations in its internal components during the stir-frying process. Previous studies have demonstrated that stir-frying renders myrosinase inactive, thereby preventing the enzymatic hydrolysis of glucosinolates in RS. However, the precise enzymatic hydrolysis pathway and products of glucosinolates remain unclear. Furthermore, it remains uncertain whether other components undergo changes influenced by endogenous enzymes. The objective of this study is to systematically analyze the chemical components disparities between RRS and SRS using high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-TOF-MS). Additionally, it seeks to elucidate the potential transformation pathways of multiple components from an enzymatic hydrolysis perspective. We have developed a sensitive and efficient high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC-QQQ-MS) method for quantifying the content of 5 characteristic components, including glucoraphenin, sinapine thiocyanate, sulforaphene, sinapic acid, and 3',6-disinapoylsucrose. Based on retention time and MS spectra, we have identified 19 characteristic components in both SRS and RRS, encompassing glucosinolates and sulfur-containing derivatives, oligosaccharide esters, and small-molecule phenolic acids. Notably, 18 of these components undergo changes during the enzymatic hydrolysis process, leading to the identification of 4 transformation pathways: glucoraphenin, 6-sinapoylglucoraphenin, 3',6-disinapoylsucrose and ß-D-(3,4-disinapoyl) furanofructosyl-α-D-(6-sinapisoyl) glucoside, along with 3'-O-sinapoyl-6-O-feruloylsucrose. Quantitative analysis reveals significant differences, including lower levels of glucoraphenin in RRS compared to SRS, higher sulforaphene and sinapic acid levels in RRS, while sinapine thiocyanate and 3',6-disinapoylsucrose remain unchanged before and after stir-frying. The results of this study highlight distinct chemical compositions between RRS and SRS. Additionally, the method of characterization and content determination constructed in this paper has strong practical value and provides a useful approach for comprehensively evaluating the chemical composition and quality of RS.

Study on the mechanism of stir-fried Fructus Tribuli in enhancing the essential hypertension treatment by an integrated "spectrum-effect relationship-network pharmacology-metabolomics" strategy.

Essential hypertension (EH) is a leading cause of cardiovascular morbidity and mortality. Fructus Tribuli (FT), as a traditional medicine, has been frequently used for thousands of years. The crude Fructus Tribuli (CFT), decoction pieces being processed to remove impurities, have been listed as an important medicine for the treatment of hypertension in the elderly. According to the theory of traditional Chinese medicine, the CFT can enhance the EH treatment after being stir-fried into stir-fried Fructus Tribuli (SFT). At present, whether the SFT can enhance the EH treatment and its potential pharmacodynamic substances and mechanism are unknown. In this study, an integrated "spectrum-effect relationship-network pharmacology-metabolomics" strategy was used. Using male spontaneously hypertensive rats as an experimental model, we compared the therapeutic effects of CFT and SFT on EH. Subsequently, to define the pharmacodynamic material basis of SFT in enhancing the EH treatment, the steroidal saponins (main active components of FT) were selected for spectrum-effect relationship analysis. Furthermore, we applied the joint pathway analysis of network pharmacology and metabolomics to explore the underlying mechanism of SFT in enhancing the EH treatment. Results showed that SFT was better than CFT in the EH treatment. The steroidal saponins transformed by stir-frying were the potential pharmacodynamic substances that SFT could enhance the EH treatment. And the mechanism of action might be associated with regulating glycerophospholipid metabolism and arachidonic acid metabolism, especially arachidonic acid metabolism. This study provided a scientific basis for the clinical use of SFT as an important medicine for the EH treatment.

