Search

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.GL loaded MMs-gel (GL-MMs-gel) could be potentially used as a promising nanocarrier for the treatment of AD.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,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.All results revealed that MMs-gel could be a promising carrier for topical delivery of GL for the treatment of AD.

Background The vine stem of Spatholobus suberectus Dunn (S. suberectus), called “JiXueTeng”, has been used as a significant medicine for thousands of years in China. However, reliable field identification of this medicinal plant remains problematic, inaccurate identification may cause serious adverse effects in the functions of the drug and may affect the clinical medication reviews. Objective To ensure use of the exact medicine and implement protective legislation, it is imperative to obtain the chloroplast (cp) genome of S. suberectus, which can be used as a valuable resource for species identification and phylogenetic analysis. Methods In this study, the complete cp genomes of S. suberectus (152 173 bp (base pair)) and S. pulcher (151 099 bp) were assembled for the first time by using next-generation sequencing (NGS) technology to gain abundant information on the genus of Spatholobus. And some bioinformatics softwares were used for data filtering, assembling and analyzing. Results We found the G and C contents of S. suberectus and S. pulcher were close, 35.19% and 35.37%, respectively. The noncoding regions were more divergent than coding ones. Moreover, we revealed eight divergence hotspots (trnH, trnK-rbcL, trnL-rbcT, psbD-trnT, trnC-rpoB, atpI-atpH, ycf4, and trnL-rpl32) which might be used as candidate molecular markers for Spatholobus identification. The analysis of the phylogenetic relationship indicated that two Spatholobus species were clustered together and two Spatholobus species was sister to the Cajanus. Conclusion The findings of this study were conducive to species identification and phylogenetic research of Spatholobus and provided valuable resources for finding the substitution of S. suberectus. Highlights We assembled the complete cp genomes of S. suberectus and S. pulcher for the first by using next-generation sequencing.

In this work, superparamagnetic Fe3O4@SiO2 nanoparticles (NPs) with high saturation magnetization (Ms) were synthesized. The NPs had core-shell structures with magnetic Fe3O4 as the core and SiO2 as the shell. The magnetic core was firstly prepared with miniemulsion method, then SiO2 shell was synthesized by Stober method. Polyvinylpyrrolidone (PVP) modified Fe3O4@SiO2 NPs were a new adsorbent material for hydrophobic substances in water environments. The original and PVP modified Fe3O4@SiO2 NPs were characterized with transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectrometry (FT-IR), atomic force microscopy (AFM), as well as Brunauer–Emmet–Teller (BET). The Ms of the original and modified Fe3O4@SiO2 NPs were 30.78 emu·g−1 and 30.89 emu·g−1, respectively. XPS certified that PVP molecules were embedded in the shell of Fe3O4@SiO2 NPs, owing to PVP used in preparation of Fe3O4 nanocluster as a protective agent. After modification, besides in SiO2 shell, PVP was also found on the surface of Fe3O4@SiO2 NPs. AFM images showed that column-shaped admicelles formed upon the surface of Fe3O4@SiO2 NPs. Fe3O4@SiO2 NPs surface area reduced considerably from 88.74 to 60.82 m2 g−1, which verified large aggregations formed on the surface of Fe3O4@SiO2 NPs. Hydrophobic interaction helped phenanthrene (as a representative of hydrophobic substance) to be adsolubilized in PVP admicelles. The equilibrium adsorption capacity of PVP modified Fe3O4@SiO2 NPs for phenanthrene was 18.84 mg g−1, 2.01 times as that of Fe3O4@SiO2 NPs.

