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In this study, a novel hydrogel system incorporating an amino acid-based deep eutectic solvent (DES) was prepared, and the skin-permeation enhancement of traditional Chinese herb medicine was evaluated using "sanwujiaowan" extract as the model formula. Briefly, a DES-extract complex was constructed by co-heating the herb formula extracts with the amino acid as the hydrogen receptor and citric acid as the hydrogen donor. The DES-extract complex demonstrated excellent dissolution and skin permeability of the complicated ingredients in the extracts. Consequently, the DES-extract complex was introduced to a hydrogel system, which showed better mechanical properties and viscoelasticity performance. Using a collagen-induced arthritis rat model, the DES-hydrogels exerted an enhanced therapeutic effect that significantly reduced the inflammatory response with systemic toxicity of the extracts. Therefore, our work suggests a novel strategy for synergistic transdermal delivery of Chinese herb medicine and local treatments for rheumatoid arthritis.

In the current times, achieving specific targeted and controllable drug delivery remains one of the major challenges in the treatment of hepatocellular carcinoma (HCC). The present study reported the development of a multiple functional indocyanine green (ICG)-cyclodextrin (CD) system, wherein loaded etoposide (EPS) was used as the model chemotherapeutic drug. In the developed system, ICG segment served as a photosensitizer for photothermal therapy (PTT) and the targeting moiety, which was primarily attributed to the specific retention properties in HCC tissues. The Ex vivo evaluation showed that ICG-CD@EPS exhibited a laser-triggered release profile with the photothermal efficiency and cytotoxicity towards HepG2 cells. In vivo evaluation suggested that ICG could navigate the systems to HCC tissues and retained at the site for 48 h, producing a drug accumulation in HCC. Further, laser irradiation boosted EPS release and local hyperthermia effects in HCC. Thus, the present study explored a novel and specific HCC targeting mechanism, and provided a feasible and controllable strategy for synergistic PTT and chemotherapy treatments for HCC.

The freeze-drying process of Angelica sinensis (Oliv.) Diels was studied and evaluated. Using a single factor investigation, drying temperature and pressure were determined as the main factors affecting the drying process. The central composite design (CCD) combined with response surface method was employed to optimize the drying process. Optimal conditions were determined to be 52 Pa, 63 °C, and a slice thickness of 5 mm. Subsequently, samples were compared in terms of chemical constituents, microstructure, and in vitro absorption profiles under different drying operations. The freeze-drying process was effective for the preservation of ferulic acid (1.82 mg/g), Z-ligustilide (13.91 mg/g), and other compositions. The porous and loose characteristic structure enabled rapid release of ferulic acid (71%, 60 min) and Z-ligustilide (32%, 60 min). Therefore, the freeze-drying method is a reasonable and efficient drying method for the dehydration of A. sinensis.

Transdermal delivery of solid nanoparticles remains a big problem. Microneedle administration and subcutaneous injection are the only two feasible approaches. Here, we developed a noninvasive strategy for the transdermal delivery of mesoporous silica nanoparticles (MSNs) using deep eutectic solvent (DES) from amino acid (AA) and citric acid (CA), which showed a substantial enhancement in skin penetration ability. MSNs were surface modified by CA and then reacted with Lysine (Lys) to form the DES-MSNs system. The covalent linkage of MSNs to the surrounding DES immobilized the nanoparticles and provided strong interactions. We used intradermal and transdermal penetration assays to identify that the AACA DES could synchronously drive the MSNs to penetrate across the entire skin via a "Drag" effect. Furthermore, this is the first study to detect the nanoparticles in the blood by topical administration routes. Thus, we achieved the transdermal delivery of the MSNs into blood circulation. This work would extend the application of the MSNs drug carrier system and provide a novel strategy for the controlled and sustained delivery of nanoparticles.

