Formulation design and characterization of silymarin liposomes for enhanced antitumor activity.

Liposomes, a nanoscale carrier, plays an important role in the delivery of drug, affects the in vivo efficacy of drugs. In this paper, silymarin(SM)-loaded liposomes was optimized using the response surface method (RSM), with entrapment efficiency (EE%) as an index. The formulation was optimized as follow: lecithin (7.8mg/mL), SM/lecithin (1/26) and lecithin/cholesterol (10/1). The optimized SM liposomes had a high EE (96.58 ±3.06%), with a particle size of 290.3 ±10.5nm and a zeta potential of +22.98 ±1.73mV. In vitro release tests revealed that SM was released in a sustained-release manner, primarily via diffusion mechanism. In vitro cytotoxicity studies demonstrated that the prepared SM liposomes had stronger inhibitory effects than the model drug. Overall, these results indicate that this liposome system is suitable for intravenous delivery to enhance the antitumor effects of SM.

Design and characterization of gambogic acid-loaded mixed micelles system for enhanced oral bioavailability.

The aim of this study was to develop a gambogic acid-loaded mixed micelles (GA-M) system, using Kolliphor HS15 and lecithin, for enhancement of oral bioavailability. GA-M was prepared using the thin film hydration method, and particle size and zeta potential indexes were used to determine the optimized formulation was optimized with taking particle size, zeta potential as indexes. The optimal GA-M system had a mean particle size in the nanometer range (87.22 ± 0.68 nm) and zeta potential greater than 20 mV in magnitude (-21.63 ± 1.69 mV) at a 1:1 proportion of HS15: lecithin. Additionally, the carriers had a high entrapment efficiency (98.32 ± 3.52%) and drug loading (4.68 ± 0.17%). Furthermore, the in vitro GA release characteristics followed first-order kinetics, suggesting that the release of the molecule was achieved both by medium diffusion and structural erosion. Transport elucidation in Caco-2 cells demonstrated that the efflux ratio of encapsulated GA was dramatically decreased from 1.42 to 0.76, and pharmacokinetic studies showed that the oral bioavailability of GA-M was 2.3 times higher than that of free GA, indicating that HS15/lecithin mixed micelles could promote absorption in the gastrointestinal tract. Overall, these results present a micelle system suitable for oral delivery, with increased solubility and oral bioavailability of GA.

[Research progress on camptothecin and its derivative nano-prodrugs based on tumor microenvironment response].

Nano-prodrug, one of the most widely used nano-formulation at present, has excellent efficacies in tumor treatment with high potential and clinical value. Camptothecin and its derivatives have broad prospects in the preparation of prodrugs for the treatment of tumors. Given the special microenvironment of tumors, including partial acidity, high concentration of reactive oxygen species, high concentration of glutathione and enzyme concentration, a large number of tumor microenvironment-responsive camptothecin and its derivative prodrugs were prepared. This paper classified them from the microenvironment response types and drug release characteristics, reviewed the research progress of camptothecin and its derivative prodrugs based on safety and clinical trials, and analyzed the existing problems and deficiencies, hoping to provide references for the development of camptothecin and its derivatives.

Facile Construction and Fabrication of a Superhydrophobic and Super Oleophilic Stainless Steel Mesh for Separation of Water and Oil.

