Quercetin nanocrystals for bioavailability enhancement: impact of different functional stabilizers on in vitro/in vivo drug performances.

The purpose of this study was to investigate the impact of different functional stabilizers on in vitro/in vivo drug performances after oral administration of drug nanocrystals. Quercetin nanocrystals (QT-NCs) respectively stabilized by five types of functional stabilizers, including hydroxypropyl methyl cellulose E15 (HPMC E15), poloxamer 407 (P407), poloxamer 188 (P188), D-α-tocopherol polyethylene glycol succinate (TPGS), and glycyrrhizin acid (GL), were fabricated by wet media milling technique. The particle size, morphology, physical state, drug solubility, drug dissolution in vitro, and orally pharmacokinetic behaviors of all QT-NCs were investigated. All QT-NCs with similar particle size about 200 nm were obtained by controlling milling speed and milling time. No significant differences in particles shape and crystalline nature were found for QT-NCs stabilized by different functional stabilizers. But the solubility and dissolution of QT-NCs were significantly influenced by the different functional stabilizers. The AUC0∼t of all QT-NCs after oral administration was in the following order: QT-NCs/P188 ≈ QT-NCs/HPMC E15 > QT-NCs/GL > QT-NCs/P407 ≈ QT-NCs/TPGS, and the Cmax showed an order of QT-NCs/P407 > QT-NCs/P188 ≈ QT-NCs/GL > QT-NCs/HPMC E15 > QT-NCs/TPGS. Both of QT-NCs/P407 and QT-NCs/TPGS exhibited faster oral absorption with Tmax at 0.5 h and 0.83 h, respectively, while the other three QT-NCs (QT-NCs/P188, QT-NCs/GL and QT-NCs/HPMC E15) showed a relatively slow absorption with same Tmax at 5.33 h. The longest MRT0∼t (11.72 h) and t1/2z (32.22 h) were observed for QT-NCs/HPMC E15. These results suggested that the different functional stabilizers could significantly influence on drug solubility, drug dissolution in vitro and orally pharmacokinetic behavior of QT-NCs, and it is possible to alter the drug dissolution in vitro, oral absorption and drug retention in vivo by changing the type of functional stabilizers in NCs preparation.

[Preparation and intestinal absorption mechanism of self-assembled nanoparticles of Herpetospermum caudigerum].

In this experiment, the micro-precipitation method was used to prepare self-assembled nanoparticles of Herpetospermum caudigerum Wall.(MP-SAN). The process was optimized using average particle size and polydispersity index(PDI)as evaluation indexes. The mean particle size, PDI,zeta potential, and microstructure of MP-SAN were characterized. The intestinal absorption mechanism of dehydrodiconiferyl alcohol(DA)and herpetrione(Her)in MP-SAN was investigated through single-pass intestinal perfusion in rats. The optimized process parameters for producing MP-SAN were a stirring speed of 800 r·min~(-1),stirring time of 5 min, and rotary evaporation temperature of 40℃. The resulting MP-SAN exhibited a spherical-like structure and uniform morphology, with a mean particle size of(267.63±13.27) nm, a PDI of 0.062 0±0.043 9,and a zeta potential of(-46.18±3.66) mV. The absorption rate constant(K_a)and apparent permeability coefficient(P_(app))of DA in the ileal segment were significantly higher than those in the jejunal segment(P<0.05). However, there was no significant difference in the absorption of Her between the ileal and jejunal segments. Intestinal absorption parameters of DA and Her tended to increase with increasing drug concentration. Specifically, the K_a and P_(app) of DA in MP-SAN in the high-concentration group were significantly higher than those in the low-concentration group(P<0.01). The addition of verapamil, a P-glycoprotein inhibitor, did not significantly affect the intestinal absorption of DA and Her. However, the absorption of both DA and Her in MP-SAN was significantly increased by the addition of indomethacin(P<0.05),suggesting that DA and Her may be substrates for multidrug resistance-associated protein 2.

Powering mesoporous silica nanoparticles into bioactive nanoplatforms for antibacterial therapies: strategies and challenges.

