[Advances in formation and application of self-assembled nanoparticles from traditional Chinese medicine].

Due to the diverse sources and unique structures, the chemical components of Chinese medicinal materials are easy to self-assemble to form nanoparticles. The formation of self-assembled nanoparticles(SAN) can not only affect the absorption and distribution of the effective ingredients in Chinese medicinal materials but also may improve the biological activity of the effective ingredients or their simple mixtures, which is of great significance for revealing the compatibility mechanism of Chinese medicine prescription, developing new Chinese medicine products, and producing new nanomaterials. This paper reviews the formation, isolation, characterization, and application of SAN of Chinese medicines, and discusses the problems and development trends of the relevant research, which can provide reference for the further study and promote the innovation and application of such SAN.

[Effect of self-assembled nanoparticles from Shaoyao Gancao Decoction on release and absorption of main components of Baishao].

To study the effect of self-assembled nanoparticles from Shaoyao Gancao Decoction(SGD-SAN) on the encapsulation, in vitro release and intestinal absorption of the main components of Baishao. Particle size analysis and morphological observation were used to verify the formation of SGD-SAN in the decoction. The entrapment efficiency(EE) of SGD-SAN on the main components of Baishao was determined by ultrafiltration centrifugation. The dialysis bag method was used to study the in vitro release of the main components of Baishao with pH 6.8 phosphate buffer solution as the release media. Single-pass intestinal perfusion study was performed to investigate the effect of SGD-SAN on the absorption of the main components of Baishao. The results showed that there were nanoparticles in the SGD, and the particle sizes and PDI of SGD-SAN were about 200 nm and 0.38, respectively. SGD-SAN was irregularly spherical under transmission electron microscope(TEM). The EEs of albiflorin, paeoniflorin and benzoylpaeoniflorin in SGD-SAN were 33.78%±1.03%,33.61%±0.90%,88.53%±0.58%, respectively. The release characteristics of albiflorin, paeoniflorin and benzoylpaeoniflorin from SGD-SAN showed a slow-release effect on pH 6.8 phosphate buffer solution media. SGD-SAN could significantly enhance the absorption of albiflorin, paeoniflorin and benzoylpaeoniflorin in the ileum. The results of this study indicated that SAN could be formed during the mixed decoction of Baishao and Gancao, and SGD-SAN could encapsulate the components of Baishao, with a certain slow-release effect, and the formation of SAN facilitated the absorption of drugs in the ileum.

Influence of storage conditions on the infestation of Tyrophagus putrescentiae and prevalence of mite hypersensitivity in Taiwan.

Sensitization to mites is a considerable factor in the development of allergic diseases. Because of its abundance, Tyrophagus putrescentiae (Tp) is the predominant storage mite found in home storage rooms, kitchens, and bakeries. Patients allergic to mites might exhibit a severely hypersensitive reaction upon ingesting Tp-contaminated food. The objective of this study was to investigate the rates of Tp contamination in commercial storage products from various areas, storage conditions, and environments in Taiwan. A specific antibody against Tyr p 3, the allergen on Tp, could be used as an indicator to monitor the contamination condition in storage foods. The microscopic mite examination, allergen detection by ELISA and cultured mite chemotaxis were used to evaluate the prevalence of T. putrescentiae contamination. Moreover, the IgE responses of patients allergic to mites were examined. We found that pet food and mushrooms were commonly contaminated with Tp, and this was validated through Tyr p 3 concentration and chemotaxis experiments. Tp contamination rates decreased significantly when samples were sealed and stored at a low temperature (<  4 °C), low relative humidity (RH < 60%), or for longer periods at a low temperature. The results of the clinical study indicated that the mites that elicited major positive IgE responses in allergic subjects were Dermatophagoides pteronyssinus and D. farinae. Thus, people who are sensitized to D. pteronyssinus or D. farinae might be at risk of a second anaphylactic reaction due to cross-reactivity upon ingestion of Tp-contaminated food. Accordingly, Tp contamination can be prevented by keeping food packages sealed and stored at a low temperature. This prevents the severe allergic reaction caused by the inadvertent ingestion of contaminated food-borne Tp.

[Study on preparation of volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills and its protective effect on acute myocardial ischemia injury].