The fluoride-free fabrication of superhydrophobic materials for the separation of oil/water mixtures has received widespread attention because of frequent offshore oil exploration and chemical leakage. In recent years, oil/water separation materials, based on metal meshes, have drawn much attention, with significant advantages in terms of their high mechanical strength, easy availability, and long durability. However, it is still challenging to prepare superhydrophobic metal meshes with high-separation capacity, low costs, and high recyclability for dealing with oil-water separation. In this work, a superhydrophobic and super oleophilic stainless steel mesh (SSM) was successfully prepared by anchoring Fe2O3 nanoclusters (Fe2O3-NCs) on SSM via the in-situ flame synthesis method and followed by further modification with octadecyltrimethoxysilane (OTS). The as-prepared SSM with Fe2O3-NCs and OTS (OTS@Fe2O3-NCs@SSM) was confirmed by a field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), energy dispersive spectrometer (EDS), X-ray photoelectron spectrometer (XPS), and X-ray diffractometer (XRD). The oil-water separation capacity of the sample was also measured. The results show that the interlaced and dense Fe2O3-NCs, composed of Fe2O3 nanoparticles, were uniformly coated on the surface of the SSM after the immerging-burning process. Additionally, a compact self-assembled OTS layer with low surface energy is coated on the surface of Fe2O3-NCs@SSM, leading to the formation of OTS@Fe2O3-NCs@SSM. The prepared OTS@Fe2O3-NCs@SSM shows excellent superhydrophobicity, with a water static contact angle of 151.3°. The separation efficiencies of OTS@Fe2O3-NCs@SSM for the mixtures of oil/water are all above 98.5%, except for corn oil/water (97.5%) because of its high viscosity. Moreover, the modified SSM exhibits excellent stability and recyclability. This work provides a facile approach for the preparation of superhydrophobic and super oleophilic metal meshes, which will lead to advancements in their large-scale applications on separating oil/water mixtures.

Corrigendum: Beneficial Effects and Toxicity Studies of Xian-ling-gu-bao on Bone Metabolism in Ovariectomized Rats.

[This corrects the article DOI: 10.3389/fphar.2017.00273.].

[Characterization of oil/water partition coefficient of chishao terpene glucoside components based on contribution rate of representative components for myocardial ischemia].

The components of traditional Chinese medicine(TCMCs) are the basic unit of raw materials for Chinese medicines, and their physical and chemical properties directly affect the choice of dosage forms and the optimization of prescriptions. However, most of TCMCs are multi-component complex systems, and the characterization of their overall properties is still in the exploration stage. On the basis of biological activity, the representative components are determined, and then the individual characteristics are fitted with the weight coefficient of efficacy contribution rate, which may provide reference for characterizing the overall properties of TCMCs. In this study, with the pharmacological effects of isoproterenol(ISO)-induced myocardial ischemia in rats as the indicators, the pharmacodynamic contribution rates of three representative components of chishao terpene glucoside components(CSTGCs) were evaluated by the normalization weighting method. The contribution rates of paeoniflorin, paeoniflorin and benzoylpaeoniflorin were 54.87%, 32.46% and 12.67%, respectively. The oil-water partition coefficients of paeoniflorin, albiflorin, benzoylpaeoniflorin in water and buffer solutions with different pH values were measured, and the oil-water partition coefficients of CSTGCs were characterized by the weight of their pharmacodynamics contribution rate. The results showed that the apparent oil-water partition coefficient(log P) of CSTGCs in the phosphate buffer system such as n-octanol-water(pH 2.0, 2.5, 5.0, 5.8, 6.8) were 0.18-0.22, indicating that CSTGCs have common absorption and low permeability, providing basis for the preparation of CSTGCs.

[Preparation method and pharmacological effect of baohuoside â ].

Epimedii Folium, a famous traditional Chinese medicine made of dried leaves of Epimedium brevicomu, E. pubescens, E. sagittatum or E. koreanum, has been applied in China for several thousand years as a medicine. It has the function of reinforcing kidney Yang, strengthening muscles and bones and dispelling rheumatism. Modern studies have shown that baohuoside Ⅰ has a low content in Herba Epimedii, but it has a wide range of pharmacological effects, such as anti-osteoporosis, anti-tumor, improving cognitive dysfunction, cerebral ischemia-reperfusion injury protection, and neuroprotection. More and more attention has been paid to the preparation methods and pharmacological effects of baohuoside Ⅰ due to its many biological activities and pharmacological effects. In this present research, in order to provide references for the better mass preparation and rational exploitation of baohuoside Ⅰ, we summarized and sorted out the preparation methods and pharmacological effects of baohuoside Ⅰ which were published in recent years.

Lactone Component From Ligusticum chuanxiong Alleviates Myocardial Ischemia Injury Through Inhibiting Autophagy.