Bacterial infection has been a major threat to worldwide human health, in particular with the ever-increasing level of antimicrobial resistance. Given the complex microenvironment of bacterial infections, conventional use of antibiotics typically renders a low efficacy in infection control, thus calling for novel strategies for effective antibacterial therapies. As an excellent candidate for antibiotics delivery, mesoporous silica nanoparticles (MSNs) demonstrate unique physicochemical advantages in antibacterial therapies. Beyond the delivery capability, extensive efforts have been devoted in engineering MSNs to be bioactive to further synergize the therapeutic effect in infection control. In this review, we critically reviewed the essential properties of MSNs that benefit their antibacterial application, followed by a themed summary of strategies in manipulating MSNs into bioactive nanoplatforms for enhanced antibacterial therapies. The chemically functionalized platform, photo-synergized platform, physical antibacterial platform and targeting-directed platform are introduced in details, where the clinical translation challenges of these MSNs-based antibacterial nanoplatforms are briefly discussed afterwards. This review provides critical information of the emerging trend in turning bioinert MSNs into bioactive antibacterial agents, paving the way to inspire and translate novel MSNs-based nanotherapies in combating bacterial infection diseases.

Herpetetrone nanosuspensions enhance drug solubility and bioavailability to improve anti-hepatic fibrosis effects.

The aim of this study was to enhance the dissolution rate and oral bioavailability of herpetetrone (HPT) by preparing nanosuspensions (NSs) and evaluate the changes in its anti-hepatic fibrosis effect. Herpetetrone nanosuspension (HPT-NS) was prepared using the ultrasound-precipitation technique, and characterised on the basis of mean diameter, zeta potential (ZP), encapsulation efficiency percent (EE%), scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD). In addition, the pharmacokinetics and anti-hepatic fibrosis activity were evaluated. HPT-NS prepared with the optimised formulation was found to be spherical with mean diameter of 177.48 ± 6.13 nm, polydispersity index (PDI) of 0.108 ± 0.002 and ZP of -17.28 ± 2.02 mV. The EE (m/m, %) was 83.25 ± 0.27. XRPD analyses confirmed that the amorphous state of HPT in HPT-NS remained unchanged. The dissolution rate of HPT-NS was significantly higher than that of HPT coarse suspensions (HPT-CSs). Following oral administration, Cmax and AUC0-t of HPT-NS showed a significant increase (p < 0.05). In vitro, HPT inhibited the proliferation of HSC-T6 cells and induced apoptosis by up-regulating the expression of Bax proteins and down-regulating the expression of Bcl-2 and TGF-ß1 proteins. Compared with HPT-CS, HPT-NS exhibited a more pronounced anti-fibrotic effect. HPT-NS, as a new drug formulation designed to improve the solubility and bioavailability of the drug, shows promising potential in enhancing the anti-liver fibrosis effect.

Sponge-liked Silica Nanoporous Particles for Sustaining Release and Long-Term Antibacterial Activity of Natural Essential Oil.

To improve the sustained release and long-term antibacterial activity of Chimonanthus nitens Oliv. essential oil (CEO), novel sponge-liked nanoporous silica particles (SNP) were synthesized via the soft template method, which was employed as a biocompatible carrier to prepare spong-liked nanoporous silica particles loading with CEO (CEO-SNP) through physical adsorption. The structure and properties of the samples were characterized via N2 adsorption/desorption measurements, thermogravimetry (TGA), Fourier transform infrared, SEM and TEM. The result showed that the SNP exhibited an excellent loading capability of CEO up to 76.3%. The thermal stability and release behavior of the CEO were significantly improved via the physical adsorption of the SNP materials. The release profile of CEO was in accordance with the first-order kinetic model, which meant that the release mechanism was drug Fick's diffusion. The antibacterial evaluation results demonstrated that the CEO-SNP exhibited strong antibacterial activity against S. aureus, E. coli and P. aeruginosa. The antibacterial results have shown that the CEO-SNP could destroy the cell structure of bacteria, and result in the generation of oxidative stress and the release of nucleic acid. After storage of 30 d at 25 °C, the CEO-SNP still had the stronger antibacterial activity towards S. aureus, E. coli and P. aeruginosa in comparison with CEO. Therefore, the sponge-like silica nanoporous particles seemed to be a promising carrier for long-term stability and antibacterial delivery of CEO.