Panax notoginseng (Burk.) F. H. Chen is a Chinese medicinal plant of the Araliaceae family used for the treatment of cardiovascular and cerebrovascular diseases in Asia. P. notoginseng is vulnerable to root rot disease, which reduces the yield of P. notoginseng. In this study, we analyzed the rhizosphere soil and root endophyte microbial communities of P. notoginseng from different geographical locations using high-throughput sequencing. Our results revealed that the P. notoginseng rhizosphere soil microbial community was more diverse than the root endophyte community. Rhodopseudomonas, Actinoplanes, Burkholderia, and Variovorax paradoxus can help P. notoginseng resist the invasion of root rot disease. Ilyonectria mors-panacis, Pseudomonas fluorescens, and Pseudopyrenochaeta lycopersici are pathogenic bacteria of P. notoginseng. The upregulation of amino acid transport and metabolism in the soil would help to resist pathogens and improve the resistance of P. notoginseng. The ABC transporter and gene modulating resistance genes can improve the disease resistance of P. notoginseng, and the increase in the number of GTs (glycosyltransferases) and GHs (glycoside hydrolases) families may be a molecular manifestation of P. notoginseng root rot. In addition, the complete genomes of two Flavobacteriaceae species and one Bacteroides species were obtained. This study demonstrated the microbial and functional diversity in the rhizosphere and root microbial community of P. notoginseng and provided useful information for a better understanding of the microbial community in P. notoginseng root rot. Our results provide insights into the molecular mechanism underlying P. notoginseng root rot and other plant rhizosphere microbial communities.

Ship ballast water contains high concentration of plankton, bacteria, and other microorganisms. If the huge amount of ballast water is discharged without being inactivated, it will definitely spell disaster to the marine environment. Microalgae is the most common species exiting in ballast water, so the detection of the concentration and viability of microalgae is a very important issue. The traditional methods of detecting microalgae in ballast water were costly and need the help of bulky equipment. Herein, a novel method based on microalgae cell intracellular chlorophyll fluorescence (CF) imaging combines with cell bright field (BF) microscopy was proposed. The geometric features of microalgae cells were obtained by BF image, and the cell viability was obtained by CF image. The two images were fused through the classic image registration algorithm to achieve simultaneous detection of the viability and concentration of microalgae cells. Furthermore, a low-cost, miniaturized CF/BF microscopy imaging prototype system based on the above principles was designed. In order to verify the effectiveness of the proposed method, four typical microalgae in ballast water (Platymonas, Pyramimonas sp., Chrysophyta, and Prorocentrum lima) were selected as the samples. The experimental results show that the self-developed prototype can quickly and accurately determine the concentration and the viability of microalgae cells in ship ballast water based on the dual images of BF and CF, and the detection accuracy is equivalent to that of commercial microscope. It was the first time to simultaneously detect the viability and concentration of microalgae cells in ship ballast water using the method that combining the fluorescence and bright field images, moreover, a miniaturized microscopic imaging prototype was developed. Those findings expected to contribute to the microalgae detection and ship ballast water management.

Here, we fabricated amphiphilic polysaccharide micelles for synergistic cancer immunotherapy targeting tumor-associated macrophages (TAMs). Lepidium meyenii Walp. (maca) polysaccharide (MP), a naturally derived macromolecule with a strong TAM-remodeling effect, was grafted on a hydrophobic poly(lactic-co-glycolic acid) (PLGA) segment, with a disulfide bond for redox-sensitive linkage. The amphiphilic polysaccharide derivatives could self-assemble into core (PLGA)-shell (MP)-structured micelles and encapsulate chloroquine (CQ) into the hydrophobic core. By using a 4T1-M2 macrophage co-culture model and a 4T1 tumor xenograft mouse model, we showed that the prepared micelles could co-deliver MP and CQ to the tumor sites and selectively accumulate at TAMs because of the specific properties of MP. Furthermore, the nanoparticles exerted synergistic tumor immunotherapeutic and antimetastatic effects, which might be attributable to the enhanced cell internalization of the micelles and the multiple regulatory mechanisms of MP and CQ. Thus, immunomodulatory MP may be a promising biomaterial for cancer immunotherapy.

To identify bioactive components of Panax notoginseng (PN) roots in raw and steamed forms, chemometrics analyses including bivariate correlation analysis and partial least squares regression were used to establish the relationships between the chromatograms and anti-inflammatory effect of PN samples. The chemical fingerprints of PN were obtained by high performance liquid chromatography. The anti-inflammatory activity was evaluated by the TNF-α and IL-6 inhibiting test. According to the results, raw PN (RPN) displayed a stronger anti-inflammatory effect compared with steamed PN (SPN) samples. Chemometrics analyses showed that notoginsenoside R1, ginsenosides Rg1, Re and Rb1 were the major anti-inflammatory components of RPN, whereas ginsenosides 20(S)-Rg3 was the active one of SPN treating inflammation. The pharmacologic verification was consistent with the predicted results. In addition, the contents of anti-inflammatory components in RPN were higher than those in SPN, which might be the reason that RPN exhibited stronger effect on the inflammation induced by lipopolysaccharide in RAW264.7 cells. These findings could be beneficial for choosing differential markers for the quality control of RPN and SPN.