In this study, solid dispersion technology was used to develop volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills(VOA-SNEDDS-DP) and its protective effect on acute myocardial ischemia injury was evaluated. Taking exterior quality, weight variation and the resolving time as comprehendsive evaluation indexes, the preparation process and formulation of the dropping pills were optimized by orthogonal design, and the dissolution rate in vitro of the optimized VOA-SNEDDS-DP was investigated. The rat model of acute myocardial ischemia was induced by intraperitoneal injection of isoproterenol hydrochloride and the serum levels of superoxide dismutase(SOD), malondialdehyde(MDA), creatine kinase(CK) and pathological changes of myocardial tissue were determined to evaluate therapeutic effect of the dropping pills on acute myocardial ischemia. The results showed that the optimal formulation and preparation process of VOA-SNEDDS-DP were as follows: PEG6000-PEG8000 was 1∶1, proportion of VOA-SNEDDS and matrix was l∶2.5, the temperature of drug fluids was 75 ℃, drop rate was 35 drops/min, drop distance was 5 cm, the condensing agent temperature was 2-10 ℃. The content of ß-asarone in the dropping pills was 42.46 mg·g~(-1). The accumulated dissolution rate of the dropping pills reached 93.85% in 10 min. The results of pharmacodynamic experiments showed that VOA-SNEDDS-DP could significantly increase the SOD content(P<0.05), reduce the levels of MDA and CK(P<0.05) in serum, and effectively improve the pathological morphology of myocardial tissue. These results revealed that the preparation of VOA-SNEDDS-DP by solid dispersion technology was stable and feasible, and VOA-SNEDDS-DP had protective effect on acute myocardial ischemia injury.

[Preparation and in vitro anti-hepatic fibrosis evaluation of herpetone nanosuspensions].

Herpetone( HPT) is a bioactive lignan extracted from Herpetospermum pedunculosum,which can protect liver,lower aminotransferase and inhibit hepatitis B virus. However,HPT has a poor oral bioavailability due to its poor water solubility. And there is no report about whether HPT has an anti-hepatic fibrosis activity. To improve the dissolution of HPT and study its anti-hepatic fibrosis activity and mechanism,the study group prepared herpetone nanosuspensions( HPT-NS) by the miniaturized media milling method. The formulation and process of HPT-NS were optimized by the single factor experiment. Scanning electron microscopy was used to observe morphology of HPT-NS. Dialysis method was used to study dissolution of HPT-NS in vitro. CCK8 method was used to assess the effect of HPT-NS on proliferation of the rat hepatic stellate cells( HSC-T6). Flow cytometry was used to assess the effect of HPT-NS on apoptosis and cell cycle of HSC-T6. The mean particle size of optimized HPT-NS was( 196±7) nm with a polydispersity index of 0.279±0.009.SEM showed that HPT-NS was in a regular rod shape. The cumulative dissolution rate of HPT-NS reached 93% in 18 h,and was higher than that of herpetone coarse suspensions( HPT-CS,28%). CCK8 experiment showed that the inhibition rate of HPT-NS on HSC-T6 was higher than that of HPT-CS. Flow cytometry showed that HPT-NS could block HSC-T6 cells in G2/M phase and induce apoptosis of HSC-T6 cells,with a significantly stronger effect than HPT-CS. The results revealed that HPT-NS significantly increased the in vitro dissolution of HPT,and enhanced the inhibitive effect on HSC-T6 cell proliferation by blocking cells in the G2/M phase and inducing late apoptosis.

[Preparation of astilbin amorphous nanosuspension and its in vitro evaluation].

Astilbil nanosuspension (AT-NS) was prepared by an antisolvent precipitation method. The formula and process of AT-NS were optimized by the single factor experiment. AT-NS was prepared under the optimal conditions, and its morphology and crystallinity were characterized. In vitro release of AT-NS was also determined. The particle size of AT-NS stabilized by PVP K30 was (149±3) nm, and the polydispersity index (PDI) and stability index (SI) were 0.137±0.014 and 0.940±0.012, respectively. The results of SEM showed that AT-NS was spherical. Both XRD and DSC showed that AT was amorphous in nanosuspension. In the in vitro release test, AT-NS showed a significantly increased dissolution. This simple low-cost approach could prepare AT-NS successfully. AT-NS could significantly improve the dissolution of AT and provide the reference to break the limitation on the clinical application of AT.