In this study, the effect of particle size on in vitro and in vivo behavior of astilbin nanosuspensions (AT-NSs) was investigated. AT-NSs with three different particle sizes (215.17 ± 4.83 nm, 496.51 ± 12.94 nm, and 803.34 ± 9.06 nm) were prepared using a simplified wet media milling technique by adjusting milling time. SEM and XRPD results showed that the three AT-NSs had similar appearance and crystalline state. The dissolution of AT-NSs was particle size dependent and in an order of 215.17 nm > 496.51 nm > 803.34 nm, however the AUC0–∞ of pharmacokinetics was in an order of 496.51 nm > 803.34 nm > 215.17 nm. AT-NSs with a larger particle size showed a higher accumulation in lung and liver because of reticuloendothelial system (RES). In conclusion, particle size had obvious impact on dissolution, pharmacokinetics and tissue distribution of AT-NSs, and the optimal particle size was 496.51 nm for the oral administration of AT-NSs.

The present study was performed to investigate the influence of ultrasound exposure on liver distribution and hepatoprotective effect of herpetrione nanosuspension (HPE NS) via oral administration. HPE NS was prepared by nanoprecipitation method and then characterized by particle size analysis, TEM, SEM and XRD. The pharmacokinetics and liver distribution of HPE NS after oral administration with the ultrasound exposure were evaluated and the protective effect of HPE NS against acute liver injury induced by CCl4 was also evaluated in a rat model. HPE NS with particle size of 213 ± 18 nm was successful prepared using nanoprecipitation method (bottom-up) by solvent–antisolvent addition. The images of TEM and SEM showed HPE NS were regular round shape with uniform and narrow size distribution. Results of XRD showed that HPE was amorphous state in both coarse powder and nanosuspension. In the in vivo pharmacokinetics and liver distribution studies in rats, ultrasound exposure had no influence on the pharmacokinetic characteristics of HPE NS after oral administration, but significantly increased the liver distribution of HPE NS. As evidenced by the lowering serum levels of ALT and AST and mitigating pathological lesions, the oral administration of HPE NS with the ultrasound exposure showed a superior hepatoprotective effect against CCl4 induced acute liver injury in rats as compared to oral administration of HPE NS without ultrasound exposure. These results revealed that ultrasound exposure could increase the liver distribution of HPE NS via oral delivery and ameliorate its hepatoprotective effect against CCl4 induced acute liver injury.

Fufang Biejia Ruangan Tablet (FBRT) is widely used for the treatment of liver fibrosis. However,Rats were subcutaneously injected with CClN-FBRT and FBRT could ameliorate CClSP 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-β1/Smad signaling pathway.

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.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 releaseThe 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 (These results suggested GL could be a potential carrier for the oral delivery of Pae.

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.

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 an...

In this study, the effect of particle size on skin permeation and retention of nitrofurazone (NTZ) from nanoparticle-loaded gels (NP-gels) was investigated to identify the suitable particle size of NTZ nanoparticle for topical delivery in order to achieve high deposition and low permeation of NTZ in the skin. NTZ nanosuspensions (NTZ-NSs) with three different particle size (299, 611, 906 nm) were prepared using wet media milling technique by adjusting milling speed and milling time, and then incorporated in carbopol gels for topical application. SEM and XRPD results showed that NTZ nanoparticles were well encapsulated in the gels network. The dissolution and the skin permeation of NTZ from NP-gels were particle size dependent and in an order of 299 nm > 611 nm > 906 nm, however, the skin deposition was in the order of 611 nm > 299 nm > 906 nm. The results demonstrated that the skin permeation and retention of NTZ from NP-gels were particle size dependent and the optimal size range was around 611 nm for topical application.

The objective of this work was to prepare and evaluate fast dissolving sublingual films containing meloxicam nanocrystals (MLX-NS-FDSFs). Nanocrystals (NS) were utilized to allow for improved dissolution of the drug, whereas the films were used to shorten the onset of action via the sublingual route. Meloxicam nanocrystals (MLX-NS) were prepared by nanoprecipitation based on acid-base neutralization method and then encapsulated into the films by solvent casting method. The obtained FDSFs exhibited uniform thickness of 82 ± 8 μm and drug content of 7.38 ± 0.011 mg/film (4 cm2) and disintegrated rapidly in 23.08 ± 1.76 s. The MLX-NS-FDSFs with reconstituted particle size of 196.4 ± 6.3 nm showed faster dissolution rate in vitro than the MLX coarse suspension based films (MLX-CS-FDSFs). The SEM images and XRD indicated that MLX nanocrystals were highly dispersed into the films. After administrated to rats, Tmax of MLX was significantly shortened following sublingual administration of MLX-NS-FDSFs. The absorption of MLX from MLX-NS-FDSFs resulted in 3.00 fold increased in bioavailability as compared to MLX-CS-FDSFs and 4.34 times with reference to the MLX-CS. These results indicated that the NS-FDSFs could be a promising delivery system to enhance the dissolution and shorten the onset time of MLX.