The dysregulation of autophagy is associated with a series of cardiovascular diseases, such as myocardial ischemia injury. Lactone component from Ligusticum chuanxiong (LLC) is the major constituent of the traditional Chinese herb L. chuanxiong Hort., which has been reported to hold potential cardioprotective effects. In this study, to determine whether LLC protects the heart through regulation of autophagy, we explored the effects of LLC on cardioprotection and autophagy in myocardial ischemia injured rats and H9c2 cardiomyocytes. Our results showed that LLC significantly reduced infarct size and serum levels of lactate dehydrogenase, creatine kinase, and cardiac troponin and ameliorated histological features in a dose-dependent manner. Similar protections were observed in cardiomyocytes subjected to oxygen-glucose deprivation (OGD). Meanwhile, LLC inhibited autophagy induced by myocardial ischemia injury, characterized by increased autophagic vacuoles, LC3-II/LC3-I ratio and the expression of Beclin 1, whereas decreased the expression of p62. Additionally, LLC combined with a lysosomal inhibitor chloroquine (CQ) reduced LC3-II/LC3-I ratio in cardiomyocytes compared with CQ alone. Furthermore, LLC-afforded cardioprotection was abolished by a specific PI3K inhibitor LY294002. Collectively, these findings demonstrated that cardioprotective effects of LLC were related to restoration of autophagic flux through the activation of PI3K/Akt/mTOR signaling pathway.

Evaluation of in vitro and in vivo antitumor effects of gambogic acid-loaded layer-by-layer self-assembled micelles.

This study aimed to develop a novel type of multilayer micelle using protamine (PRM) and hyaluronic acid (HA) for the delivery of gambogic acid (GA). GA-loaded micelles (GA-M) were simply andrapidly prepared using lecithin/solutol HS15 using a film-dispersion method. PRM and HA were added in sequence to form layer-by-layer self-assembled micelles (HA-PRM-GA-M), in which particle size, zeta potential, particle morphology, drug loading, encapsulation efficiency, and in vitro release were investigated. Surface charge reversal demonstrated that rapid HA detachment exposed PRM, leading to activation of a "proton sponge" effect in the hyaluronidase (HAase)-rich tumor microenvironment. Compared with coumarin 6-loaded micelles (C6-M), more efficient intracellular trafficking was observed for HA-PRM-C6-M, which is associated with the endosomal/lysosomal escaping ability of the exposed PRM. In vivo imaging showed increased enrichment of near infrared fluorescent dye (DIR)-loaded HA-PRM-DIR-M at the tumor site, suggesting that HA enhanced the active tumor targeting of GA. Furthermore, HA-PRM-GA-M showed the stronger antitumor activity than GA and GA-M against human lung adenocarcinoma (A549) tumor xenografts in nude mice. In summary, our findings show the potential of HA-PRM-GA-M as a novel intravenous drug carrier for the treatment of lung cancer.

[Characterization of overall biopharmaceutical properties of traditional Chinese medicine components based on identification of representational components].

Preformulation research, an in-depth research for pharmacological and pharmaceutical properties of raw materials, has been widely used in the field of chemical drugs. Although traditional Chinese medicine components (TCMCs) are the basic units in Chinese medicine preparation, the properties characterization of these components is still in an exploratory stage, because empiricism and blindness are still present in the development of the Chinese medicine preparations. TCMCs, a complex multi-component system, is very difficult to be analyzed in details. Herein, a research idea is put forward for the characterization of overall properties by using representative compositions. Firstly, various composition groups were set up for screening the representative components by in vitro and in vivo efficacy evaluation according to the original proportion. Then the equilibrium solubility, oil/water (O/W) partition coefficient and apparent permeability coefficient of the representative components were detected. Subsequently, the similarity assessment and discrete analysis were performed for the subdivision of TCMCs. The overall properties of TCMCs were fitted by mass fraction or efficacy contribution of each representative component, so as to characterize the overall properties of components/sub-components.