[Preparation and in vitro release of quercetin nanocrystals self-stabilized Pickering emulsion].

A new quercetin nanocrystals self-stabilized Pickering emulsion(QT-NSSPE) was prepared by high-pressure homogenization combined with probe ultrasonic method. The influences of oil fraction, quercetin(QT) concentration, and pH of water phase on the formation of QT-NSSPE were investigated. On this basis, the QT-NSSPE prepared under optimal conditions was evaluated in terms of microstructure, stability, and in vitro release and the droplet size and drug loading were 15.82 µm and 4.87 mg·mL~(-1), respectively. The shell structure formed by quercetin nanocrystals(QT-NC) on the emulsion droplet surface was observed under a scanning electron microscope(SEM). X-ray diffraction(XRD) showed that the crystallinity of adsorbed QT-NC decreased significantly as compared with the raw QT. There were not significant changes of QT-NSSPE properties after 30 days of storage at room temperature. The in vitro release experiment confirmed that QT-NSSPE has a higher accumulative release rate than the raw QT. All these results indicated that QT-NSSPE has a great stability and a satisfactory in vitro release behavior, which is a promising new oral delivery system for QT.

Development of herpetrione nanosuspensions stabilized by glycyrrhizin for enhancing bioavailability and synergistic hepatoprotective effect.

The objective of this study was to develop novel herpetrione (HPE) nanosuspensions stabilized by glycyrrhizin (HPE NSs/GL) for enhancing bioavailability and hepatoprotective effect of HPE. HPE NSs/GL were prepared by wet media milling method and then systemically evaluated by particle size analysis, scanning electronic microscopy (SEM), X-ray powder diffraction (XRPD), dissolution test, pharmacokinetics, and hepatoprotective effect. HPE-NSs stabilized by poloxamer 407 (HPE NSs/P407) were also prepared and used as a reference for comparison. HPE NSs/GL and HPE-NSs/P407 with similar particle sizes around 450 nm and PDI less than 0.2 were successfully prepared and both of them appeared to be spherical under SEM. The XRPD results demonstrated that HPE in both HPE NSs/GL and HPE NSs/P407 was presented in the amorphous state and the addition of GL or P407 and the milling process didn't alter the physical state of HPE. The dissolution and pharmacokinetic studies demonstrated that HPE NSs/GL exhibited significant enhancement in drug dissolution (72.44% within 24 h) and AUC0-t (24.91 ± 3.3 mg/L·h) as compared to HPE coarse suspensions (HPE CS, 34.19% & 13.07 ± 1.02 mg/L·h), but was similar with those of HPE NSs/P407 (80.06% & 26.75 ± 4.06 mg/L•h). Moreover, HPE NSs/GL exhibited significantly better hepatoprotective effect as compared to HPE CS and HPE NSs/P407 as indicated by the lowering of the elevated serum ALT and AST levels and the improvement of the hepatic morphology and architecture, which might be attributed to the improved bioavailability of HPE, and synergistic hepatoprotective effect of GL via alleviating inflammation evidenced by the significant decreased hepatic levels of inflammatory cytokines IL-1ß, IL-6 and TNF-α. It could be concluded that GL might be an effective stabilizer for preparing HPE NSs, and HPE NSs/GL is a potential formulation strategy for improving oral bioavailability and hepatoprotective effect of HPE.

Topical delivery of pluronic F127/TPGS mixed micelles-based hydrogel loaded with glycyrrhizic acid for atopic dermatitis treatment.