The purpose of this study was to develop stable nitrofurazone nanosuspensions based gel (NTZ nanogel) suitable for topical delivery with a view to increase skin bioavailability. NTZ nanosuspension (NTZ-NS) was fabricated by wet media milling technique, optimized by Box–Behnken design and then suitably gelled for systematically characterization. In order to confirm the advantages of NTZ nanogel for dermal application, skin permeation and retention studies in vitro were performed in comparison with NTZ marketed gel by using Franz diffusion cells. SEM showed that NTZ-NS were rectangular in shape and still stably kept their particle size after suitably gelled by carbopol preparation. In vitro dissolution studies exhibited a significant enhancement in dissolution rate of the drug from nanogel (85.73%) in comparison to the NTZ marketed gel (70.55%) after 24 h. In vitro permeation studies indicated that the amount of NTZ permeated through skin of NTZ nanogel (220.89 μg/cm2) after 24 h was higher than NTZ marketed gel (61.30 μg/cm2), and NTZ nanogel increased the accumulative amount of NTZ in rats' skin 5.5 times than NTZ marketed gel. These results suggested that nanogel is eligible for the use as suitable nanomedicine for topical delivery of poorly soluble drugs such as NTZ.

The aim of this study was to develop hyperoside (Hyp) nanocrystals to enhance its dissolution rate, oral bioavailability and anti-HBV activity. Hyp nanocrystals were prepared using high pressure homogenization technique followed by lyophilization. A Box-Behnken design approach was employed for process optimization. The physicochemical properties, pharmacokinetics and anti-HBV activity in vivo of Hyp nanocrystal prepared with the optimized formulation were systematically investigated. Hyp nanocrystals prepared with the optimized formulation was found to be rod shaped with particle size of 384 ± 21 nm and PDI of 0.172 ± 0.027. XRPD studies suggested slight crystalline change in drug. Dissolution rate obtained from Hyp nanocrystals were markedly higher than pure Hyp. The nanocrystals exhibited enhanced Cmax (7.42 ± 0.73 versus 3.80 ± 0.66 mg/L) and AUC0 - t (193.61 ± 16.30 versus 91.92 ± 17.95 mg·h/L) with a 210.63% increase in relative bioavailability. Hyp nanocrystals exhibited significantly greater anti-HBV activity than Hyp. These results suggested that the developed nanocrystals formulation had a great potential as a viable approach to enhance the bioavailability of Hyp.

In our previous study, cetyltrimethylammonium bromide (CTAB) admicelles on polystyrene (PS) microspheres for the adsolubilization of phenanthrene had been developed. In this work, CTAB admicelles modified on magnetic PS nanocomposites was used as a novel adsorbent to facilitate magnetic separation. Magnetic PS (MPS) nanoparticles (NPs) were synthesized by miniemulsion polymerization, in which the emulsifier was polyvinylpyrrolidone (PVP) and an oil phase consisted of oleate-modified Fe3O4 NPs dispersed in octane and styrene as the monomer. MPS NPs and CTAB-modified MPS NPs were characterized using transmission electron microscopy (TEM), vibrating sample magnetometry (VSM), Brunauer–Emmet–Teller, and atomic force microscopy (AFM) analysis. The TEM results revealed that the MPS NPs had regularly spherical shape with an average diameter of 140 nm. The saturation magnetization (Ms) of MPS NPs and CTAB-modified MPS NPs were 49.04 and 32.52 emu·g−1, respectively. Unexpectedly, AFM images revealed that the large admicelles were formed on MPS NPs due to PVP, and the height of the aggregates was 64 nm, 5.3 times as much as that of the aggregates on the PS microsphere. For CTAB-modified MPS NPs, the height of the aggregates increased to 99.9 nm. Through CTAB modification, the specific surface area of the MPS NPs notably reduced from 2.36 to 1.06 m2 g−1, which indirectly verified that bigger CTAB admicelles were formed. Cation–π electron interaction enabled phenanthrene to be adsolubilized in CTAB admicelles on MPS NPs. The equilibrium adsorption capacity of the CTAB-modified MPS NPs for phenanthrene was 24.3 mg g−1, which was 1.7, 2.1, and 6.0 times higher than the amount of the MPS NPs, CTAB-modified and original PS microspheres, respectively.

