Fabrication and antibacterial evaluation of peppermint oil-loaded composite microcapsules by chitosan-decorated silica nanoparticles stabilized Pickering emulsion templating.

Novel peppermint oil (PO)-loaded composite microcapsules (CM) with hydroxypropyl methyl cellulose (HPMC)/chitosan/silica shells were effectively fabricated by PO Pickering emulsion, which were stabilized with chitosan-decorated silica nanoparticles (CSN). The surface modification of chitosan could improve the hydrophobicity of silica nanoparticles and favor their adsorption at the oil-water interface of PO Pickering emulsions. The microcapsule composite shells were formed dependent on the electrostatic adsorption of HPMC and CSN, and further subjected to spray-drying. The peppermint oil-loaded composite microcapsules with 100% HPMC as wall material (PO-CM@100%HPMC) seemed to be optimum formulation based on the prolonged release, acceptable entrapment efficiency (89.1%) and drug loading (25.5%). The PO-CM@100%HPMC could remarkably prolong the stability of PO. Moreover, the PO-CM@100%HPMC had a long-term antimicrobial activity (85.4%) against S. aureus and E. coli even after storage for 60 days. Therefore, the Pickering emulsions based microcapsules seemed to be a promising strategy for antibacterial application for PO.

Cellulose nanocrystals based clove oil Pickering emulsion for enhanced antibacterial activity.

An effective antibacterial system was developed by using clove essential oil Pickering emulsion (CO-PE). The carboxymethyl cellulose sodium modified cellulose nanocrystals (CNC) was used as the stabilizer of CO-PE, which were prepared by environmentally friendly approach of homogenization technology. The factors affecting the formation and stability of CO-PE were studied, such as CNC concentration, homogenization pressure, CO concentration and ionic concentration and pH. And the antibacterial performance of CO-PE against E. coli and S. aureus was investigated by determining the minimal inhibitory concentration (MIC). The results showed that 1% CNC stabilized CO-PE exhibited small droplet size and rough surface, and had good stability at high pH values or salt concentration, owing to the presence of CNC on interface of droplet. And the CNC-stabilized CO-PE exhibited higher antimicrobial activity at equivalent CO concentration, which might be attributed to efficiently adhere to bacterial membrane. Therefore, our research would provide new insights for antibacterial application of Pickering emulsions loading essential oils in the food and other industries.

Roles of maltodextrin and inulin as matrix formers on particle performance of inhalable drug nanocrystal-embedded microparticles.

The objective of this study was to investigate the influence of inulin (IL) and maltodextrin (MD) as matrix formers on the physical properties of drug nanocrystal-embedded microparticles (NEM) during spray-drying and storage. The redispersibility, aerodynamic performance and phase behaviour of NEM/MD and NEM/IL stored at different water activity (aw) values were evaluated. NEM with 2 g/g (relative to the weight of drug) of IL and MD exhibited the excellent performance after spray-drying. The water activity significantly influenced the redispersibility and aerodynamic performance of NEM/MD and NEM/IL. The NEM/MD presented a higher Tg at all aw values than did NEM/IL. The moisture-induced collapse of the amorphous glassy matrix of IL and MD could be responsible for the poor redispersibility and aerodynamic performance of NEM/IL and NEM/MD, respectively. The NEM/MD exhibited better aerodynamic performance at high aw (0.528) than did NEM/IL. Therefore, MD could be an excellent matrix former for inhalable NEM.

Comprehensive analyses of ZFP gene family and characterization of expression profiles during plant hormone response in cotton.

BACKGROUND: Zinc finger proteins (ZFPs) containing only a single zinc finger domain play important roles in the regulation of plant growth and development, as well as in biotic and abiotic stress responses. To date, the evolutionary history and functions of the ZFP gene family have not been identified in cotton. RESULTS: In this paper, we identified 29 ZFP genes in Gossypium hirsutum. This gene family was divided into seven subfamilies, 22 of which were distributed over 17 chromosomes. Bioinformatic analysis revealed that 20 GhZFP genes originated from whole genome duplications and two originated from dispersed duplication events, indicating that whole genome duplication is the main force in the expansion of the GhZFP gene family. Most GhZFP8 subfamily genes, except for GhZFP8-3, were highly expressed during fiber cell growth, and were induced by brassinosteroids in vitro. Furthermore, we found that a large number of GhZFP genes contained gibberellic acid responsive elements, auxin responsive elements, and E-box elements in their promoter regions. Exogenous application of these hormones significantly stimulated the expression of these genes. CONCLUSIONS: Our findings reveal that GhZFP8 genes are involved in cotton fiber development and widely induced by auxin, gibberellin and BR, which provides a foundation for the identification of more downstream genes with potential roles in phytohormone stimuli, and a basis for breeding better cotton varieties in the future.