OBJECTIVE: The purpose of this study was to develop pluronic F127/d-a-tocopheryl polyethylene glycol 1000 succinate mixed micelles-based hydrogel (MMs-gel) for topical delivery of glycyrrhizic acid (GL) to improve its skin permeability and atopic dermatitis (AD) treatment. SIGNIFICANCE: GL loaded MMs-gel (GL-MMs-gel) could be potentially used as a promising nanocarrier for the treatment of AD. METHODS: GL-MMs were prepared by thin film hydration method and then loaded into carbopol gel. The formulation of GL-MMs-gel was optimized by full factorial design and systematically characterized for drug content, pH, spreadability, in vitro drug release and percutaneous permeation, etc. The therapeutic effect of GL-MMs-gel was also investigated in AD-like skin lesion model in BALB/c mice and compared with GL solution-based gel (GL-sol-gel). RESULTS: Spherical GL-MMs with particle size of ∼30 nm were successfully incorporated into carbopol gel to form GL-MMs-gel with drug content of (98.80 ± 1.30) %, pH of 6.0 ± 0.08, and spreadability of (7.1 ± 0.2) cm. In vitro drug release profile of GL-MMs-gel exhibited a sustained-release behavior. The permeation flux for GL-MMs-gel (5.15 ± 0.33 µg/cm2/h) was significantly higher than that of GL-sol-gel (3.08 ± 0.34 µg/cm2/h) and GL-MMs-gel increased the accumulative amounts of GL in rats' skin 8.41 times than GL-sol-gel. The GL-MMs-gel was more effective than GL-sol-gel in suppressions of various AD symptoms including skin lesions, edema, high IgE levels, epidermal hyperplasia, and mast cell infiltration. CONCLUSION: All results revealed that MMs-gel could be a promising carrier for topical delivery of GL for the treatment of AD.

Nanocrystals based mucosal delivery system: research advances.

Nanocrystal technology is a new way to increase the solubility and bioavailability of poorly soluble drugs. As an intermediate preparation technology, nanocrystals are widely used in drug delivery for oral, venous, percutneous and inhalation administration, which exhibits a broad application prospect. By referring to the domestic anforeign literatures, this paper mainly reviews the preparation methods of nanocrystals for poorly soluble natural products and its application in the mucosal delivery for skin, eye, oral cavity and nasal cavity. This can provide the reference for the research and development of nanocrystal technology in natural product preparations.

Glycyrrhizic acid-based self-assembled micelles for improving oral bioavailability of paeoniflorin.

BACKGROUND: Paeoniflorin (Pae), a water-soluble monoterpene glucoside, has high potential clinical value in autoimmune and inflammatory diseases. However, the extremely low oral bioavailability of Pae (approximately 3%-4%) limits its formulation development and clinical application. This study aimed to develop micelles using the glycyrrhizic acid (GL) as the carrier to improve the oral absorption of Pae. METHODS: Pae-loaded GL micelles were prepared by the ultrasonic dispersion method and its formulation was optimized by single-factor tests. Characterizations of Pae-loaded GL micelles including particle size, zeta potential, entrapment efficiency (EE), drug loading (DL), morphology, and drug release in vitro were carried out. The single-pass intestinal perfusion and pharmacokinetic studies of Pae-loaded GL micelles were also evaluated in rats and compared with Pae solution and the mixed solution of Pae and GL. RESULTS: The optimized Pae-loaded GL micelles had EE of (42.21 ± 0.89)%, particle size of (58.89 ± 4.24) nm with PDI of (0.194 ± 0.010), zeta potential of (-24.40 ± 1.90) mV. Pae-loaded GL micelles showed a nearly spherical shape under TEM. Drug release of micelles demonstrated a delayed drug release compared to Pae solution. The single-pass intestinal perfusion study showed a significantly higher permeability of Pae in duodenum (p < 0.05), jejunum (p < 0.05), ileum (p < 0.01) and colon (p < 0.01) intestine after perfusion of Pae-loaded GL micelles as compared to Pae solution. The in vivo pharmacokinetics demonstrated that the Cmax and AUC0-t values of Pae-loaded GL micelles were approximately 2.18- and 3.64-fold superior than the Pae solution. CONCLUSION: These results suggested GL could be a potential carrier for the oral delivery of Pae.

[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.

Formulation of pluronic F127/TPGS mixed micelles to improve the oral absorption of glycyrrhizic acid.