[Research progress on in vitro and in vivo behaviors of poorly soluble Chinese materia medica nanosuspension].

Nanosuspension (also called nanocrystal suspension or nanocrystal) could significantly enhance the saturated solubility and dissolution of insoluble drugs, and improve their bioavailability by reducing particle size and increasing the specific surface, which could then solve the delivery problems of the poorly soluble active ingredients and effective parts of Chinese materia medica (CMM). Based on the brief summaries of nanosuspension preparation methods, this paper would mainly review the in vitro and in vivo behaviors of poorly soluble CMM nanosuspension, discuss and analyze its problems, so as to provide reference and thinking for the further study of nanosuspension drug delivery system of poorly soluble CMM and promote the development and perfection of nanosuspension technology in CMM.

[Preparation and quality evaluation of volatile oil from Acori Tatarinowii Rhizoma self-nanoemulsion].

In order to increase the solubility of volatile oil from Acori Tatarinowii Rhizoma, this study was to prepare self-nanoemulsion of volatile oil from Acori Tatarinowii Rhizoma . The prescriptions were preliminarily screened by miscibility studies, excipient compatibility tests, and pseudo-ternary phase diagrams, and then the optimal formulation was obtained by using the Box-Behnken response surface method, with particle size and drug-loading rate as the indicators. The self-nanoemulsion prepared by optimal prescription was characterized and evaluated for in vitro dissolution. The results showed that the optimal prescription for this volatile oil self-nanoemulsion was as follows: 41.7% volatile oil, 46.8% Tween-80, and 11.5% PEG-400. The prepared self-nanoemulsion was clear and transparent, with drug-loading of (192.77±1.64) mg·g⁻¹, particle diameter of (53.20±0.94) nm, polydispersity index of 0.230± 0.013, and Zeta potential of (-12.2±0.7) mV. The in vitro dissolution of self-nanoemulsion was higher than that of volatile oil. In this research, volatile oil served as the oil phase in self-nanoemulsion, so the prescription was simpler and the drug loading rate was higher. The prepared self-nanoemulsion complied with the relevant quality requirements, providing a reference for the preparation of volatile oil formulations.

[Preparation of isopsoralen loaded nanostructured carrier and its in vitro transdermal permeation characteristics].

To increase the permeation and retention of isopsoralen in skin, and improve its bioavailability.Isopsoralen loaded nanostructure liquid carrier (IPRN-NLC) was prepared by high pressure homogenization andoptimized by orthogonal experiment with the encapsulation efficiency, drug loading and average particle size as the evaluation indexes. The in vitro transdermal permeation of IPRN-NLC was evaluated by Franze diffusion cells.The results showed that solid-liquid lipid ratio of optimum IPRN-NLC formulation was 7∶3,drug-lipid ratio of 1∶30, 1% surfactant. Under these conditions, IPRN-NLC had an average encapsulation of （90.25±0.73）%,drug loading of （1.56±0.27）% and an average particle size of (305±1.57) nm.The in vitro transdermal permeation results showed that IPRN-NLC could increase the amount of IPRN permeated though skin, with 3 times of the epidermal retention as compared with IPRN solution. From the results we can know that the IPRN-NLC prepared by high pressure homogenization can improve the permeation andaccumulation of IPRN in the skin, with wide application prospects in the field of transdermal administration.

[Preparation of nanosuspension of quercetin with a miniaturized milling method].

The nanosuspension of quercetin (QT-NS) was prepared by a miniaturized milling method, and the process was optimized by Box-Behnken response surface method. Then the accumulative release rate of QT-NS in vitro was determined. The results showed that the optimal process parameters were as follows: ZrO2 4.5 mL, milling speed 690 r•min⁻¹ and milling time 1.5 h; the particle size of QT-NS was (169±5) nm, polydispersity index of 0.204±0.006 and stability index of 0.827±0.014, respectively. There was a little deviation between the theoretically predicted value and the measured value, indicating that this model had a good prediction effect. The accumulative release rate in vitro of QT-NS in 120 min was significantly higher than that of the raw drug and physical mixture. This simple low-cost miniaturization approach could prepare QT-NS successfully, and could provide reference for the formulation of the nanosuspension.