Redispersible Pickering emulsion powder stabilized by nanocrystalline cellulose combining with cellulosic derivatives.

The objective of this study is to use cellulose nanocrystals (CNC) combining with carboxymethyl cellulose sodium (CMC-Na) and hydroxypropyl methylcellulose (HPMC) as stabilizer to prepare novel redispersible camellia oil Pickering emulsions powder (CO-PEP). Cellulose nanocrystals modified with carboxymethyl cellulose sodium (CNCC) was prepared by homogenization technology. CNCC seemed to be rod-like particles with mean particle size of 124.2 ± 2.5 nm. And the cellulose structure, crystal state and thermal property of CNCC remained unchanged during the homogenization. The combination of CNC and CMC-Na in CNCC might be dependent of physical interaction. The mean particle size of optimum CO-PE/0.25%CNCC was 0.569 ± 0.023 µm. The CNCC based particle stabilizer might form the distinctive barrier layer around oil droplet. The redispersibility results demonstrated that 50% HPMC based CO-PEP formed large composite particle with high drug loading ability and exhibited superior redispersibility. Novel redispersible powdered Pickering emulsions could be prepared by cellulose nanocrystals combining with water-soluble cellulosic derivatives.

Novel redispersible nanosuspensions stabilized by co-processed nanocrystalline cellulose-sodium carboxymethyl starch for enhancing dissolution and oral bioavailability of baicalin.

BACKGROUND: To improve the dissolution and bioavailability of poorly soluble drugs, novel nanosuspensions using co-processed nanocrystalline cellulose-sodium carboxymethyl starch (NCCS) as a synergetic stabilizer were first designed. METHODS: Co-processed NCCS was prepared by means of homogenization. Poorly soluble baicalin (BCA) was used as a model drug. BCA nanosuspension (BCA-NS/NCCS) using co-processed NCCS as a dispersant was prepared via homogenization and further converted into the dried BCA nanosuspension particle (BCA-NP/NCCS) via spray drying. The influence of NCCS on the dispersion efficiency of BCA-NS/NCCS was investigated. Morphology and crystal characteristic of NCCS and BCA-NP were analyzed. The dissolution and bioavailability evaluation were performed to investigate the feasibility of NCCS as a stabilizer for BCA-NS/NCCS and BCA-NP. RESULTS: The optimum 50% concentration of NCCS (nanocrystalline cellulose [NCC]:sodium carboxymethyl starch [SCS]=60:40) could be mostly beneficial for formation and stability of BCA-NS/NCCS. NCCS could completely prevent aggregation of BCA-NP during spray drying and enhance the redispersibility as well as dissolution of spray-dried BCA-NP, which might be attributed to "brick-concrete"-based barrier effect of NCCS and the swelling capacity of superdisintegrant SCS. The crystal state of NCC and BCA presented in BCA-NP/NCCS remained unchanged during the homogenization. The BCA-NP/NCCS exhibited a fast dissolution rate and significantly enhanced bioavailability of BCA. The AUC(0-∞) of the BCA-NP/NCCS (8,773.38±718.18 µg/L·h) was 2.01 times (P<0.05) as high as that of the crude BCA (4,354.61±451.28 µg/L·h). CONCLUSION: This study demonstrated that novel surfactant-free nanosuspensions could be prepared using co-processed NCCS as a synergetic stabilizer and also provided a feasible strategy to improve the dissolution and oral bioavailability of poorly soluble drug.

Novel breviscapine nanocrystals modified by panax notoginseng saponins for enhancing bioavailability and synergistic anti-platelet aggregation effect.

