Raspberry-liked Pickering emulsions based inulin microparticles for enhanced antibacterial performance of essential oils.

Pickering emulsions seem to be an effective strategy for encapsulation and stabilization of essential oils. In this work, a novel raspberry-liked Pickering emulsion (RPE) loading Mosla chinensis 'Jiangxiangru' essential oil (MJO) was successfully engineered by using ethyl lauroyl arginate (ELA) decorated nanosilica (ELA-NS) as particles emulsifier. And the ELA-NS-stabilized MJO Pickering emulsion (MJO-RPE) was further prepared into inulin-based microparticles (MJO-RPE-IMP) by spray-drying, using inulin as matrix formers. The concentration of ELA-NS could affect the formation and stabilization of MJO-RPE, and the colloidal behavior of ELA-NS could be modulated at the interfaces with concentration of ELA, thus providing unique role on stabilization of MJO-RPE. The results indicated that the MJO-RPE stabilized ELA-NS with 2 % NS modified by 0.1 % ELA had long-term stability. MJO-RPE exhibited a raspberry-liked morphology on the surface, attributed to ELA-NS covered in the droplet surface. The inulin-based matrix formers could effectively prevent MJO-RPE from agglomeration or destruction during spray-drying, and 100 % concentration of inulin based microparticles formed large composite particles with high loading capacity (98.54 ± 1.11 %) and exhibited superior thermal stability and redispersibility of MJO-RPE. The MJO-RPE exhibited strong antibacterial efficacy against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Pseudomonas aeruginosa (P. aeruginosa), owing to the adhesion to bacterial membrane dependent on the raspberry-liked surface of MJO-RPE, whose minimum inhibitory concentration (MIC) of the above three bacteria were (0.3, 0.45, and 1.2 µL/mL), respectively, lower than those (0.45, 0.6 and 1.2 µL/mL) of MJO. Therefore, the Pickering emulsion composite microparticles seemed to be a promising strategy for enhancing the stability and antibacterial activity of MJO.

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.

Fabrication and in vitro/vivo evaluation of quercetin nanocrystals stabilized by glycyrrhizic acid for liver targeted drug delivery.

The purpose of this study was to design novel drug nanocrystals (NCs) stabilized by glycyrrhizic acid (GL) for achieving liver targeted drug delivery due to the presence of GL receptor in the hepatocytes. Quercetin (QT) exhibits good pharmacological activities for the treatment of liver diseases, including liver steatosis, fatty hepatitis, liver fibrosis, and liver cancer. It was selected as a model drug owing to its poor water solubility. QT NCs stabilized by GL (QT-NCs/GL) were fabricated by wet media milling technique and systemically evaluated. QT-NCs stabilized by poloxamer 188 (QT-NCs/P188) were prepared as a reference for comparison of in vitro and in vivo performance with QT-NCs/GL. QT-NCs/GL and QT-NCs/P188 with similar particle size around 130 nm were successfully fabricated by wet media milling technique. Both of QT-NCs/GL and QT-NCs/P188 showed irregular particles and short rods under SEM. XRPD revealed that QT-NCs/GL and QT-NCs/P188 remained in crystalline state with reduced crystallinity. QT-NCs/GL and QT-NCs/P188 exhibited significant solubility increase and drug release improvement of QT as compared to raw QT. No significant difference for the plasma concentration-time curves and pharmacokinetic parameters of QT were found following intravenous administration of QT-NCs/GL and QT-NCs/P188. However, a significantly higher liver distribution of QT following intravenous administration of QT-NCs/GL was observed in comparison to QT-NCs/P188, indicating QT-NCs stabilized by GL could achieve liver targeted delivery of QT. It could be concluded that GL used as stabilizer of QT NCs have a great potential for liver targeted drug delivery.

Antifungal activity and potential mechanism of action of Huangqin decoction against Trichophyton rubrum.