[Discussion on influence factors, mechanism and traditional Chinese medicine pathogenesis of idiosyncratic drug-induced liver injury].

Idiosyncratic drug-induced liver injury (IDILI) is a kind of unique adverse drug reaction with relative high morbidity compared with other idiosyncratic diseases. Its occurrence, however, has nothing to do with pharmacological effects and clinical dosage of drugs administered, and only a small number of susceptible individuals will suffer from it. Especially to deserve to be mentioned, the proportion of TCM-induced IDILI showed an ascending trend year by year. So in this article, the author has reviewed some facts related with TCM-induced IDILI, including the predisposing causes and occurrence mechanism, and tries to provide reference for the prevention, diagnosis and treatment of TCM-induced IDILI through the analysis of characteristics and research status of TCM-induced IDILI and exploration of the internal relationship between Chinese medicine constitution type and IDILI.

Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer.

Ginsenoside compound K (CK) is one of the effective ingredients in antitumor composition of ginsenoside. However, the poor water solubility and significant efflux have limited the widespread clinical use of CK. In this study, preparation of novel CK-loaded d-alpha-tocopheryl polyethylene glycol 1,000 succinate/poly(ethylene glycol)-poly(ε-caprolactone) mixed micelles (CK-M) is discussed to solve the above problems. Particle size, zeta potential, and morphology were characterized using dynamic light scattering and transmission electron microscopy. CK-M are spherical shaped with an average particle size of 53.07±1.31 nm with high drug loading of 11.19%±0.87% and entrapment efficiency of 94.60%±1.45%. Water solubility of CK was improved to 3.78±0.09 mg/mL, which was ~107.35 times higher than free CK. A549 and PC-9 cells were used to evaluate in vitro cytotoxicity and cellular uptake. IC50 values of CK-M in A549 and PC-9 cells (24 h) were 25.43±2.18 and 18.35±1.90 µg/mL, respectively. Enhanced cellular uptake of CK-M was observed in both cells. Moreover, CK-M promoted tumor cell apoptosis, inhibited tumor cell invasion, metastasis, and efflux through regulation of Bax, Bcl-2, matrix metalloproteinase-2, Caspase-3, and P-glycoprotein. In vivo imaging indicated that CK-M has excellent tumor targeting effect within 24 h, and the relative tumor inhibition rate of CK-M was 52.04%±4.62% compared with control group (P<0.01). Thus, CK-M could be an appropriate delivery agent for enhanced solubility and antitumor effect of CK.

Beneficial Effects and Toxicity Studies of Xian-ling-gu-bao on Bone Metabolism in Ovariectomized Rats.

Xian-ling-gu-bao (XLGB) is a well-known patented traditional Chinese prescription widely used to treat osteoporosis, osteoarthritis, aseptic bone necrosis, or climacteric syndrome. However, recent reports have suggested that XLGB may cause liver injury in humans. In the present study, we aimed to evaluate the efficacy of XLGB in the prevention of osteoporosis in the zebrafish and ovariectomized (OVX) rats, both of which have been used as osteoporosis models. The safety of XLGB after long-term administration to OVX rats was also assessed. OVX rats were administered by oral gavage 270 mg/kg (recommended daily dose), 1350 mg/kg, and 1800 mg/kg of XLGB for 26 weeks. Bone mineral density, relative bone surface to bone volume, relative bone volume to total volume, trabecular number, mean trabecular thickness, and mean trabecular spacing in OVX rats were examined at the end of the 26-week dosing period. Additionally, OPG and RANKL expression in the femur were determined by western blot and immunohistochemical staining. To evaluate the safety of XLGB, body weight, hematology, serum biochemistry markers related to toxicology, and organ histopathology were determined in each group of OVX rats. Conversely, the zebrafish was treated with prednisolone to induce osteoporosis in the embryo. Disodium etidronate was used as a treatment control. XLGB was shown to be effective in preventing osteoporosis in both the OVX rats and the prednisolone-treated zebrafish. Similarly, XLGB increased OPG protein and decreased RANKL protein in OVX rats. Interestingly, no obvious toxicity was observed in the heart, liver, kidney, small intestine, or stomach at dosages of up to 1800 mg/kg after treating the OVX rats for 26 weeks. XLGB was shown to be very effective in treating osteoporosis in OVX rats. No obvious toxicity or adverse effects developed in OVX rats at dosages up to 1800 mg/kg, which is equivalent to six times the daily-recommended dose. Therefore, XLGB should be considered a good option for the treatment of post-menopausal osteoporosis.