This study aimed to investigate the effect of exterior calcium alginate coating on physical stability of liposomes against solidification stress caused by freeze-drying and spray-drying. Uncoated liposomes (ULs) were prepared by a thin-film dispersion method, and exterior coating was achieved through crosslinking by dispersing calcium ions-loaded liposomes into bulk sodium alginate solution. Calcium alginate-coated liposomes (CALs) prepared under optimum conditions showed a particle size of 354.21 ± 5.4 nm and entrapment efficiency of 81.12 ± 2.5% using paclitaxel as a model drug. CALs showed better structural integrity in simulated gastric and intestinal fluids than ULs. Both CALs and ULs were solidified by freeze-drying and spray-drying, and their ability to withstand the processing stress was evaluated. CALs showed better performance in maintaining structural stability and keeping drug from leakage than ULs. The entrapment efficiency of CALs was 67.5 ± 2.5%, which was much higher than that of 36.4% of ULs after reconstitution from freeze-drying samples; similarly, the entrapment efficiency of spray-dried CALs was 58.6 ± 3.3%, but 47.8 ± 2.8% for ULs. Particle size and morphology observation by transmission electron microscopy also proved better preservation of CALs than ULs. Taken together, calcium alginate coating could significantly enhance physical stability of liposomes against the processing stress of solidification by freeze-drying and spray-drying.

The objective of this study was to prepare nanostructured lipid carrier (NLC)-based topical gel of Ganoderma Triterpenoids (GTs) and evaluate their effects on frostbite treatment. GT-NLCs was prepared by the high pressure homogenization method and then characterized by morphology and analyses of particle size, zeta potential, entrapment efficiency (EE), and drug loading (DL). The NLCs was suitably gelled for skin permeation studies in vitro and pharmacodynamic evaluation in vivo, compared with the GT emulgel. The GT-NLC remained within the colloidal range and was uniformly dispersed after suitably gelled by carbopol preparation. Transmission electron microscopy (TEM) study showed GT-NLCs was spherical in shape. The EE (%) and DL (%) could reach up to (81.84 ± 0.60)% and (2.13 ± 0.12)%, respectively. The result of X-ray diffractograms (XRD) showed that GTs were in an amorphous state in the NLC-gel. In vitro permeation studies through rat skin indicated that the amount of GTs permeated through skin of GT-NLCs after 24 h was higher than that of GT emulsion, and GT-NLCs increased the accumulative amounts of GTs in epidermis 7.76 times greater than GT emulsion. GT-NLC-gel was found to possess superior therapeutic effect for frostbite, compared with the GT emulgel. The NLC based topical gel of GTs could improve -their therapeutic effect for frostbite.