Network pharmacology-based approach uncovers the pharmacodynamic components and mechanism of Fructus Tribuli for improving endothelial dysfunction in hypertension.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Tribuli (FT), a traditional Chinese medicinal herbal, has been used for the clinical treatment of cardiovascular diseases for many years and affects vascular endothelial dysfunction (ED) in patients with hypertension. AIM OF THE STUDY: This study aimed to demonstrate the pharmacodynamic basis and mechanisms of FT for the treatment of ED. MATERIALS AND METHODS: The present study used ultra-high-performance liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to analyze and identify the chemical components of FT. The active components in blood were determined after the oral administration of FT by comparative analysis to blank plasma. Then, based on the active components in vivo, network pharmacology was performed to predict the potential targets of FT in treating ED. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed, and component-target-pathway networks were constructed. Interactions between the major active components and main targets were verified by molecular docking. Moreover, spontaneously hypertensive rats (SHRs) were divided into the normal, model, valsartan, low-dose FT, medium-dose FT, and high-dose FT experimental groups. In pharmacodynamic verification studies, treatment effects on blood pressure, serum markers (nitric oxide [NO], endothelin-1 [ET-1,], and angiotensin Ⅱ [Ang Ⅱ)]) of ED, and endothelial morphology of the thoracic aorta were evaluated and compared between groups. Finally, the PI3K/AKT/eNOS pathway was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot of the thoracic aorta of rats in each group to detect the mRNA expression of PI3K, AKT, and eNOS and the protein expression of PI3K, AKT, p-AKT, eNOS, and p-eNOS. RESULTS: A total of 51 chemical components were identified in FT, and 49 active components were identified in rat plasma. Thirteen major active components, 22 main targets, and the PI3K/AKT signaling pathway were screened by network pharmacology. The animal experiment results showed that FT reduced systolic blood pressure and ET-1 and Ang Ⅱ levels and increased NO levels in SHRs to varying degrees. The therapeutic effects were positively correlated with the oral dose of FT. Hematoxylin-eosin (HE) staining confirmed that FT could alleviate the pathological damage of the vascular endothelium. qRT-PCR and Western blot analysis confirmed that up-regulated expression of the PI3K/AKT/eNOS signaling pathway could improve ED. CONCLUSIONS: In this study, the material basis of FT was comprehensively identified, and the protective effect on ED was confirmed. FT had a treatment effect on ED through multi-component, multi-target, and multi-pathways. It also played a role by up-regulating the PI3K/AKT/eNOS signaling pathway.

Extraction, purification, structure characteristics, biological activities and pharmaceutical application of Bupleuri Radix Polysaccharide: A review.

Bupleuri Radix (BR), as a well-known plant medicine of relieving exterior syndrome, has a long history of usage in China. Bupleuri Radix Polysaccharide (BRP), as the main component and an important bioactive substance of BR, has a variety of pharmacological activities, including immunoregulation, antioxidant, antitumor, anti-diabetic and anti-aging, etc. In this review, the advancements on extraction, purification, structure characteristics, biological activities and pharmaceutical application of BRP from different sources (Bupleurum chinense DC., Bupleurum scorzonerifolium Willd., Bupleurum falcatum L. and Bupleurum smithii Woiff. var. Parvifolium Shan et Y. Li.) are summarized. Meanwhile, this review makes an in-depth discussion on the shortcomings of the research on BRP, and new valuable insights for the future researches of BRP are proposed.

Strategies for Solubility and Bioavailability Enhancement and Toxicity Reduction of Norcantharidin.

Cantharidin (CTD) is the main active ingredient isolated from Mylabris, and norcantharidin (NCTD) is a demethylated derivative of CTD, which has similar antitumor activity to CTD and lower toxicity than CTD. However, the clinical use of NCTD is limited due to its poor solubility, low bioavailability, and toxic effects on normal cells. To overcome these shortcomings, researchers have explored a number of strategies, such as chemical structural modifications, microsphere dispersion systems, and nanodrug delivery systems. This review summarizes the structure-activity relationship of NCTD and novel strategies to improve the solubility and bioavailability of NCTD as well as reduce the toxicity. This review can provide evidence for further research of NCTD.

Elucidation of active ingredients and mechanism of action of hawthorn in the prevention and treatment of atherosclerosis.