Crude terpene glycoside component from Radix paeoniae rubra protects against isoproterenol-induced myocardial ischemic injury via activation of the PI3K/AKT/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix paeoniae rubra, also known as chishao (CS), is a frequently used traditional Chinese medicine that can promote blood circulation to remove blood stasis. It has been widely used for the prevention and treatment of cardiovascular diseases in China. Although terpene glycoside (TG), the major component in CS, has been shown to possess cardioprotective properties, the mechanism underlying CS-TG's preventive effect against myocardial ischemia injury is unknown. This study was conducted to explore the protective and curative effects of CS-TG against isoproterenol (ISO)-induced myocardial ischemic injury in rats and investigate the underlying myocardial protective mechanisms. MATERIALS AND METHODS: A rat model of ISO-induced myocardial ischemia was established to evaluate the protective effect of CS-TG in ameliorating heart injury. Myocardial ischemia was induced by administering ISO (40mg/kg/d) subcutaneously for 2 days. Serum was collected and analyzed for the levels of different cardiac biomarkers, and heart tissues were isolated and prepared for ATP analysis, glycogen content determination, histopathology assay, and ultrastructure observation. The regulatory effects of CS-TG on myocardial apoptosis in rats were studied by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the levels of cleaved caspase-3, Bax, and Bcl-2 were detected by western blotting. Furthermore, in vitro experiments were conducted to examine whether the CS-TG's cardioprotective effects were linked to the inhibition of apoptosis via activation of the phosphoinositide-3-kinase/serine-threonine kinase AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. RESULTS: CS-TG (300mg/kg/d) significantly decreased serum levels of creatine kinase and lactate dehydrogenase in ISO-induced myocardial ischemic rats. Analysis of ATP and glycogen contents, myocardial ultrastructure, and pathological examination showed that CS-TG (300mg/kg/d) significantly improved energy metabolism and alleviated myocardial injury in vivo. In addition, the expression of p-AKT and p-mTOR in rats subjected to CS-TG significantly elevated, while the levels of caspase-3 and Bax/Bcl-2 dramatically reduced. Moreover, treatment with LY294002, a PI3K inhibitor, abrogated CS-TG (200µg/mL) induced down-regulation of cleaved caspase-3, Bax/Bcl-2 in the serum. CONCLUSIONS: CS-TG protects the heart from ISO-induced myocardial ischemia, potentially by improving cardiac energy metabolism and inhibiting cardiomyocyte apoptosis via activation of the PI3K/AKT/mTOR signaling pathway. Thus, CS -TG might be a potential therapeutic candidate for the prevention and treatment of myocardial ischemia.

Improved oral absorption and anti-lung cancer activity of paclitaxel-loaded mixed micelles.