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

Ethnopharmacological relevance Herpetospermum caudigerum (HCD) is traditionally used for the treatment of liver diseases, cholic diseases, and dyspepsia as a well-known Tibetan medicine in China. The present study was designed to investigate the hepatoprotective effect of HCD and ascertain its active ingredients and possible mechanism. Materials and methods Mice were orally administrated with different parts (seeds, testa and kernel) and fractions of HCD. The hepatoprotective activities of different parts (seeds, testa and kernel) and three fractions (petroleum ether fraction, ethyl acetate fraction and aqueous fraction) with different polarities of HCD and herpetrione (HPE) isolated from HCD were determined using a mouse model of CCl 4 -induced liver injury based on the analysis of serum ALT and AST activities and the changes of antioxidant parameters like malondialdehyde (MDA) content, glutathione (GSH) level, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the liver. Moreover, the chemical analysis of different parts and fractions of HCD was later analyzed by HPLC. Results Our results showed that the ethyl acetate fraction and HPE significantly alleviated liver injury as indicated by the decreased levels of serum ALT and AST and reduce the pathological tissue damage induced by CCl 4 . Moreover, they decreased the MDA content and increased the levels of SOD, GSH and GSH-Px. Chemical analysis indicated that the ethyl acetate fraction were rich in HPE. Conclusions The lignans extract of Herpetospermum caudigerum is effective for the prevention of CCl 4 -induced hepatic damage in mice and HPE may be partially responsible for the pharmacological effect of hepatoprotection. The hepatoprotective effect may be related to its free radical scavenging effect, inhibiting lipid peroxidation and increasing antioxidant activity.

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.

Cucurbitacin B (Cu B), a potent anti-cancer agent, suffers with the problems of water-insoluble, gastrointestinal side effects and non-specific toxicity via oral administration and drawbacks in patient's compliance and acceptance through injections. An integration of nanoscale carriers with mucoadhesive buccal films drug delivery system would resolve these issues effectively with greater therapeutic benefits and clinical significance. Thus, the drug loaded mucoadhesive buccal film was developed and characterized in this study and the carboxymethyl chitosan (CCS) was chosen as a bioadhesive polymer, glycerol was chosen as a plasticizer and phospholipid-bile salts-mixed micelles (PL-BS-MMs) was selected as the nanoscale carriers. The CCS-films containing Cu B loaded PL-SDC-MMs was evaluated for the mechanical properties, mucoadhesion properties, in vitro water-uptake, in vitro release and morphological properties, respectively. The optimal CCS-films containing Cu B loaded PL-SDC-MMs was easily reconstituted in a transparent and clear solution with spherical micelles in the submicron range. The in vivo study revealed a greater and more extended release of Cu B from nanoscale CCS-films compared to that from a conventional CCS films (C-CCS-films) and oral marketed tablet (Hulusupian). The absorption of Cu B from CCS-films containing Cu B loaded PL-SDC-MMs resulted in 2.69-fold increased in bioavailability as compared to conventional tablet formulation and 10.46 times with reference to the C-CCS-films formulation. Thus, this kind of mucoadhesive buccal film might be an alternative safe route for delivery of Cu B with better patient compliance and higher bioavailability for the treatments.

Qingyuan Lv,1 Xianyi Li,2 Baode Shen,1 He Xu,1 Chengying Shen,1 Ling Dai,1 Jinxia Bai,1 Hailong Yuan,1 Jin Han11Department of Pharmacy, 302 Military Hospital, 2Institute for Drug and Instrument Control, Health Department, General Logistics Department of People's Liberation Army, Beijing, People's Republic of ChinaAbstract: The aim of this study was to investigate the feasibility of using spray granulation as a drying method to convert phospholipid (PL)-sodium deoxycholate (SDC)-mixed micelles (MMs) containing a water-insoluble drug to a solid dosage form and to evaluate how drugs with significantly different physicochemical properties affect the spray granulation process and subsequent in vitro and in vivo processes. Cucurbitacin B (Cu B) and glycyrrhizin (GL) were used as the model drugs. After spray granulation, the dried Cu B-PL/SDC-MM powder was completely redispersible within 15 minutes in vitro. Meanwhile, the area under the curve during 24 hours (AUC0–24) and peak serum concentration from the dried powder were significantly (P