Introduction. Trichophyton rubrum is a major causative agent of superficial dermatomycoses such as onychomycosis and tinea pedis. Huangqin decoction (HQD), as a classical traditional Chinese medicine formula, was found to inhibit the growth of common clinical dermatophytes such as T. rubrum in our previous drug susceptibility experiments.Hypothesis/Gap Statement. The antifungal activity and potential mechanism of HQD against T. rubrum have not yet been investigated.Aim. The aim of this study was to investigate the antifungal activity and explore the potential mechanism of action of HQD against T. rubrum.Methodology. The present study was performed to evaluate the antifungal activity of HQD against T. rubrum by determination of minimal inhibitory concentrations (MICs), minimal fungicidal concentrations (MFCs), mycelial growth, biomass, spore germination and structural damage, and explore its preliminary anti-dermatophyte mechanisms by sorbitol and ergosterol assay, HPLC-based ergosterol test, enzyme-linked immunosorbent assay and mitochondrial enzyme activity test.Results. HQD was able to inhibit the growth of T. rubrum significantly, with an MIC of 3.125 mg ml-1 and an MFC of 12.5 mg ml-1. It also significantly inhibited the hyphal growth, conidia germination and biomass growth of T. rubrum in a dose-dependent manner, and induced structural damage in different degrees for T. rubrum cells. HQD showed no effect on cell wall integrity, but was able to damage the cell membrane of T. rubrum by interfering with ergosterol biosynthesis, involving the reduction of squalene epoxidase (SE) and sterol 14α-demethylase P450 (CYP51) activities, and also affect the malate dehydrogenase (MDH), succinate dehydrogenase (SDH) and ATPase activities of mitochondria.Conclusion. These results revealed that HQD had significant anti-dermatophyte activity, which was associated with destroying the cell membrane and affecting the enzyme activities of mitochondria.

Pore engineering of micro/mesoporous nanomaterials for encapsulation, controlled release and variegated applications of essential oils.

Essential oils have become increasingly popular in fields of medical, food and agriculture, owing to their strongly antimicrobial, anti-inflammation and antioxidant effects, greatly meeting demand from consumers for healthy and safe natural products. However, the easy volatility and/or chemical instability of active ingredients of essential oils (EAIs) can result in the loss of activity before realizing their functions, which have greatly hindered the widely applications of EAIs. As an emerging trend, micro/mesoporous nanomaterials (MNs) have drawn great attention for encapsulation and controlled release of EAIs, owing to their tunable pore structural characteristics. In this review, we briefly discuss the recent advances of MNs that widely used in the controlled release of EAIs, including zeolites, metal-organic frameworks (MOFs), mesoporous silica nanomaterials (MSNs), and provide a comprehensive summary focusing on the pore engineering strategies of MNs that affect their controlled-release or triggered-release for EAIs, including tailorable pore structure properties (e.g., pore size, pore surface area, pore volume, pore geometry, and framework compositions) and surface properties (surface modification and surface functionalization). Finally, the variegated applications and potential challenges are also given for MNs based delivery strategies for EAIs in the fields of healthcare, food and agriculture. These will provide considerable instructions for the rational design of MNs for controlled release of EAIs.

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.

Rambutan-liked Pickering emulsion stabilized by cellulose nanocrystals for enhancing anti-bacterial activity and anti-inflammatory effect of Chimonanthus nitens Oliv. essential oil.

Owing to volatility and poor water solubility, the medical application of Chimonanthus nitens Oliv. essential oil (CEO) in the fields of medicine was strictly limited. To tackle this problem, a novel CEO loaded rambutan-liked Pickering emulsion (CEO-RPE) with a spiky surface was effectively designed by coating with carboxymethyl cellulose sodium modified cellulose nanocrystals (CCN) as stabilizer. The effect of CCN concentration on the formation and stabilization of CEO-RPE was investigated. The results showed that CEO-RPE stabilized by 1 % CCN had a smaller droplet size and exhibited a rambutan-liked surface, and was stabilized against concentrated salt and high pH condition due to the steric barrier of CCN that covered in the droplet surface. Subsequently, the antibacterial performance of CEO-RPE was investigated against E. coli, S. aureus, P. aeruginosa, and S. pneumoniae by determining the minimum inhibitory concentration (MIC). The results showed that the CEO-RPE exhibited higher antibacterial activity compared to CEO, which could be attributed to its effective adhesion to the cell membrane of bacteria. In addition, the results of anti-inflammatory experiments showed that CEO-RPE also exhibited strong anti-inflammatory effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. Therefore, the CCN stabilized rambutan-liked Pickering emulsion seemed to be a promising strategy to increase the antibacterial and anti-inflammatory activity of CEO.

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.

Mucus-penetrating dendritic mesoporous silica nanoparticle loading drug nanocrystal clusters to enhance permeation and intestinal absorption.

Multiple gastrointestinal barriers (mucus clearance and epithelium barrier) are the main challenges in the oral administration of nanocarriers. To achieve efficient mucus penetration and epithelial absorption, a novel strategy based on mesoporous silica nanoparticles with dendritic superstructure, hydrophilicity, and nearly neutral-charged modification was designed. The mPEG covalently grafted dendritic mesoporous silica nanoparticles (mPEG-DMSNs) had a particle size of about 200 nm and a loading capacity of up to 50% andrographolide (AG) as a nanocrystal cluster in the mesoporous structure. This dual strategy of combining with the surface topography structure and hydrophilic modification maintained a high mucus permeability and showed an increase in cell absorption. The mPEG-DMSN formulation also exhibited effective transepithelial transport and intestinal tract distribution. The pharmacokinetics study demonstrated that compared with other AG formulations, the andrographolide nanocrystals-loaded mPEG-DMSN (AG@mPEG-DMSN) exhibited much higher bioavailability. Also, AG@mPEG-DMSN could significantly improve the in vitro and in vivo anti-inflammatory efficacy of AG. In summary, mPEG-DMSN offers an interesting strategy to overcome the mucus clearance and epithelium barriers of the gastrointestinal tract.