[Preparation of tanshinone â ¡A loaded nanostructured lipid carrier and its in vitro transdermal permeation characteristics].

To prepare tanshinone ⅡA loaded nanostructured lipid carrier (Tan ⅡA-NLC), and study its in vitro transdermal permeation characteristics. The Tan ⅡA-NLC was prepared by high pressure homogenization technology and optimized by Box-Behnken design-response surface method, and it was characterized in terms of morphology, particle size, zeta potention, et al. The transdermal permeation of Tan ⅡA-NLC was evaluated by using Franz diffusion cells. The results showed that, the optimal formulation was as follows: drug/lipid materials ratio 88, GMS/MCT ratio 2, emulsifier concentration 1%, average particle size (182±14) nm, polydispersity index PDI (0.190 6±0.024 5), zeta potential (－27.8± 5.4) mV, encapsulation efficiency EE (86.44%±9.26%) and drug loading DL (0.98%±0.18%), respectively. The in vitro transdermal permeation results showed that as compared with Tan ⅡA solution, Tan ⅡA-NLC had lower transdermal permeation amount after applying drug for 24 h, but its retention in the epidermis was 3.18 times that of solution. These results indicated that the prepared Tan ⅡA-NLC could effectively increase the regention of Tan ⅡA in the epidermis, and had a broad application prospect.

[Analysis on intestinal absorption of paeoniflorin lipid liquid crystalline nanoparticles via everted intestinal sacs].

To study the absorption kinetics of paeoniflorin lipid liquid crystalline nanoparticles (Pae-LLCN) in different intestinal segments of rats and compare them with paeoniflorin(Pae) solution. Rat everted gut sac models were adopted for intestinal absorption test, and Pae content was determined by HPLC method to study the absorption characteristics of Pae-LLCN in rat duodenum, jejunum, ileum and colon, and investigate the effects of different drug concentrations on intestinal absorption. Results showed that Pae-LLCN and Pae were well absorbed at different intestine segments and different concentrations. The absorption constant Ka was increased with the increasing of the drug concentration, indicating possible passive absorption. The accumulative absorption volume Q and absorption constant Ka of Pae-LLCN were higher than those of Pae at each intestinal segment(P<0.05). The results revealed that Pae-LLCN and Pae could be well absorbed in whole intestinal segments and its mechanism may be passive absorption. LLCN can effectively improve the intestinal absorption of Pae.

Deregulated microRNAs in triple-negative breast cancer revealed by deep sequencing.

BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNA molecules that play critical roles in human malignancy. However, the regulatory characteristics of miRNAs in triple-negative breast cancer, a phenotype of breast cancer that does not express the genes for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, are still poorly understood. METHODS: In this study, miRNA expression profiles of 24 triple-negative breast cancers and 14 adjacent normal tissues were analyzed using deep sequencing technology. Expression levels of miRNA reads were normalized with the quantile-quantile scaling method. Deregulated miRNAs in triple-negative breast cancer were identified from the sequencing data using the Student's t-test. Quantitative reverse transcription PCR validations were carried out to examine miRNA expression levels. Potential target candidates of a miRNA were predicted using published target prediction algorithms. Luciferase reporter assay experiments were performed to verify a putative miRNA-target relationship. Validated molecular targets of the deregulated miRNAs were retrieved from curated databases and their associations with cancer progression were discussed. RESULTS: A novel 25-miRNA expression signature was found to effectively distinguish triple-negative breast cancers from surrounding normal tissues in a hierarchical clustering analysis. We documented the evidence of seven polycistronic miRNA clusters preferentially harboring deregulated miRNAs in triple-negative breast cancer. Two of these miRNA clusters (miR-143-145 at 5q32 and miR-497-195 at 17p13.1) were markedly down-regulated in triple-negative breast cancer, while the other five miRNA clusters (miR-17-92 at 13q31.3, miR-183-182 at 7q32.2, miR-200-429 at 1p36.33, miR-301b-130b at 22q11.21, and miR-532-502 at Xp11.23) were up-regulated in triple-negative breast cancer. Moreover, miR-130b-5p from the miR-301b-130b cluster was shown to directly repress the cyclin G2 (CCNG2) gene, a crucial cell cycle regulator, in triple-negative breast cancer cells. Luciferase reporter assays showed that miR-130b-5p-mediated repression of CCNG2 was dependent on the sequence of the 3'-untranslated region. The findings described in this study implicate a miR-130b-5p-CCNG2 axis that may be involved in the malignant progression of triple-negative breast cancer. CONCLUSIONS: Our work delivers a clear picture of the global miRNA regulatory characteristics in triple-negative breast cancer and extends the current knowledge of microRNA regulatory network.