This work explored the feasibility of using biological polysaccharide to fabricate dissolvable microneedles (MNs) for the purpose of transdermal drug delivery and skin dendritic cell (DC) activation. Panax notoginseng polysaccharide (PNPS), a naturally derived immunoactive macromolecule, was used to fabricate dissolvable MNs. The prepared PNPS MNs showed a satisfactory mechanical strength and a skin penetration depth. By Franz diffusion cell assay, the PNPS MNs demonstrated a high transdermal delivery amount of model drugs. Furthermore, with the assistance of MNs, PNPS easily penetrated across the stratum corneum and target ear skin DCs, activating the maturation and migration of immunocytes by increasing the expressions of CD40, CD80, CD86, and MHC II of skin DCs. Consequently, the matured DCs migrated to the auricular draining lymph nodes and increased the proportions of CD4+ T and CD8+ T cells. Thus, PNPS might be a promising biomaterial for transdermal drug delivery, with adjuvant potential.

In the current study, we developed a synergistic chemo-immunotherapy using doxorubicin (Dox) and a natural polysaccharide as immunomodulator. First, we isolated a polysaccharide (MPW) from the root of Lepidium meyenii Walp. (maca) and characterized its chemical properties. MPW contains → 4) -α-D-Glcp- (1 → glycosidic bonds, while the terminal α-D-Glcp- (1 → group is connected to the main chain through an O-6 bond. This polysaccharide was then modified by cationization (C-MPW) to enhance immunoregulatory activity. MPW and C-MPW were combined with Dox and their chemo-immunotherapy effects on 4T1 tumor-bearing mice were assessed. Results indicated that the combination of MPW/C-MPW exerted a stronger anti-tumor effect than Dox alone, while reducing systemic toxicity and inhibiting tumor metastasis. In addition, MPW and C-MPW exerted tumor immunotherapy effects through the NF-κB, STAT1, and STAT3 signaling pathways, redirecting TAMs to the M1 phenotype that facilitates immunological responses against tumors. As a result, the immunosuppressive tumor microenvironment was remodeled into an immune-activated state due to enhanced secretion of IL-12, TNF-α, and INF-γ. Moreover, C-MPW exerted a stronger immunomodulatory effect than MPW. In conclusion, MPW and its cationic derivative are promising tools for cancer immunotherapy.

This study isolated and characterized a novel polysaccharide (PNPS-0.3) from the residue of Panax notoginseng by gradient elution. PNPS-0.3 mainly consisted of a backbone of →4)- α-D-GalAp-(1 → 4-β-L-Rhap-1 → 4)-β-D-Galp-(1 → residues, with an α-L-Araf-1 → 5)-α-L-Araf-(1 → branch connecting to the backbone at O-3 of →4-β-L-Rhap-1 → and a molecular weight of 76,655 Da. Furthermore, the adjuvant potential of PNPS-0.3 with bone marrow dendritic cells (BMDCs) was investigated. The results suggested that PNPS-0.3 could induce maturation of BMDCs by reshaping the morphology, upregulating the CD40, CD80, CD86 and MHC II membrane phenotypic markers, and by promoting the secretion of TNF-α and IL-12 proinflammatory cytokines. Moreover, PNPS-0.3 can trigger the DC-induced T-cell immune response, as indicated by the higher expressions of CD4, CD8, CD69, and MHC II in T cells with increased secretion of INF-β. Furthermore, PNPS-0.3 can bind to the pattern recognition receptors (PRR) of Toll-like receptor 4 (TLR 4), Toll-like receptor 2 (TLR 2), and mannose receptor (MR) on BMDCs. PNPS-0.3 also upregulated the expressions of Myd88, IKKβ, PP65, T-P65, and NF-κB, suggesting that the TLR4/TLR2-NF-κB signaling pathway was involved in the immunomodulatory mechanism. In conclusion, the immunoadjuvant potential of novel PNPS-0.3 was characterized, which is beneficial for the future utilization and development of P. notoginseng.