Exploring the translocation behaviours in vivo of herpetrione amorphous nanoparticles via oral delivery.

Nanotechnology has been a primary strategy to enhance oral bioavailability of poorly water soluble drugs. However, the limited information in vivo fate of impedes the development of nanoparticles via the oral delivery, especially the amorphous nanoparticles with high energy states are rarely reported. This study is to track the translocation of oral herpetrione amorphous nanoparticles (HPE-ANPs). We prepare amorphous particles (ANPs) of various sizes (200 nm and 450 nm), which are embedded with an aggregation-caused quenching (ACQ) dyes for tracking the intact nanoparticles. Nanoparticles remain in the gastrointestinal tract (GIT) for 8 h following oral administration, suggesting that most ANPs was mainly degraded or absorbed in the small intestine. Ex vivo imaging shows that the fluorescent signals are observed in the GIT and liver but not in other organs, which attributed to low absorption of integral nanoparticles. Besides, HPE-ANPs may be directly interact with GIT epithelia, and ileum provides better absorption than the jejunum. Cellular studies prove that integral HPE-ANPs can be taken up by enterocyte, while it penetrates cell monolayers only small amounts. In conclusion, we speculate that the drug in the form of integral nanoparticles and small molecules may be co-absorbed to improve bioavailability in vivo.

Effects of novel Fufang Biejia Ruangan Tablets with sheep placenta as substitute for Hominis Placenta on CCl4-induced liver fibrosis.

Objective: Fufang Biejia Ruangan Tablet (FBRT) is widely used for the treatment of liver fibrosis. However, Hominis Placenta (HP), as an important adjuvant of FBRT, has been restricted for medicinal using due to the limited availability, ethical controversy and safety issues. The present study aimed to investigate the therapeutic effects of novel FBRT (N-FBRT) with sheep placenta (SP) as substitute for HP on liver fibrosis and explore its possible mechanisms. Different dosages of SP in N-FBRT were also evaluated. Methods: Rats were subcutaneously injected with CCl4 to induce liver fibrosis and then treated with N-FBRT and FBRT. The anti-hepatic fibrosis effect was determined based on biomarkers analysis of liver function and hepatic fibrosis, and the liver pathology was visualized by H&E staining and Masson staining. The oxidative stress and inflammatory cytokines were also detected. Immunohistochemical staining of α-SMA, real time PCR and Western blotting were performed to evaluate hepatic stellate cells (HSCs) activation and TGF-ß1/Smad signaling pathway. Results: N-FBRT and FBRT could ameliorate CCl4-induced liver fibrosis and improve liver function, as evidenced by lowering serum biomarkers levels of liver function and hepatic fibrosis, and decreasing hepatic Hyp content and collagen deposition, and improving the hepatic morphology and architecture changes. Moreover, the anti-liver fibrosis effect was better when the dosage of SP used in N-FBRT was 1/2 of HP in FBRT. Administration of N-FBRT markedly alleviated oxidative stress and inflammatory cytokines, and inhibited α-SMA expression. Furthermore, the mRNA expression of Col I, Col III, α-SMA and TGF-ß1, and proteins expression of α-SMA, TGF-ß1, Smad2/3 and p-Smad2/3 were significantly down-regulated by N-FBRT treatment. Conclusion: SP can be used as substitute for HP to prepare N-FBRT for the treatment of liver fibrosis and the anti-liver fibrosis effect of N-FBRT is achieved by eliminating oxidative stress and inflammation, and inhibiting HSCs activation and ECM production by blocking TGF-ß1/Smad signaling pathway.

Fabrication and In Vitro/Vivo Evaluation of Drug Nanocrystals Self-Stabilized Pickering Emulsion for Oral Delivery of Quercetin.

The aim of this study was to develop a new drug nanocrystals self-stabilized Pickering emulsion (NSSPE) for improving oral bioavailability of quercetin (QT). Quercetin nanocrystal (QT-NC) was fabricated by high pressure homogenization method, and QT-NSSPE was then prepared by ultrasound method with QT-NC as solid particle stabilizer and optimized by Box-Behnken design. The optimized QT-NSSPE was characterized by fluorescence microscope (FM), scanning electron micrograph (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The stability, in vitro release, and in vivo oral bioavailability of QT-NSSPE were also investigated. Results showed that the droplets of QT-NSSPE with the size of 10.29 ± 0.44 µm exhibited a core-shell structure consisting of a core of oil and a shell of QT-NC. QT-NSSPE has shown a great stability in droplets shape, size, creaming index, zeta potential, and QT content during 30 days storage at 4, 25, and 40 °C. In vitro release studies showed that QT-NSSPE performed a better dissolution behavior (65.88% within 24 h) as compared to QT-NC (50.71%) and QT coarse powder (20.15%). After oral administration, the AUC0-t of QT-NSSPE was increased by 2.76-times and 1.38 times compared with QT coarse powder and QT-NC. It could be concluded that NSSPE is a promising oral delivery system for improving the oral bioavailability of QT.