Breviscapine (BVP) is a flavonoid compound with strong neuroprotective and anti-platelet aggregation effect. The objective of this study is to design novel BVP nanocrystals modified by natural panax notoginseng saponins (PNS) for enhancing dissolution and anti-platelet aggregation effect of BVP. BVP nanocrystals modified by PNS (BVP-NC/PNS) were firstly prepared by coupling homogenization technology and freeze-drying technology, and BVP nanocrystals modified by RH40 (BVP-NC/RH40) as reference for comparison. The morphology, crystals characterization, dissolution behavior and anti-platelet aggregation effect of BVP-NC/PNS was systemically evaluated. The results demonstrated that the PNS could effectively maintain stability of BVP-NC at suspensions state dependent of its surface activity and the electrostatic repulsion effect. Combination of PNS and trehalose could prevent the aggregation of BVP-NC/PNS during freeze-drying. The PXRD and DSC results demonstrated that the BVP crystal state in BVP-NC/PNS was not changed owing to PNS modification and homogenization treatment. And the freeze-dried BVP-NC could easily recover back to BVP-NS and significantly improve the dissolution of BVP. The AUC(0-∞) of the BVP-NC/PNS was 4.54 times as high as that of the coarse BVP, but not significantly different compared to that of BVP-NC/RH40 (p < 0.05). The anti-platelet aggregation results demonstrated that, BVP-NC/PNS group showed more effective inhibition on PAF-induced platelet aggregation compared with corresponding control groups, which might attribute to the enhanced bioavailability of BVP and synergistic effect of PNS with BVP. In conclusion, PNS could be used as an alternative stabilizer for preparation of BVP-NC, and BVP-NC modified by PNS is a promising formulation strategy for enhancing oral bioavailability and anti-platelet aggregation of BVP.

Hyaluronic acid based nanocrystals hydrogels for enhanced topical delivery of drug: A case study.

The objective of this study is to use a carbohydrate polymer hyaluronic acid (HLA) as matrix to design novel transdermal nanogel loading poorly soluble drug nanocrystals. Baicalin nanocrystals (BCA-NC) were prepared by coupling homogenization technology and spray-drying technology. The morphology, the rheological behavior and transdermal permeation studies of HLA based BCA-NC-gel were evaluated. The results demonstrated that the BCA-NC could be successfully prepared in terms of trehalose after spray-drying. The trehalose could prevent the aggregation of BCA-NC during spray-drying. It was discovered that, the BCA-NC-gel with 1% HLA possessed the favorable gelatin capacity and thinning shear rheological property. In vitro transdermal permeation studies of BCA-NC-gel/HLA studies indicated a marked increase in the skin permeation of BCA. And the transdermal flux of BCA-NC-gel with 1% HLA were 20.65-fold higher (p < 0.01) than that of coarse BCA-gel, which could be attributed to particles size reduction of BCA-NC and bioadhesive property of HLA. And the morphology characterization of BCA-NC-gel/HLA demonstrated that BCA-NC could be imprisoned into the gel network of HLA, which might prevent it from aggregation in gel. In conclusion, HLA based nanogel system is a promising carrier for effectively transdermal delivery of poorly soluble drug.

Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide.

OBJECTIVE: The current study sought to design a quickly dissolving, high drug loading nanocrystal-based solid dispersion (NC-SD) in order to improve the dissolution of poorly soluble drugs. METHODS: The NC-SD was prepared by means of combination of homogenization and spray-drying. Polymer hydroxypropylmethylcellulose (HPMC) was used as baseline dispersant for NC-SD of the model drug - andrographolide (AG). Three superdisintegrants cohomogenized with HPMC were used as codispersant for AG-NC-SD and compared to common water-soluble dispersants - mannitol and lactose. The dissolution characterization and oral bioavailability of AG-NC-SD were evaluated. RESULTS: The AG-NC-SD with the higher concentration of HPMC exhibited fast dissolution due to the enhanced wettability of HPMC. The water-soluble codispersants (mannitol and lactose) did not completely prevent AG-NC from aggregation during spray-drying. To achieve much faster AG release, cohomogenized superdisintegrants at a level of 20% must be used along with 25% HPMC. Compared with water-soluble dispersants like mannitol and lactose, superdisintegrants with high swelling capacity were much more effective dispersants for enhancing fast redispersion/dissolution of AG-NC-SD via a swelling-triggered erosion/disintegration mechanism. Surfactant-free AG-NC-SD with 15% cohomogenized sodium carboxymethyl starch combined with 15% HPMC and 10% lactose enhanced the dissolution further, without comprising drug loading, exhibited a barely compromised dissolution rate compared to precursor NC suspensions (f2>50), and possessed drug loading up to 67.83%±1.26%. The pharmacokinetics results also demonstrated that the AG-NC-SD significantly improved the bioavailability in vivo of AG (P<0.05), compared with to the coarse AG. CONCLUSION: This study illustrates that a quickly dissolving, high drug load, surfactant-free NC-SD can be prepared by using a superdisintegrant as codispersant, and provides a feasible strategy to improve the oral bioavailability of poorly soluble drugs.

The Shielding Effect of Microcrystalline Cellulose on Drug Nanocrystal Particles During Compaction.