Influence of drug physicochemical characteristics on in vitro transdermal absorption of hydrophobic drug nanosuspensions.

The purpose of this paper was to study the influence of drug physicochemical characteristics on in vitro transdermal absorption of hydrophobic drug nanosuspensions. Four drug nanosuspensions were produced by high-pressure homogenization technique, which were the same in stabilizer and similar in particle size. Differential scanning calorimetry and powder X-ray diffraction analysis showed that the crystalline state of the nanocrystals did not change. In vitro permeation study demonstrated that the drug nanosuspensions have a higher rate of permeation that ranged from 1.69- to 3.74-fold compared to drug microsuspensions. Correlation analysis between drug physicochemical properties and Jss revealed that log P and pKa were factors that influenced the in vitro transdermal absorption of hydrophobic drug nanosuspensions, and drugs with a log P value around 3 and a higher pKa value (when pKa < pH+2) would gain higher Jss in this paper.

[In vitro dissolution rate of Liuwei Wuling tablet based on biological potency and integrated dissolution].

To explore the feasibility of chemical and biological method in evaluation of the in vitro dissolution rate of Liuwei Wuling tablet (LWT), this experiment investigated the inhibitory effect of LWT dissolving solutions on LX-2 hepatic stellate cells in 0.1% SDS dissolution medium in different dissolving periods. From these results, the cumulative dissolution rate of LWT was obtained based on the cell inhibitory rate. The dissolution rates of deoxyschizandrin, phillyrin, and Specnuezhenide were determined by HPLC method. A novel approach of self-defined weighting coefficient had been created to establish the integrated dissolution rate model. Then f2 similar factor method was used to evaluate the relevance of these two methods. The results showed that f2 values for deoxyschizandrin, phillyrin, Specnuezhenide, and the integrated dissolution were 61, 43, 61 and 75 respectively, indicating that the dissolution of multi-component integration could fully reflect the biological potency of the whole recipe. The dissolution evaluation method for multicomponent integration based on biological activity is expected to be one of the effective means for in vitro dissolution test of LWT.

[Influence of stir-baked with sand on active ingredients, diarrhea and hepatoprotection of Herpetospermum caudigerum].

To study the influence of stir-baked with sand on active ingredients, diarrhea and hepatoprotection of Herpetospermum caudigerum, the contents of herperione and herpetin in H. caudigerum before and after stir-baking with sand were analyzed by HPLC. The effect of stir-baked with sand on diarrhea of H. caudigerum TL was evaluated using the mean stool rate (MSR) and mean diarrheal index ( MDI) and the influence of stir-baked with sand on hepatoprotective effect of H. caudigerum TL was examined using a mouse model of CCl4-induced liver injury based on the analysis of serum ALT and AST activities. The results of HPLC analysis showed the content of herperione in H. caudigerum after stir-baking with sand decreased by 40.9% (P < 0.01) and the content of herpetin had no change. Pharmacodynamic results showed that the MSR and MDI of high-dose and middle-dose group of H. caudigerum TL after stir-baking with sand were significantly lower than that of high-dose and middle-dose group of H. caudigerum TL without stir-baking with sand; The high-dose and middle-dose of H. caudigerum TL with/without stir-baking with sand significantly alleviated liver injury as indicated by the decreased levels of serum ALT and AST, but the ALT and AST levels of high-dose and middle-dose group of H. caudigerum TL after stir-baking with sand were higher than that of H. caudigerum TL without stir-baking with sand. The results revealed that the stir-baking with sand could effectively relieve diarrhea effect of H. caudigerum TL, while it also reduces the hepatoprotection of H. caudigerum TL.

An Oral Microbial Biomarker for Early Detection of Recurrence of Oral Squamous Cell Carcinoma.