In this study, a novel orodispersible film (ODF) containing drug nanoparticles was developed with the goal of transforming drug nanosuspensions into a solid dosage form and enhancing oral bioavailability of drugs with poor water solubility. Nanosuspensions were prepared by high pressure homogenization and then transformed into ODF containing drug nanoparticles by mixing with hydroxypropyl methylcellulose solution containing microcrystalline cellulose, low substituted hydroxypropylcellulose and PEG-400 followed by film casting and drying. Herpetrione, a novel and potent antiviral agent with poor water solubility that extracted from Herpetospermum caudigerum, was chosen as a model drug and studied systematically. The uniformity of dosage units of the preparation was acceptable according to the criteria of Japanese Pharmacopoeia 15. The ODF was disintegrated in water within 30s with reconstituted nanosuspensions particle size of 280 ± 11 nm, which was similar to that of drug nanosuspensions, indicating a good redispersibility of the fast dissolving film. Result of X-ray diffraction showed that HPE in the ODF was in the amorphous state. In the in vitro dissolution test, the ODF containing HPE nanoparticles showed an increased dissolution velocity markedly. In the pharmacokinetics study in rats, compared to HPE coarse suspensions, the ODF containing HPE nanoparticles exhibited significant increase in AUC0-24h, Cmax and decrease in Tmax, MRT. The result revealed that the ODF containing drug nanoparticles may provide a potential opportunity in transforming drug nanosuspensions into a solid dosage form as well as enhancing the dissolution rate and oral bioavailability of poorly water-soluble drugs.

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.

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

The aim of this study was to evaluate the effect of therapeutic ultrasound (TUS) on dermal delivery and therapeutic effect for frostbite of nanogel containing triterpenoids isolated from Ganoderma lucidum (GLT).GLT nanosuspension (GLT-NS) was prepared by high pressure homogenization and then suitably gelled to obtain GLT nanogel. The effects of TUS on GLT releasing from GLT nanogel and GLT permeation through the excised rat abdominal skin were evaluated. Moreover, a comparative study was also undertaken between different treatments of frostbite in rats: topical application of GLT nanogel (alone), TUS (alone) and GLT nanogel + TUS (plus).In the in vitro release study, TUS has no influence on drug release from the nanogel. Results of the in vitro transdermal study indicated that TUS significantly increased the cumulative amount of GLT permeating across and into the skin and reduced the lag time in comparison with passive diffusion (without TUS). As evidenced by the significant increase of wound healing area and the improvement in frostbite, TUS applied with simultaneous treatment method could improve the therapeutic effect of the GLT nanogel for frostbite.The present study revealed that the TUS can be effectively used to actively enhance topical delivery of GLT from nanogel and improve the therapeutic effect for frostbite in rats.

Cucurbitacin B (Cu B), formulated in the phospholipid-bile salts-mixed micelles (PL-BS-MMs), was transformed into dry powders by solidification process. Solidification methods for this transformation included freeze-drying, spray-drying or vacuum-drying, and different grades of process parameters called conservative, moderate and aggressive have been used in each solidification method, respectively. Saccharides (mannose, trehalose and glucose), polyethylene glycol (PEG) and mucoadhesive water-soluble polymers (carrageenan, hydroxpropylmethylcellulose (HPMC) and gelatin) were selected as the stabilizer, respectively. The influence of different stabilizers on the redispersibility of solid Cu B-PL/SDC-MMs was systemically investigated, such as the redispersibility index (RDI). The results showed that there were significant differences in RDI from samples stabilized by different stabilizers. The solid Cu B-PL/SDC-MMs stabilized by mucoadhesive water-soluble polymers (carrageenan, HPMC and gelatin) have better redispersibility under different solidification approaches, compared with those samples stabilized by other stabilizers. The results indicated that the mucoadhesive water-soluble polymers could effectively counter various stresses from the solidification process and prevent the nanocrystal surface from agglomeration. The combined action between steric hindrance and increased viscosity appeared to effectively avoid irreversible particle aggregation.