In this investigation, innovative pH-sensitive and amphiphilic nanoparticles (NPs) were synthesized by grafting histidine (His, pH sensitive molecule) and stearic acid (SA, hydrophobic segment) onto the polysaccharides of Bletilla striata (BSP). The His-SA-BSP was able to self-assemble into NPs with pH sensitivity. The acidic conditions could trigger the imidazole ionization and reverse the surface charge, while the electrostatic repulsion wrecked the structure and drove the NPs to a swollen state, as revealed by dynamic light scattering (DLS), transmission electron microscopy (TEM), and critical micelle concentration (CMC) analyses. By increasing the degree of substitution (DS) of His, the NPs showed improved pH sensitivity. The NPs could accelerate Doxorubicin (Dox) release to a remarkably greater extent (3-fold) at pH 5 than at pH 7.4. The CCK-8 assay demonstrated a good biocompatibility of the NPs towards different cell lines and a specific inhibition effect of Dox-loaded NPs against tumor cells. Furthermore, the NPs showed the improved cellular uptake of Dox towards MCF-7 by fluorescence microscopy and flow cytometry. Therefore, the new His-SA-BSP showed potential applications in drug nanocarrier systems.

A microwave processing technology was applied to degrade saponins from the stems and leaves of Panax notoginseng. Six transformation products (1–6), named 20(S)-ginsenoside Rg3 (1), 20(R)-ginsenoside Rg3 (2), notoginsenoside SFt3 (3), ginsenoside Rk1 (4), ginsenoside Rg5 (5), and 20(S)-ginsenoside Rh2 (6) were isolated and identified from a microwave processed extract of the stems and leaves of P. notoginseng (MEL). This transformation method was also applied for producing the minor ginsenosides in flowers, seeds and pedicels of P. notoginseng. The extract and compounds 1–6 in MEL were evaluated in vitro for anticancer and anticoagulant activities. The results showed that the MEL extract and transformation products had outstanding inhibitory activities against human cervical cancer Hela and lung cancer A549 cells. The strongest inhibitory effect was observed for 20(S)-Rh2 (6) with an IC50 value of 8.23 μM in Hela cells. Moreover, the results showed that the MEL significantly prolonged prothrombin time in a concentration-dependent manner. The anticoagulant effect of the MEL improved with the increased contents of Rk1, Rg5, and SFt3.

An isobaric tags for relative and absolute quantitative (iTRAQ)-based quantitative proteomic approach was used to screen the differentially expressed proteins during control treatment (CK), aluminum (Al) and Al+ indole-3-acetic acid (IAA) treatment of wheat lines ET8 (Al-tolerant). Further, the the expression levels of auxin response factor (ARF), Aux/IAA, Mitogen activated protein kinase (MAPK) 2c, and MAPK1a were analyzed. Results showed that 16 proteins were determined to be differentially expressed in response to Al and IAA co-treatment compared with Al alone. Among them, MAPK2c and MAPK1a proteins displayed markedly differential expression during the processes. The expression of ARF2 was upregulated and Aux/IAA was downregulated by Al, while both in concentration- and time-dependent manners. Western-blot detection of MAPK2c and MAPK1a indicated that Al upregulated MAPK2c and downregulated MAPK1a in both concentration- and time-dependent manners. Exogenous IAA could promote the expression of MAPK2c, but inhibit the expression of MAPK1a in the presence/absence of Al. These findings indicated that IAA acted as one of the key signaling molecule controls the response mechanism of wheat malic acid efflux to Al stress through the suppression/activation of Aux/IAA and ARFs, and the activity of MAPK2c and MAPK1a were positively or negatively regulated.

This study developed novel ionic liquids (ILs) based on amino acids. We first screened 15 methyl amino acid ester hydrochlorides ([AAC1]Cl) for their skin permeation enhancements using 5-Fluorouracil (5-Fu) and Hydrocortisone (HC) as model drugs. Glycine methyl ester hydrochloride ([GlyC1]Cl), L-proline methyl ester hydrochloride ([L-ProC1]Cl), and L-leucine methyl ester hydrochloride ([L-LeuC1]Cl) were selected, and their ester sites were modified with different carbon chains (C8 and C12). The resulting ILs showed improved permeation to the two drugs. TEWL and CLSM assays revealed the moderation effects of the modified ILs on skin barrier function, whereas L-proline dodecyl ester hydrochloride ([ProC12]Cl) and L-leucine dodecyl ester hydrochloride ([L-LeuC12]Cl) exhibited the strongest activities. Permeation mechanisms were further investigated by ATR-FTIR, solid-NMR, SEM, and TEM analyses. The results suggested that [L-ProC12]Cl and [L-LeuC12]Cl combined the advantages of amino acid esters and IL solvent and could interact with the intercellular lipid domain by the multi-functions of lipid fluidization and lipid extraction, which were observed in a dosage- and time-dependent manner. Additionally, pathological examination suggested that the amino acid ester-based ILs (AAE-ILs) had good biocompatibility. In conclusion, this study has generated novel chemical penetration enhancers (CPEs) based on AAE-ILs and may be potentially utilized in drug transdermal delivery systems (TDDSs).