To elucidate the compaction behavior of drug nanocrystals based composite particles (NP) during tabletting, the compaction behavior of binary mixtures of microcrystalline cellulose (MCC) and nanocrystal particles was investigated. The force-displacement correlation of mixtures containing different ratios of MCC and micronized NP was studied in order to explain the nature on densification of NP during compaction, and the resultant compaction curves (pressure as function of in-die thickness) were systemically analyzed to elucidate the most important mechanisms of volume reduction for MCC and NP in different stages of compaction. The results showed that the close compaction of individual MCC was relatively quickly achieved, and the drug NP particles could slide into the intrinsic void spaces between MCC microparticles. This was the reason that the particles size of MCC used in this study was significantly larger compared to that of drug NP. This interstitial rearrangement phenomenon of NP occurred on a typical time scale and was strongly dependent on the speed of compaction. This migration behavior occurred on void spaces of MCC inter-particles might be identified as an elastic stress relaxation mechanism and be helpful to dissolution of NP. MCC can effectively shield the NP from significant aggregation during compaction process.

Apolipoproteins adsorption and brain-targeting evaluation of baicalin nanocrystals modified by combination of Tween80 and TPGS.

To help baicalin pass across BBB and improve its targeting in brain, we designed a novel formulation strategy of baicalin nanocrystals that preferentially adsorbing apolipoprotein E (ApoE) and repelling protein adsorption of opsonins. Intravenous baicalin nanocrystals suspensions (BCL-NS) modified by different surfactant were prepared by high-pressure homogenization. The targeting potential of surface-modified BCL-NS with mean particles size of about 250nm was assessed by in vitro protein adsorption studies using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), and further evaluated in vivo pharmacokinetics. The protein adsorption results showed that BCL-NS/TPGS, BCL-NS/TW80 and BCL-NS/TPGS+TW80 adsorbed very high amounts of apolipoproteins (ApoA-I, ApoA-Ⅱ, ApoA-IV, ApoC-III, ApoE, ApoJ) and relative low amounts of opsonins (fibrinogen, immunoglobulin heavy chain gamma, immunoglobulin light chain). The pharmacokinetics results demonstrated the AUC (0-∞) in brain of the BCL-NS/TW80+TPGS was 6.67 times as high as that of the BCL solution, and 2.59 times as high as that of the BCL-NS/TW80. It could be attributed to the most ApoE and Apo J adsorption indicative of strong BBB penetration, and least IgG γ and fibrinogen loading minimizing the risk of hepatic uptake. Combination of TW80 and TPGS can be rational choice of surfactants of baicalin nanocrystals for brain-targeting mediated by ApoE adsorption.

Hydroxypropylcellulose as matrix carrier for novel cage-like microparticles prepared by spray-freeze-drying technology.

The objective of this study is to design novel dissolution-enhanced microparticles loaded poorly soluble drug nanocrystals used a low viscosity of hydroxypropylcellulose (HPC) as matrix carrier. An interesting approach combined homogenization and the spray-freeze-drying technique was developed. The results demonstrated that the ratio of HPC to drug played an important role in size-reduction efficiency of drug during homogenization. And the formation of cage-like structure of the composite particles depended on ratio of HPC to drug. The spray-freeze-dried composite particles with HPC ratio of 1:2, 1:1 and 2:1 possessed excellent redispersibility, which attributed to its porous matrix and large surface area (3000m2/g). The dissolution of spray-freeze-dried composite particles with higher ratios of HPC (1:2 and 1:1) was significantly enhanced, which attributed to the particle size reduction of drug. The HPC could immobilize drug nanocrystals in its cage-like structure and prevent it from the subsequent agglomeration during storage. In conclusion, the prepared cage-like microparticles is a promising basis for further formulation development.

Design and Evaluation of Novel Solid Self-Nanodispersion Delivery System for Andrographolide.