Hawthorn (HT), a functional food and medicinal herb for centuries in China, has potential preventive and therapeutic effects on atherosclerosis (AS). However, the mechanisms and active ingredients of HT in the prevention and treatment of AS are unclear. This study aimed to reveal active components and mechanism of HT in the prevention and treatment of AS using UHPLC-Q-Exactive Orbitrap MS and network pharmacology. A total of 50 compounds were identified by UHPLC-Q-Exactive Orbitrap MS. Six core targets and six active compounds were obtained by network pharmacology. Apigenin, luteolin, chrysin, quercetin, oleanic acid, and corosolic acid were the active components in the prevention and treatment of AS, and core targets included SRC, HSP90AA1, MAPK3, EGFR, HRAS, and AKT1. The key signaling pathways involved are MAPK, HIF-1, NF-kappa B, PI3K-Akt, TNF, Rap1, Ras, and VEGF signaling pathways. Further molecular docking results indicated that the six active compounds had strong hydrogen bonding ability with the six core targets. On the molecular level, HT may regulate AS by controlling cell survival and proliferation, reducing the levels of enzymes HMG-CoA reductase and lipoprotein lipase and inhibiting inflammatory response. PRACTICAL APPLICATIONS: HT can serve as "medicine-food homology" for dietary supplement and exert potential preventive and therapeutic effects on AS. However, the mechanisms of HT in the prevention and treatment of AS are unclear. This study describes a rapid method of detecting and identifying the components and mechanism of HT based on LC-MS and network pharmacology, which provides a theoretical and scientific support for further application of HT and guidance for the research of other herbal medicines.

Nano-drug co-delivery system of natural active ingredients and chemotherapy drugs for cancer treatment: a review.

Chemotherapy drugs have been used for a long time in the treatment of cancer, but serious side effects are caused by the inability of the drug to be solely delivered to the tumor when treating cancer with chemotherapy. Natural products have attracted more and more attention due to the antitumor effect in multiple ways, abundant resources and less side effects. Therefore, the combination of natural active ingredients and chemotherapy drugs may be an effective antitumor strategy, which can inhibit the growth of tumor and multidrug resistance, reduce side effects of chemotherapy drugs. Nano-drug co-delivery system (NDCDS) can play an important role in the combination of natural active ingredients and chemotherapy drugs. This review provides a comprehensive summary of the research status and application prospect of nano-delivery strategies for the combination of natural active ingredients and chemotherapy drugs, aiming to provide a basis for the development of anti-tumor drugs.

Traditional uses, phytochemistry, transformation of ingredients and pharmacology of the dried seeds of Raphanus sativus L. (Raphani Semen), A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Raphani Semen (Lai Fu-zi in Chinese, RS), the dried seeds of Raphanus sativus L., is a traditional Chinese herbal medicine. RS has long been used for eliminating bloating and digestion, antitussive, expectorant and anti-asthmatic in clinical treatment of traditional Chinese medicine. AIM OF THE STUDY: This review provides a critical and comprehensive summary of traditional uses, phytochemistry, transformation of ingredients and pharmacology of RS based on research data that have been reported, aiming at providing a basis for further study on RS. MATERIALS AND METHODS: The search terms "Raphani Semen", "the seeds of Raphanus sativus L." and "radish seed" were used to obtain the information from electronic databases such as Web of Science, China National Knowledge Infrastructure, PubMed and other web search instruments. Traditional uses, phytochemistry, transformation of ingredients and pharmacology of RS were summarized. RESULTS: RS has been traditionally used to treat food dyspeptic retention, distending pain in the epigastrium and abdomen, constipation, diarrhea and dysentery, panting, and cough with phlegm congestion in the clinical practice. The chemical constituents of RS include glucosinolates and sulfur-containing derivatives, phenylpropanoid sucrosides, small organic acids and derivatives, flavone glycosides, alkaloids, terpenoids, steroids, oligosaccharides and others. Among them, glucosinolates can be transformated to isothiocyanates by plant myrosinase or the intestinal flora, which display a variety of activities, such as anti-tumor, anti-inflammatory, antioxidant, antibacterial, treatment of metabolic diseases, central nervous system protection, anti-osteoporosis. RS has a variety of pharmacological activities, including treatment of metabolic diseases, anti-inflammatory, anti-tumor, antioxidant, antibacterial, antihypertensive, central nervous system protection, anti-osteoporosis, etc. This review will provide useful insight for exploration, further study and precise medication of RS in the future. CONCLUSIONS: According to its traditional uses, phytochemistry, transformation of ingredients and pharmacology, RS is regarded as a promising medical plant with various chemical compounds and numerous pharmacological activities. However, the material bases and mechanisms of traditional effect of RS need further study.

Dietary fructose intake is correlated with fat distribution in the Newfoundland population.