Panax notoginseng (Burk.) F. H. Chen is a medicinal herb used to treat blood disorders since ancient times, of which the steamed form exhibits the anti-anemia effect and acts with a “blood-tonifying” function according to traditional use. The present study aimed to investigate the anti-anemia effect and underlying mechanism of steamed P. notoginseng (SPN) on mice with blood deficiency syndrome induced by chemotherapy. Blood deficiency syndrome was induced in mice by cyclophosphamide and acetylphenylhydrazine. A number of peripheral blood cells and organs (liver, kidney, and spleen) coefficients were measured. The mRNA expression of hematopoietic function-related cytokines in the bone marrow of mice was detected by RT-qPCR. The janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway was screened based on our previous analysis by network pharmacology. The expression of related proteins and cell cycle factors predicted in the pathway was determined by Western blot and RT-qPCR. SPN could significantly increase the numbers of peripheral blood cells and reverse the enlargement of spleen in a dose-dependent manner. The quantities of related hematopoietic factors in bone marrow were also increased significantly after SPN administration. SPN was involved in the cell cycle reaction and activation of immune cells through the JAK-STAT pathway, which could promote the hematopoiesis.

This study presented the first purification and characterization of a hepatoprotective polysaccharide (PNPS-0.5 M) from the residue of Panax notoginseng (Burk.) F.H. Chen. This polysaccharide included a backbone of (4 → 1)-linked GalA and branches of (1→)-linked Araf, (1→)-linked Rhap, and (5 → 1)-linked Araf and had an extremely high molecular weight (2600 kDa). We investigated the hepatoprotective effects of PNPS-0.5 M on mice with alcoholic liver damage (ALD). After administration of PNPS-0.5 M, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and hepatic malondialdehyde (MDA) were reduced to normal. In contrast, hepatic levels of alcohol dehydrogenase (ADH) and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were elevated to normal. Further investigations indicated that PNPS-0.5 M activated Nrf2 signaling as a protective mechanism against Cyp2e1 toxicity in ALD mice. Meanwhile, it strengthened the ADH pathway and suppressed the CAT pathway of alcohol metabolism to prevent peroxide accumulation, thereby ameliorating ALD. In the present study, we describe a novel acidic polysaccharide from P. notoginseng with hepatoprotective activity that facilitates the development and utilization of P. notoginseng resources.

To identify bioactive components of

In this work, imidazolium ionic liquids (imidazolium ILs) were employed as the novel chemical permeation enhancers (CPEs) and their performances and mechanisms of action were deeply investigated. Testosterone was used as a model drug to investigate the transdermal delivery enhancement of twenty imdidazolium ILs. The results suggested that the promotion activity connected to the structure and composition of the ILs. The quantitative structure-activity relationship (QSAR) model revealed a good linearity between the electronic properties of ILs and their enhancements. Furthermore, the transepidermal water loss (TEWL) and scanning laser confocal microscope (CLSM) examinations showed the strong improvement of ILs on skin barrier permeability, which were well correlated with the drug penetration profiles. The total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscope (AFM) evaluations of skins indicated that the ILs can disrupt the regular and compact arrangements of the corneocytes, change the surface properties of stratum corneum, and make the skin structure more permeable. Our work demonstrated the significant skin permeation promotion profiles of the imidazolium ILs, which are of great potential in transdermal drug delivery systems.