The aim of this study was to establish a paclitaxel (PTX)-loaded mixed micelle delivery system (PTX-TP-M) with vitamin E-TPGS (TPGS) and Plasdone®S-630 Copovidone (PVPS630) as carriers to improve the solubility, oral absorption, and anti-tumor activity of PTX against lung cancer. In this study, PTX-TP-M was prepared using the ethanol thin-film dispersion method followed by characterization of the binary mixed micelles system. The average size of the PTX-TP-M was 83.5 ± 1.8 nm with a polydispersity index of 0.265 ± 0.007 and the drug loading (DL%) and entrapment efficiency (EE%) were 3.09 ± 0.09% and 95.67 ± 2.84%, respectively, which contributed to a high solubility of PTX about 24947-fold increase in water (4.78 ± 0.14 mg/mL). In addition, TEM analysis showed that the PTX-TP-M appeared spherical in structure and was well dispersed without aggregation and adhesion. In vitro release studies showed that the PTX-TP-M displayed a sustained release compared to free PTX in the dialysis bag. The efflux ratio of PTX reduced from 44.83 to 3.52 when formulated as PTX-TP-M; a 92.15% reduction, studied using the Caco-2 monolayer model. The oral bioavailability of PTX also improved by 4.35-fold, suggesting that PTX-TP-M can markedly promote the absorption in the gastrointestinal tract. Using in vitro MTT assays, it was observed that cytotoxicity was markedly increased, and IC50 values of PTX-TP-M (3.14 ± 0.85 and 8.28 ± 1.02 µg/mL) were lower than those of PTX solution (5.21 ± 0.93 and 14.53 ± 1.96 µg/mL) in A549 and Lewis cell, respectively. In vivo anti-tumor studies showed that PTX-TP-M achieved higher anti-tumor efficacy compared with PTX in Lewis bared C57BL/6 mice. Furthermore, a gastrointestinal safety assay also proved the safety of PTX-TP-M. All results demonstrated that the PTX-TP-M exhibited great potential for delivering PTX with increased solubility, oral bioavailability, and anti-cancer activity and this binary mixed micelles drug delivery system has potential to be used clinically.

Optimization and evaluation of Oridonin-loaded Soluplus®-Pluronic P105 mixed micelles for oral administration.

In this study, a new type of mixed micelles was developed using Soluplus® (SOL) and Pluronic® P105 (P105) for the encapsulation of Oridonin (ORN). Oridonin-loaded micelles (ORN-M) were simply prepared using solvent evaporation and characterized for particle size, particle morphology, encapsulation efficiency, and drug loading. In addition, the in vitro drug release behavior of ORN-M was assessed using the widely applied dialysis bag technique. The pharmacokinetic property of ORN was explored in rats after oral administration of ORN-M. Optimized ORN-M were of a small size (137.2±1.65nm) and spherical shape when the ratio of SOL:P105 was 3:1, with entrapment efficiency 90.48±1.85% and drug loading 15.08±0.38%. Oral absorption capacity of ORN was greatly enhanced with a relative bioavailability of 210.55% in comparison to that of in-house suspensions, which suggests that ORN-M shows significantly improved bioavailability and drug absorption characteristics. Overall, the optimized SOL-P105 dual mixed micelles show great potential for use as oral drug carriers for cancer treatment.

[Prevention effect of Ligusticum chuanxiong extraction against oxidative stress injury induced by myocardial ischemia through activation of Nrf2 signaling pathway].

Ligusticum chuanxiong is one of the common traditional Chinese medicinal herbs for treating various cardiovascular and cerebrovascular diseases, and a number of previous studies have demonstrated that the extract of L. chuanxiong has strong antioxidative activity. This paper was mainly aimed to investigate the effects and possible mechanisms of L. chuanxiong extraction on oxidative stress induced by myocardial ischemia injury in rats. The rats were subcutaneously injected with isoprenaline hydrochloride to induce myocardial ischemia injury and treated for 2 weeks. Then the cardiac indexes of the rats were recorded. The concentration of malondialdehyde (MDA) and activities of serum creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were measured by colorimetry. Light microscope was used to observe the morphological changes of myocardium, and the protein expressions of nuclear factor E2 related factor 2 (Nrf2), quinone oxidoreductase (NQO1) and hemeoxygenase-1 (HO-1) in cardiac tissue were evaluated by Western blot. The results showed that L. chuanxiong extraction could decrease cardiac indexes and the values of CK, LDH and AST in blood serum, increase activities of serum SOD and T-AOC, reduce serum MDA concentration, improve myocardium structure after ischemia injury, and up-regulate the protein expressions of Nrf2, NQO1 and HO-1 in cardiac tissue. These findings revealed that the cardioprotective effects of L. chuanxiong extraction may be related to inhibiting oxidative stress through the activation of Nrf2 signaling pathway.