OBJECTIVE: Increased dietary fructose intake is associated with elevated body weight and body mass index. Few studies are available regarding the relationship between fat distribution and dietary fructose intake. The aim of this study was to investigate the association between dietary fructose intake and fat distribution in adults in a large Newfoundland cohort. METHODS: We analyzed 2298 adults from CODING (Complex Diseases in the New found land Population: Environment and Genetics) study. Intake of dietary fructose was evaluated from the Willett food frequency questionnaire. Fat distribution was estimated by dual-energy x-ray absorptiometry. Partial correlation analysis was used to determine the correlations of dietary fructose intake with fat distribution adjusted for major confounding factors. RESULTS: Daily dietary fructose intake was negatively associated with arm fat in postmenopausal women (r = -0.080, P < 0.05), but positively associated with arm fat in premenopausal women after adjusting for age, total calorie intake, and physical activity levels (r = 0.079, P < 0.05). Dietary fructose intake was negatively correlated with both arm fat (r = -0.131, P < 0.05) and visceral fat (r = -0.124 measured in mass, r = -0.124 measured in volume respectively; P < 0.05) in men <45 y of age, not in men ≥45 y. CONCLUSION: This study demonstrated that dietary fructose intake is significantly correlated with arm fat in both women and men, and visceral fat in men in the Newfoundland free-living population. The correlations are sex- and menopause-status dependent.

Extraction, structure, pharmacological activities and drug carrier applications of Angelica sinensis polysaccharide.

Angelica sinensis polysaccharide (ASP) is one of the main active components of Angelica sinensis (AS) that is widely used in traditional Chinese medicine. ASP is water-soluble polysaccharides, and it is mainly composed of glucose (Glc), galactose (Gal), arabinose (Ara), rhamnose (Rha), fucose (Fuc), xylose (Xyl) and galacturonic acid (GalUA). The extraction methods of ASP include hot water extraction and ultrasonic wave extraction, and different extraction methods can affect the yield of ASP. ASP has a variety of pharmacological activities, including hematopoietic activity, promoting immunity, antitumor, anti-inflammatory, antioxidant, anti-aging, anti-virus, liver protection, and so on. As a kind of natural polysaccharide, ASP has potential application as drug carriers. This review provides a comprehensive summary of the latest extraction and purification methods of ASP, the strategies used for monosaccharide compositional analysis plus polysaccharide structural characterization, pharmacological activities and drug carrier applications, and it can provide a basis for further study on ASP.

Study on the Potential Mechanism of Fructus Tribuli in the Treatment of Hypertensive Vascular Remodeling Based on Network Pharmacology and Molecular Docking.

BACKGROUND: Hypertensive vascular remodeling (HVR) is the pathophysiological basis of hypertension, which is also an important cause of vascular disease and target organ damage. Treatment with Fructus Tribuli (FT), a traditional Chinese medicine, has a positive effect on HVR. However, the pharmacological mechanisms of FT are still unclear. Therefore, this study aimed to reveal the potential mechanisms involved in the effects of FT on HVR based on network pharmacology and molecular docking. MATERIALS AND METHODS: We selected the active compounds and targets of FT according to the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Swiss Target Prediction database, and the targets of HVR were collected from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and DrugBank databases. The protein-protein interaction network (PPI) was established using the STRING database. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and network analysis were performed to further explore the potential mechanisms. Finally, molecular docking methods were used to evaluate the affinity between the active compounds and the main target. RESULTS: Seventeen active compounds of FT and 164 potential targets for the treatment of HVR were identified. Component-target and PPI networks were constructed, and 12 main active components and 33 main targets were identified by analyzing the topological parameters. Additionally, GO analysis indicated that the potential targets were enriched in 483 biological processes, 52 cellular components, and 110 molecular functions. KEGG analysis revealed that the potential targets were correlated with 122 pathways, such as the HIF-1 signaling pathway, ErbB signaling pathway, and VEGF signaling pathway. Finally, molecular docking showed that the 12 main active components had a good affinity for the top five main targets. CONCLUSION: This study demonstrated the multiple compounds, targets, and pathway characteristics of FT in the treatment of HVR. The network pharmacology method provided a novel research approach to analyze potential mechanisms.

Novel Strategies for Solubility and Bioavailability Enhancement of Bufadienolides.

Toad venom contains a large number of bufadienolides, which have a variety of pharmacological activities, including antitumor, cardiovascular, anti-inflammatory, analgesic and immunomodulatory effects. The strong antitumor effect of bufadienolides has attracted considerable attention in recent years, but the clinical application of bufadienolides is limited due to their low solubility and poor bioavailability. In order to overcome these shortcomings, many strategies have been explored, such as structural modification, solid dispersion, cyclodextrin inclusion, microemulsion and nanodrug delivery systems, etc. In this review, we have tried to summarize the pharmacological activities and structure-activity relationship of bufadienolides. Furthermore, the strategies for solubility and bioavailability enhancement of bufadienolides also are discussed. This review can provide a basis for further study on bufadienolides.