The Panax notoginseng (P. notoginseng) stem leaf is rich in flavonoids. However, because of a lack of research on the flavonoid extraction process and functional development of P. notoginseng stem leaf, these parts are discarded as agricultural wastes. Therefore, in this study, we intend to optimize the extraction process and develop the skin-whitening functions of P. notoginseng stem leaf extracts. The extraction process of the stem and leaf of P. notoginseng flavonoid (SLPF) is optimized based on the Box&ndash, Behnken design (BBD) and the response surface methodology (RSM). The optimum extraction conditions of the SLPF are as follows: the extraction time, the ethanol concentration, the sodium dodecyl sulfate (SDS) content and the liquid material ratio (v/w, which are 52 min, 48.7%, 1.9%, and 20:1, respectively. Under the optimal extraction conditions, the average total SLPF content is 2.10%. The antioxidant activity and anti-deposition of melanin of mouse B16 cells of P. notoginseng stem leaf extracts are studied. The results indicate that the EC50 values of reducing activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activities, the superoxide anion removal ability, and the 2,2-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) free radical removal ability are 7.212, 2.893, 2.949, and 0.855 mg/mL, respectively. The extracts IC50 values of the tyrosinase and melanin synthesis are 0.045 and 0.046 mg/mL, respectively. Therefore, the optimal processing technology for the SLPF obtained in this study not only increases its utilization rate, but also decreases material costs. The extracts from the P. notoginseng stem leaf may be developed as food or beauty products.

In this investigation, innovative pH-sensitive and amphiphilic nanoparticles (NPs) were synthesized by grafting histidine (His, pH sensitive molecule) and stearic acid (SA, hydrophobic segment) onto the polysaccharides of

The present study aims to optimize the ethanol-reflux extraction conditions for extracting saponins from steamed Panax notoginseng (SPN). Four variables including the extraction time (0.5–2.5 h), ethanol concentration (50–90%), water to solid ratio (W/S, 8–16), and times of extraction (1–5) were investigated by using the Box-Behnken design response surface methodology (BBD-RSM). For each response, a second-order polynomial model with high R2 values (>0.9690) was developed using multiple linear regression analysis and the optimum conditions to maximize the yield (31.96%), content (70.49 mg/g), and antioxidant activity (EC50 value of 0.0421 mg/mL) for saponins extracted from SPN were obtained with a extraction time of 1.51 h, ethanol concentration of 60%, extraction done 3 times, and a W/S of 10. The experimental values were in good consistency with the predicted ones. In addition, the extracted SPN saponins could significantly increase the levels of blood routine parameters compared with the model group (p < 0.01) and there was no significant difference in the hematopoiesis effect between the SPN group and the SPN saponins group, of which the dose was 15 times lower than the former one. It is suggested that the SPN saponins extracted by the optimized method had similar functions of “blood tonifying” at a much lower dose.

A novel microemulsion was developed and characterized for topical delivery of Dencichine (Den). Two imidazaolium ionic liquid, 1-hydroxyethyl-3-methylimidazolium chloride ([HOEIM]Cl) and 1-butyl-3-methylimidazolium dodecanesulfate ([BMIM]C12SO3) were incorporated into the aqueous and surfactant phases respectively for the remarkable enhancement on skin permeation. The nano-carrier was developed and optimized based on a pseudo-ternary phase diagram. The optimized formulation was composed of 50% water/[HOEIM]Cl mix (1:1) as water phase, 20% Tween 80/[BMIM]C12SO3 mix (1:1) as surfactant, 10% propylene glycol as co-surfactant and 20% IPM as oil phase. The o/w microemulsion was then characterized for droplets sizes (47.7±1.5nm), zeta potential (-14.83±3.64mV), viscosity (31±4 mPa) and pH (6.71±0.04). In-vitro skin permeation assay suggested the strong enhancement of ILs formulation on the topical delivery of Den, which was approximately 10-fold that of the drug aqueous solution. It was found that the nano-carrier can reduce the skin barrier properties by disrupting the regular and compact arrangements of corneocytes, and moderating the surface properties of the stratum corneum, as evidenced by Transdermal Water Loss Evaluation (TEWL), Differential Scanning Calorimetery (DSC) and attenuated total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR). Furthermore, the in-vivo pharmacodynamic evaluation indicated the significant hemostatic activity of Den by the topical application of the vehicle. Additionally, the formulation showed minor cell toxicity and skin irritation. Therefore, our work suggested that the ionic liquid microemulsion can be a promising nano-scale vehicle for the topical application of Den to produce desirable pharmacological effects.