Herpetospermum caudigerum (HCD) is traditionally used for the treatment of liver diseases, cholic diseases, and dyspepsia as a well-known Tibetan medicine in China. The present study was designed to investigate the hepatoprotective effect of HCD and ascertain its active ingredients and possible mechanism.Mice were orally administrated with different parts (seeds, testa and kernel) and fractions of HCD. The hepatoprotective activities of different parts (seeds, testa and kernel) and three fractions (petroleum ether fraction, ethyl acetate fraction and aqueous fraction) with different polarities of HCD and herpetrione (HPE) isolated from HCD were determined using a mouse model of CCl4-induced liver injury based on the analysis of serum ALT and AST activities and the changes of antioxidant parameters like malondialdehyde (MDA) content, glutathione (GSH) level, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the liver. Moreover, the chemical analysis of different parts and fractions of HCD was later analyzed by HPLC.Our results showed that the ethyl acetate fraction and HPE significantly alleviated liver injury as indicated by the decreased levels of serum ALT and AST and reduce the pathological tissue damage induced by CCl4. Moreover, they decreased the MDA content and increased the levels of SOD, GSH and GSH-Px. Chemical analysis indicated that the ethyl acetate fraction were rich in HPE.The lignans extract of Herpetospermum caudigerum is effective for the prevention of CCl4-induced hepatic damage in mice and HPE may be partially responsible for the pharmacological effect of hepatoprotection. The hepatoprotective effect may be related to its free radical scavenging effect, inhibiting lipid peroxidation and increasing antioxidant activity.

The purpose of this study was to formulate stable Ganoderma lucidum (GLT) nanogels suitable for topical delivery with a view to improve the therapeutic effect for frostbite.GLT nanosuspensions were formulated using the high-pressure homogenization technique and then suitably gelled for characterized. In order to confirm the advantages of GLT nanogel for dermal application, skin permeation studies in vitro and pharmacodynamic evaluation in vivo were studied and compared with GLT-carbopol gel.The particle size analysis and SEM studies revealed that GLT nanosuspensions were still stably kept their particle size after suitably gelled by carbopol preparation. The drug content, pH, and spreadability of the GLT nanogel was found to be 99.23 ± 1.8%, 6.07 ± 0.1, and 26.42 (g·cm)/s, which were within acceptable limits. In vitro permeation studies through rat skin indicated that the amount of GLT permeated through skin of GLT nanogel after 24 h was higher than GLT-carbopol gel, and GLT nanogel increased the accumulative amount of GLT in epidermis five times than GLT-carbopol gel. No oedema and erythema were observed after administration of GLT nanogel on the rabbits' skin. Pharmacodynamic study showed that GLT nanogel was more effective than GLT-carbopol gel in treatment of frostbite.The GLT nanogel possess superior therapeutic effect for frostbite compared with the GLT-carbopol gel, which indicates that nanogels are eligible for the use as a suitable nanomedicine for dermal delivery of poorly soluble drugs such as GLT.

The purpose of this study was to design and optimize a novel drug nanoparticles-loaded oral fast dissolving film (NP-OFDF) using Box-Behnken design-response surface methodology.Drug nanosuspensions produced from high pressure homogenization were transformed into oral fast dissolving film containing drug nanoparticles by casting methods. Herpetrione (HPE), a novel and potent antiviral agent with poor water solubility that was extracted from Herpetospermum caudigerum, was studied as the model drug. The formulations of oral fast dissolving film containing HPE nanoparticles (HPE-NP-OFDF) were optimized by employing Box-Behnken design-response surface methodology and then systematically characterized.The optimized HPE-NP-OFDF was disintegrated in water within 20 s with reconstituted nanosuspensions particle size of 299.31 nm. Scanning electron microscopy (SEM) images showed that well-dispersed HPE nanoparticles with slight adhesion to each other were exposed on the surface of film or embedded in film. The X-ray diffractogram (XRD) analysis suggested that HPE in the HPE-NP-OFDF was in the amorphous state. In-vitro release study, approximate 77.23% of HPE was released from the HPE-NP-OFDF within 5 min, which was more than eight times compared with that of HPE raw materials (9.57%).The optimized HPE-NP-OFDF exhibits much faster drug release rates compared to HPE raw material, which indicated that this novel NP-OFDF may provide a potential opportunity for oral delivery of drugs with poor water solubility.