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/d-α-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment.

Oleanolic acid (OA) is a triterpenoid found in various fruits and vegetables and used in traditional Chinese medicine. OA plays a crucial role in the treatment of several cancers, but poor water solubility, low permeability, and significant efflux have limited its widespread clinical use. Vitamin E-d-α-tocopheryl polyethylene glycol succinate (vitamin E-TPGS) and Pluronic P105 were used to improve the solubility and permeability and to decrease the efflux of OA. OA-loaded mixed micelles were prepared by ethanol thin-film hydration. The physicochemical properties of the micelles, including zeta potential, morphology, particle size, solubility, drug loading, and drug entrapment efficiency were characterized. OA release from micelles was slower than that from the free drug system. OA uptake by A549 non-small-cell lung cancer (NSCLC) cells was enhanced by the micelles. A tumor model was established by injecting A549 cells into nude mice. In vivo imaging showed that OA-micelles could accumulate in the tumors of nude mice. Additionally, smaller tumor size and increased expression of pro-apoptotic proteins were observed in OA-micelle-treated mice, indicating that OA-micelles are more effective than free OA in treating cancer. In vitro experiments were performed using two NSCLC cell lines (A549 and PC-9). Cytotoxicity evaluations showed that the half-maximal inhibitory concentrations of free OA and OA-micelles were 36.8±4.8 and 20.9±3.7 µM, respectively, in A549 cells and 82.7±7.8 and 56.7±4.7 µM, respectively, in PC-9 cells. Apoptosis assays revealed that the apoptotic rate of OA-micelle-treated A549 and PC-9 cells was higher than that of cells treated with the same concentration of free OA. Wound healing and transwell assays showed that migration and invasion were significantly suppressed in OA-micelle-treated cells. Immunofluorescence and Western blot analyses confirmed that the epithelial-mesenchymal transition was reversed in OA-micelle-treated cells. Mixed micelles are a promising nano-drug delivery system for lung cancer treatment.

Design and optimization of self-nanoemulsifying drug delivery systems for improved bioavailability of cyclovirobuxine D.

BACKGROUND: The main purpose of this research was to design a self-nanoemulsifying drug delivery system (SNEDDS) for improving the bioavailability of cyclovirobuxine D as a poorly water-soluble drug. MATERIALS AND METHODS: Solubility trials, emulsifying studies, and pseudo-ternary phase diagrams were used to screen the SNEDDS formulations. The optimized drug-loaded SNEDDS was prepared at a mass ratio of 3:24:38:38 for cyclovirobuxine D, oleic acid, Solutol SH15, and propylene glycol, respectively. The optimized formulation was characterized in terms of physicochemical and pharmacokinetic parameters compared with marketed cyclovirobuxine D tablets. RESULTS: The optimized cyclovirobuxine-D-loaded SNEDDS was spontaneously dispersed to form a nanoemulsion with a globule size of 64.80±3.58 nm, which exhibited significant improvement of drug solubility, rapid absorption rate, and enhanced area under the curve, together with increased permeation and decreased efflux. Fortunately, there was a nonsignificant cytotoxic effect toward Caco-2 cells. The relative bioavailability of SNEDDS was 200.22% in comparison with market tablets, in rabbits. CONCLUSION: SNEDDS could be a potential candidate for an oral dosage form of cyclovirobuxine D with improved bioavailability.

[Development ideas of fine pharmaceutical materials of traditional Chinese medicine preparations based on active cluster theory].

The pharmaceutical materials are divided into coarse and fine types in the development of traditional Chinese medicine preparations. Fine materials with clear composition, stable content and high quality control conform to the international development trend of traditional Chinese medicine preparations. In this paper, the status of fine materials was analyzed, and the development ideas were tentatively put forward. On the one hand, the study on simple methods and efficient equipment shall be strengthened for the simultaneous separation of multiple components of traditional Chinese medicine; on the other hand, the knowledge for traditional Chinese medicine shall be broadened to further develop the scientific compatibility of monomers under the guidance of the theory of traditional Chinese medicine.