Preparation of oridonin nanocrystals and study of their endocytosis and transcytosis behaviours on MDCK polarized epithelial cells.

Context: Oridonin (ORI) has obvious anticancer effects, but its solubility is poor. Nanocrystal (NC) is a novel nano-drug delivery system for increasing bioavailability for ORI. However, the endocytosis and transcytosis behaviours of oridonin nanocrystals (ORI-NCs) through epithelial membrane are still unclear.Objectives: ORI-NCs were prepared and characterized. The in vitro cytotoxicity and endocytosis and transcytosis process on Madin-Darby canine kidney (MDCK) monolayer were investigated.Materials and methods: Anti-solvent precipitation method was adopted in preparation of ORI-NCs. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were adopted to explore crystallography of ORI-NCs. Sulforhodamine B (SRB) method was used to test the inhibition effect on proliferation of MDCK cells. Quantitative analysis by HPLC was performed to study the endocytosis and transcytosis of ORI-NCs and ORI bulk drug, and the process was observed by confocal laser spectrum microscopy (CLSM) and flow cytometry.Results: The particle size of ORI-NCs was about 274 nm. The crystallography form of ORI was not changed after prepared into NCs. The dissolution rate of ORI-NCs was higher than pure ORI in 120 min. At higher concentrations (34, 84 and 135 µg/mL), ORI-NCs significantly reduced the cell viability compared with free ORI (p < 0.05, p < 0.01). ORI-NCs demonstrated higher endocytosis in MDCK cells than free ORI (p < 0.01). In the transport process, ORI-NC was taken up into cells in an intact form, and excreted out from basolateral membrane of polarized epithelial cells in an intact form. The internalization and transmembrane amount increased as a function of time.Conclusions: ORI-NCs transported through the MDCK monolayers in an intact form.

Solubility and Bioavailability Enhancement of Oridonin: A Review.

Oridonin (ORI), an ent-kaurene tetracyclic diterpenoid compound, is isolated from Chinese herb Rabdosia rubescens with various biological and pharmacological activities including anti-tumor, anti-microbial and anti-inflammatory effects. However, the clinical application of ORI is limited due to its low solubility and poor bioavailability. In order to overcome these shortcomings, many strategies have been explored such as structural modification, new dosage form, etc. This review provides a detailed discussion on the research progress to increase the solubility and bioavailability of ORI.

Stimuli-responsive charge-reversal nano drug delivery system: The promising targeted carriers for tumor therapy.

The stimuli-responsive charge-reversal nano drug delivery system (CRNDDS) for the treatment of tumors has attracted much attention as an effective drug delivery system. The charge-reversal nanocarriers are either uncharged or negatively charged under normal physiological environment; however, they acquire positive charged in tumor tissue microenvironment. The process of charge reversal from negative-to-positive results in not only quick drug release in acidic environment but also enhance the cellular uptake of drug through electrostatic absorptive endocytosis resulting in improvement of cancer therapeutic outcome. In this review, we discuss the recent advances in the study of charge-reversal nanocarriers that could control the distribution of drugs in response to specific stimuli, such as pH, reduced glutathione (GSH) concentration, enzyme concentration, light and thermal stimulation. The applications of CRNDDS in the tumor treatment was also analyzed and summarized.

[Studies on separation and purification of Rhizoma Fagopyri Dibotoryis extract by macroporous resin].

OBJECTIVE: To establish a technical process for purification of extract of Rhizoma Fagopyri Dibotoryis. METHOD: The static adsorption capacity and elution ratio of Mixture of proanthocyanidins tannic condensation were used as evaluation to select the best resin in 3 kinds of macroporous resin. The adsorptive characteristics and elution parameters of selected resin were studied. RESULT: D-101 resin had good separation performance and was suited to purify priceid in extract of Rhizoma Fagopyri Dibotoryis. CONCLUSION: The process of applying macroporous resin to absorb and purity priceid in extract of Rhizoma Fagopyri Dibotoryis is feasible.