To Enhance Mucus Penetration and Lung Absorption of Drug by Inhalable Nanocrystals-In-Microparticles.

To effectively achieve the pulmonary delivery for curcumin (CN), novel inhalable mucus-penetrating nanocrystal-based microparticles (INMP) were designed. The D-Tocopherol acid polyethylene glycol 1000 succinate (TPGS) modified CN nanocrystals (CN-NS@TPGS) were prepared by high pressure homogenization and further converted into nanocrystal-based microparticles (CN-INMP@TPGS) using spray-drying. It was demonstrated that CN-NS@TPGS exhibited little interaction with the negatively charged mucin due to a strong electrostatic repulsion effect and PEG hydrophilic chain, and exhibited a much higher penetration ability across the mucus layer compared with poloxamer 407 modified CN-NS (CN-NS@P407) and tween 80 modified CN-NS (CN-NS@TW80). The aerodynamic results demonstrated that the CN-INMP with 10% TPGS acting as the stabilizer presented a high FPF value, indicating excellent deposition in the lung after inhalation administration. Additionally, in vivo bioavailability studies indicated that the AUC(0-t) of CN-INMP@TPGS (2413.18 ± 432.41 µg/L h) were 1.497- and 3.32-fold larger compared with those of CN-INMP@TW80 (1612.35 ± 261.35 µg/L h) and CN-INMP@P407 (3.103 ± 196.81 µg/L h), respectively. These results indicated that the CN-INMP@TPGS were absorbed rapidly after pulmonary administration and resulted in increased systemic absorption. Therefore, the inhalable CN-INMP could significantly improve the bioavailability of CN after inhalation administration. The developed mucus-penetrating nanocrystals-in-microparticles might be regarded as a promising formulation strategy for the pulmonary administration of poorly soluble drugs.

[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.

[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.

The contribution of absorption of integral nanocrystals to enhancement of oral bioavailability of quercetin.

In this study, self-discriminating hybrid nanocrystals was utilized to explore the biological fate of quercetin hybrid nanocrystals (QT-HNCs) with diameter around 280 nm (QT-HNCs-280) and 550 nm (QT-HNCs-550) following oral and intravenous administration and the contribution of integral nanocrystals to oral bioavailability enhancement of QT was estimated by comparing the absolute exposure of integral QT-HNCs and total QT in the liver. Results showed that QT-HNCs could reside in vivo as intact nanocrystals for as long as 48 h following oral and intravenous administration. A higher accumulation of integral QT-HNCs in liver and lung was observed for both oral and intravenous administration of QT-HNCs. The particle size affects the absorption and biodistribution of integral QT-HNCs and total QT. As compared to QT-HNCs-550, QT-HNCs-280 with smaller particle size is more easily absorbed, but dissolves faster in vivo, leading to higher distribution of QT (146.90 vs. 117.91 h·µg/mL) but lower accumulation of integral nanocrystals (6.8 2e10 vs. 15.27e10 h·[p/s]/[µW/cm²]) in liver following oral administration. Due to its slower dissolution and enhanced recognition by RES, QT-HNCs-550 with larger diameter shows higher liver distribution for both of QT (1015.80 h·µg/mL) and integral nanocrystals (259.63e10 h·[p/s]/[µW/cm²]) than those of QT-HNCs-280 (673.82 & 77.66e10 h·[p/s]/[µW/cm²]) following intravenous administration. The absolute exposure of integral QT-HNCs in liver following oral administration of QT-HNCs are 8.78% for QT-HNCs-280 and 5.88% for QT-HNCs-550, while the absolute exposure of total QT for QT-HNCs-280 and QT-HNCs-550 are 21.80% and 11.61%, respectively. Owing to imprecise quantification method, a surprisingly high contribution of integral QT-HNCs to oral bioavailability enhancement of QT (40.27% for QT-HNCs-280 and 50.65% for QT-HNCs-550) was obtained. These results revealed significant difference in absorption and biodistrbution between integral nanocrystals and overall drugs following oral and intravenous administration of QT-HNCs, and provided a meaningful reference for the contribution of integral nanocrystals to overall bioavailability enhancement.

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.