Background: Glycyrrhizic acid (GL), a pentacyclic triterpenoid glycoside, has been used as a hepatoprotective agent for the treatment of acute and chronic hepatitis. However, its poor solubility and permeability across the gastrointestinal mucosa limit its clinical efficacy. This study aimed to develop mixed micelles based on pluronic F127 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) to improve the oral bioavailability of GL.Methods: GL loaded pluronic F127/TPGS mixed micelles (GL-F127/TPGS-MMs) were prepared by thin film hydration method, and their physicochemical properties including particle size, zeta potential, entrapment efficiency (EE), drug loading (DL), X-ray diffraction (XRD) analysis, differential scanning calorimetry (DSC), and drug release were characterized. Furthermore, the pharmacokinetic and biodistribution studies of GL-F127/TPGS-MMs were evaluated in rats and compared with GL solution.Results: GL-F127/TPGS-MMs were found to be of spherical shape with particle size of (27.41 ± 4.90) nm, EE% of 95.38% and DL% of 12.99%. The results of XRD and DSC indicated that GL was encapsulated in the micelles. Drug release of GL-F127/TPGS-MMs demonstrated a sustained release behavior as compared to GL solution. The pharmacokinetic and biodistribution studies showed a significantly higher oral absorption and liver accumulation of glycyrrhetinic acid (GA) after oral administration of GL-F127/TPGS-MMs as compared to GL solution.Conclusion: These results suggested F127/TPGS-MMs might be a potential nanocarrier for oral delivery of GL.

[Preparation and in vitro quality evaluation of self-microemulsion co-loaded with tenuifolin and ß-asarone].

To prepare and optimize the self-microemulsion co-loaded with tenuifolin and ß-asarone(TF/ASA-SMEDDS) and evaluate its quality. The prescription compositions of TF/ASA-SMEDDS were screened by solubility test, single factor test and pseudo-tern-ary phase diagram, and the prescriptions were further optimized by Box-Behnken response surface method, with the drug loading and particle size as the evaluation indexes. Then the optimized TF/ASA-SMEDDS was evaluated for emulsified appearance, particle size, morphology and drug release in vitro. The optimized prescription for TF/ASA-SMEDDS was as follows: caprylic citrate triglyceride polyoxyethylene castor oil-glycerol(10.8∶39.2∶50), drug loading of(5.563±0.065) mg·g~(-1) for tenuifolin and(5.526±0.022) mg·g~(-1) for ß-asarone; uniform and transparent pan-blue nanoemulsion can be formed after emulsification, with particle size of(28.84±0.44) nm. TEM showed that TF/ASA-SMEDDS can form spherical droplets with a uniform particle size after emulsification; In vitro release test results showed that the drug release rate and cumulative release of tenuifolin and ß-asarone were significantly improved. The preparation process of TF/ASA-SMEDDS was simple and can effectively improve in vitro release of tenuifolin and ß-asarone.

[Preparation and in vitro release of ginkgolide B nanosuspension].

To prepare ginkgolide B nanosuspension(GB-NS), and investigate its dissolution behaviors in vitro. The miniaturized media milling method was used to prepare nanosuspensions, with average particle size and polydispersity index as the evaluation indexes. The formulation and process of GB-NS were optimized by single factor experiment and Box-Behnken design-response surface method. The morphology was observed by scanning electron microscope(SEM), and thecrystallinity of GB-NS was investigated by X-rays diffraction(XRD). The paddle method was used to study the dissolution of GB-NS in vitro. The mean particle size of optimized GB-NS was(180±7) nm, with a polydispersity index of 0.196±0.036. SEM showed that GB-NS was rod-like or irregular granular. XRD showed that the crystallinity of GB-NS was significantly reduced compared with GB raw material. The cumulative dissolution rate of GB-NS reached 90% in 30 min, which was higher than that of GB raw material. The findings suggested that the miniaturized media milling method was simple, efficient and feasible to prepare GB-NS. And the dissolution rate of GB was significantly improved by nanosuspension technology.

[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.