Natural polysaccharides constitute promising material for nano-drug delivery systems (NDDS) due to their excellent biodegradability and biocompatibility. Previously, novel copolymer micelles (His-SA-BSP) were successfully engineered based on the functionalization of Bletilla striata polysaccharides (BSP) by histidine (His) and stearic acid (SA). In this work, the effectiveness of the designed micelles in selectively delivering Doxorubicin (Dox) to tumor cells is evaluated. The obtained results show satisfactory encapsulation efficiency, loading capacity, and drug compatibility of the copolymers. Surface charge conversion and micelle deterioration were observed at pH = 6.5 and pH = 5.0, respectively. In vitro Dox release assays indicate a rapid release of Dox from micelles under acidic conditions of tumor microenvironments. Furthermore, in vitro cytotoxicity and cellular uptake assays performed on Michigan Cancer Foundation-7 (MCF-7) cells suggest that the proposed micelles are safe to use in biological systems, and that they can be easily and selectively accumulated at the tumor site due to pH sensitivity. Endocytosis inhibition and intracellular delivery assays reveal that BSP nanocarriers are mainly delivered to lysosomes by micropinocytosis. The acidic condition of lysosomes (pH = 5.0) then triggers the disintegration micelles, resulting in a fast release of Dox to the nuclei. Finally, in vivo biodistribution and antitumor assessments conducted on MCF-7-BALB/c tumor xenograft mice confirm the enhanced tumor accumulation and antitumor efficacies of the investigated Dox-loaded micelles. In conclusion, the pH-sensitive drug delivery systems designed previously are shown to yield improved accumulation of the drug at the tumor site, enhanced intracellular uptake, and efficient in vivo antitumor efficacy.

Effect of different water conditions on the physiological indexes (e.g.seed water content, vigor, antioxidase activities)of Panax notoginseng seeds were studied under process of after-ripening and germination.The results showed show that compared with 2.5% treatment, under the treatment of 5%, P.notoginseng seeds possessed stable seed water content, the seed vigor was exceed by 51%,variation of antioxidant enzyme (SOD, POD, CAT) activity and malondialdehyde (MDA) content were small, crude fat and total sugar content decreased significantly.With the increase of PEG 6000 concentration, the germination characteristic indexes obviously decreased, antioxidase activities increased firstly and decreased afterwards, content of MDA, soluble protein and total sugar increased obviously.There were significant positive correlation between germination characteristic indexes and osmotic substance content(r0.900, P0.01), and significant negative correlation with MDA (r0.900, P0.01).In conclusion, because the characteristic of dehydration intolerance of P.notoginseng seeds, 5% water content of sand burying stratification treatment was the best for after-ripening, 15% concentration of PEG 6000 treatment was the highest tolerance limit of germination process.

In this study, the extraction process of Maca polysaccharide (LMP) was deeply studied and its chemo‐protective effects on Cyclophosphamide (Cy)‐induced mice were evaluated. By single factor investigation and response surface methodology optimization, it was found that the liquid‐to‐solid ratio, extraction time, and extraction temperature were the main factors which affected the extraction yield of LMP. The optimum extraction process was obtained by Box–Behnken design combined with response surface methodology. It was found that, at the condition of liquid‐to‐solid ratio of 30:1; extraction time of 2.3 hr; and extraction temperature of 90°C, the yield of the LMP could reach 46.56%. Furthermore, by oral administration of LMP, the cyclophosphamide‐induced mice showed the proliferation of lymphocyte and the phagocytic capacity of macrophages’ enhancements. The number of white blood cell, red blood cell, and platelets in the peripheral blood were up‐regulated; the spleen total superoxide dismutase, Catalase, and Glutathione‐peroxidase activities were enhanced, while the Serum malondialdehyde and Triacylglycerols content was reduced. Therefore, our work provided an effective way for extraction of LMP and demonstrated the chemo‐protective effects of LMP on the animal level. PRACTICAL APPLICATION: Natural polysaccharides from functional food sources are widely accepted for their bioactive activities. As extraction conditions significantly affected the quality and yield of polysaccharides, the effective extraction process for polysaccharides should be systematically investigated. In the current work, the optimum conditions for polysaccharides extraction from Maca (Lepidium meyenii Walp.) (LMP) were obtained using liquid‐to‐solid ratio of 30:1 for 2.3 hr at 90°C. The Mass characterization and Monosaccharide Composition of LMP were also determined. Furthermore, the extracted LMP exhibited well Chemo‐protective activities on Cyclophosphamide‐induced mice. Therefore, our work showed the potential applications of Maca polysaccharides as the easily accessible source of natural immunopotentiating agents in function food and pharmaceutical industry.