Changes in the oral microbiome are associated with oral squamous cell carcinoma (OSCC). Oral microbe-derived signatures have been utilized as markers of OSCC. However, the structure of the oral microbiome during OSCC recurrence and biomarkers for the prediction of OSCC recurrence remains unknown. To identify OSCC recurrence-associated microbial biomarkers for the prediction of OSCC recurrence, we performed 16S rRNA amplicon sequencing on 54 oral swab samples from OSCC patients. Differences in bacterial compositions were observed in patients with vs without recurrence. We found that Granulicatella, Peptostreptococcus, Campylobacter, Porphyromonas, Oribacterium, Actinomyces, Corynebacterium, Capnocytophaga, and Dialister were enriched in OSCC recurrence. Functional analysis of the oral microbiome showed altered functions associated with OSCC recurrence compared with nonrecurrence. A random forest prediction model was constructed with five microbial signatures including Leptotrichia trevisanii, Capnocytophaga sputigena, Capnocytophaga, Cardiobacterium, and Olsenella to discriminate OSCC recurrence from original OSCC (accuracy = 0.963). Moreover, we validated the prediction model in another independent cohort (46 OSCC patients), achieving an accuracy of 0.761. We compared the accuracy of the prediction of OSCC recurrence between the five microbial signatures and two clinicopathological parameters, including resection margin and lymph node counts. The results predicted by the model with five microbial signatures showed a higher accuracy than those based on the clinical outcomes from the two clinicopathological parameters. This study demonstrated the validity of using recurrence-related microbial biomarkers, a noninvasive and effective method for the prediction of OSCC recurrence. Our findings may contribute to the prognosis and treatment of OSCC recurrence.

In-silico target prediction by ensemble chemogenomic model based on multi-scale information of chemical structures and protein sequences.

Identification and validation of bioactive small-molecule targets is a significant challenge in drug discovery. In recent years, various in-silico approaches have been proposed to expedite time- and resource-consuming experiments for target detection. Herein, we developed several chemogenomic models for target prediction based on multi-scale information of chemical structures and protein sequences. By combining the information of a compound with multiple protein targets together and putting these compound-target pairs into a well-established model, the scores to indicate whether there are interactions between compounds and targets can be derived, and thus a target prediction task can be completed by sorting the outputted scores. To improve the prediction performance, we constructed several chemogenomic models using multi-scale information of chemical structures and protein sequences, and the ensemble model with the best performance was used as our final model. The model was validated by various strategies and external datasets and the promising target prediction capability of the model, i.e., the fraction of known targets identified in the top-k (1 to 10) list of the potential target candidates suggested by the model, was confirmed. Compared with multiple state-of-art target prediction methods, our model showed equivalent or better predictive ability in terms of the top-k predictions. It is expected that our method can be utilized as a powerful computational tool to narrow down the potential targets for experimental testing.

Cross-reactivity of sIgE to mite and shrimp induced allergies in different age groups and clinical profiles of shrimp sIgE in vegetarians.

The sensitization to house dust mites (HDMs) and shrimps affects the development of hypersensitivity with an increase in age. Due to the cross-reactivity between shellfish and HDMs, HDMs were considered as the primary sensitizer for shellfish allergy. Thus, vegetarians might be sensitized to shrimp through the inadvertent inhalation of HDMs. Therefore, we assessed the prevalence of shrimp or mite allergy among different age groups and vegetarians. The serum specific-IgE (sIgE) level of HDMs and shrimp in 60 children/adolescence (un-adults), 30 adults, 30 elderly, and four vegetarian adults patients were measured. The sera with sIgE levels greater than 3.5 kUA/L were cross-reactivity examined. We found that HDMs induced higher sIgE than shrimp in un-adults. In contrast, shrimp-induced sIgE was higher in the adults and elderly patients. Moreover, adults were more frequently sensitized to shrimp and mite at the same time compared with the un-adult or elderly groups. The mite-Der p 10 not only displayed high cross-reactivity to the shrimp-Pen a 1 in all age groups and vegetarians but functioned as the major allergen to sensitize un-adults. Overall, the level of mite or shrimp sIgE is influenced by alterations in age, and vegetarians are at risk of shrimp sensitization via cross-reactivity between shrimp and mite.

Improved stability and oral bioavailability of Ganneng dropping pills following transforming lignans of herpetospermum caudigerum into nanosuspensions.

The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC0-t, Cmax and decrease in Tmax when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.