Crohn’s disease (CD) is one of the two major types of inflammatory bowel disease (IBD) thought to be caused by genetic and environmental factors. Recently, miR-122 was found to be deregulated in association with CD progression. However, the underlying molecular mechanisms remain unclear. In the present study, the gene nucleotide-binding oligomerization domain 2 (NOD2/CARD15), which is strongly associated with susceptibility to CD, was identified as a functional target of miR-122. MiR-122 inhibited LPS-induced apoptosis by suppressing NOD2 in HT-29 cells. NOD2 interaction with LPS initiates signal transduction mechanisms resulting in the activation of nuclear factor κB (NF-κB) and the stimulation of downstream pro-inflammatory events. The activation of NF-κB was inhibited in LPS-stimulated HT-29 cells pretreated with miR-122 precursor or NOD2 shRNA. The expression of the pro-inflammatory cytokines TNF-α and IFN-γ was significantly decreased, whereas therelease of the anti-inflammatory cytokines IL-4 and IL-10 was increased in LPS-stimulated HT-29 cells pretreated with miR-122 precursor, NOD2 shRNA or the NF-κB inhibitor QNZ. Taken together, these results indicate that miR-122 and its target gene NOD2 may play an important role in the injury of intestinal epithelial cells induced by LPS.

The purpose of the present study was to design and evaluate a monolithic drug-in-adhesive patch with a novel pressure-sensitive adhesive (PSA) matrix based on styrene–isoprene-styrene (SIS) block copolymer. Testosterone was selected as the model drug. The orthogonal array design for ternary mixtures was employed to optimize the amounts of SIS, C-5 hydrocarbon resin, and liquid paraffin. The drug release percentage, water vapor permeability, adhesive properties were chosen as response variables. The patch formulation was optimized by investigating the effects of the drug loading capacity, the type, and amount of permeation enhancer on the adhesive properties and skin permeation. The compositions of the optimal matrix were: 120 g of SIS copolymer, 120 g of C-5 hydrocarbon resin, 60 g of liquid paraffin. An optimized formulation with maximum skin permeation and acceptable adhesive properties was developed incorporating 2% testosterone and 6% isopropyl myristate. No significant differences for in vitro release, skin permeation, and in vivo absorption were observed between the optimal formulation and Testopatch®. The stability evaluation showed that the patches were stable at 25°C/60% relative humidity for 6 months. The result indicated that SIS copolymer was a suitable and compatible polymer for the development of PSA. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2221–2234, 2013

A novel drug-in-adhesive matrix was designed and prepared. A thermoplastic elastomer, styrene–isoprene–styrene (SIS) block copolymer, in combination with tackifying resin and plasticizer, was employed to compose the matrix. Capsaicin was selected as the model drug. The drug percutaneous absorption, adhesion properties, and skin irritation were investigated. The results suggested that the diffusion through SIS matrix was the rate-limiting step of capsaicin percutaneous absorption. [SI] content in SIS and SIS proportions put important effects on drug penetration and adhesion properties. The chemical enhancers had strong interactions with the matrix and gave small effect on enhancement of drug skin permeation. The in vivo absorption of samples showed low drug plasma peaks and a steady and constant plasma level for a long period. These results suggested that the possible side effects of drug were attenuated, and the pharmacological effects were enhanced with an extended therapeutic period after application of SIS matrix. The significant differences in pharmacokinetic parameters produced by different formulations demonstrated the influences of SIS copolymer on drug penetrability. Furthermore, the result of skin toxicity test showed that no skin irritation occurred in guinea pig skin after transdermal administration of formulations.

We prepared pressure-sensitive adhesive (PSA) patches based on styrene–isoprene–styrene (SIS) thermoplastic elastomer using hot-melt coating method. The liquid paraffine is added in the PSA matrices as a plasticizer to moderate the PSA properties. Three drugs, methyl salicylate, capsaicin, and diphenhydramine hydrochloride are selected as model drugs. The Fourier transform infrared spectroscopy, differential scanning calorimetry test, and wide-angle X-ray diffraction test indicate a good compatibility between drugs and matrices. Peppas equation is used to describe drug release profile. Different drug–matrix absorption, as indicative of drug–matrix interaction, accounts for the variation in release profiles of different drugs. Furthermore, atomic force microscopy and rheological studies of the PSA samples are performed to investigate the effect of SIS structure and plasticizer of PSA on drug release behaviors. For methyl salicylate and capsaicin, drug diffusion in the PSA matrices is the main factor controlled by the release kinetic constant k. The high [SI] diblock content and high plasticizer amount in matrix provide the PSA with a homogeneous and soften microstructure, resulting in a high diffusion rate. But for water-soluble drugs such as diphenhydramine hydrochloride, the release rate is governed by water penetration with the competition from diffusion mechanisms.