Poorly water-soluble drugs offer challenges in developing a formulation product with adequate bioavailability. This study took advantage of the features of nanocrystals and direct compression technologies to develop a novel solid self-nanodispersion delivery system for andrographolide (Andro) in order to increase its dissolution rate for enhancing bioavailability. Andro nanosuspensions (Andro-NS) with a particle size of about 500 nm were prepared by homogenization technology and further converted into dried nanocrystal particles (Andro-NP) via spray-drying. The solid self-nanodispersion delivery system (Andro-SNDS)-loaded Andro-NP was prepared via direct compression technology. The DSC and PXRD results demonstrated that the Andro nanocrystals retained its original crystallinity. The dissolution of the Andro-SNDS formulation was 85.87% in pure water over 30 min, better than those of the coarse Andro and physical mixture of Andro and stabilizer. And the C max (299.32 ± 78.54 ng/mL) and AUC0-∞ (4440.55 ± 764.13 mg/L · h) of the Andro-SNDS formulation were significantly higher (p < 0.05) than those of the crude Andro (77.52 ± 31.73 ng/mL and 1437.79 ± 354.25 mg/L · h). The AUC of the Andro-SNDS was 3.09 times as high as that of the crude Andro. This study illustrated a novel approach to combine the features of nanocrystals and composite particles used to improve oral bioavailability of poorly soluble drug.

Panax Notoginseng Saponins as a Novel Nature Stabilizer for Poorly Soluble Drug Nanocrystals: A Case Study with Baicalein.

This study is aimed at seeking a nature saponin-based stabilizer for drug nanosuspensions. A poorly soluble drug (baicalein, BCL) was used as a model drug. BCL nanosuspensions with particle size of 156 nm were prepared by means of homogenization and converted into BCL nanocrystals (BCL-NC) stabilized with panax notoginseng saponins (PNS). It was found that PNS was able to prevent the aggregation of BCL-NS during storage and improve the redispersibility of BCL-NC after freeze-drying and spray-drying, compared with polymer stabilizer PVPK30. The freeze-dried and spray-dried BCL-NC with PNS exhibited excellent performance as evidenced by scanning_electron_microscope (SEM) analysis. It was the reason that PNS possessed the interfacial property (41.69 ± 0.32 mN/m) and electrostatic effect (-40.1 ± 1.6 mV), which could easily adsorb onto the surface of hydrophobic BCL nanocrystals and prevent from its aggregation. It is concluded that PNS can be used as an effective nature stabilizer for production of drug nanocrystals.

Roles of cryo/thermal strength for redispersibility of drug nanocrystals: a representative study with andrographolide.

Due to limited understanding about the effect of cryo/thermal strength from drying process on the redispersibility of drug nanocrystals, the impact of the different type and concentration of stabilizers and matrix formers on the redispersibility of nanocrystals were systematically investigated. Andro nanosuspensions were transformed into Andro nanocrystals (Andro-NC) via different drying process. The results demonstrated that the redispersibility of Andro-NC at the aggressive cryo-strength (meant higher freezing rate) was more excellent than those at conservative and moderate condition. Compared to the thermal stress from drying, the employed amount and type of stabilizers more dramatically affected the redispersibility of Andro-NCP during lyophilization. The HPMC-sucrose and HPMC-sorbitol system achieved excellent performance that protected Andro-NC from crystal growth during lyophilization. During spray-drying, the impacts of types and amounts of stabilizers on the redispersibility of Andro-NCP were more significant compared to those induced by the thermal stress conditions. The polymers HPMC, PVPK30 and MCCS with high Tg played an outstanding role in preventing the Andro-NCP from breakage during spray-drying, due to the firmly steric barrier effect of polymeric stabilizers. It is concluded that Andro-NCP is subjected to agglomeration or crystal growth due to cryo/thermal stresses during drying. The polymeric stabilizers are more effective to protect Andro-NCP from the cryo/thermal damage during solidification process, which behaved strong surface adsorption and high glass transition property at different solidification stress.

Microcrystalline cellulose-carboxymethyl cellulose sodium as an effective dispersant for drug nanocrystals: A case study.

This study is aimed at seeking an alternative dispersant for spray drying of drug nanosuspensions. The ideal dispersant is not only able to prevent the agglomeration of drug nanocrystals in the suspension state, but also it is able to preserve redispersibility of drug nanocrystals after drying. An active pharmaceutical ingredient (API) was used as a model drug. API nanosuspensions were prepared by homogenization and converted into nanocrystals powder (API-NP) with microcrystalline cellulose-carboxymethyl cellulose sodium (MCCS) via spray drying. It was found that MCCS was able to prevent the aggregation of API-NP in the suspension state and the agglomeration during spray-drying process, possibility due to its high Zeta potential and steric barrier from network structure, and reduction of API size at nanoscale and incorporation into MCCS network structure did not affect the solid state of API as evidenced by DSC and XRD analysis. The spray-dried API-NP/MCCS powders exhibited excellent sphere-shape performance, and could easily redispersed to API-NC suspensions state. Dissolution of the spray-dried API-NP was distinctly superior to those of the crude powder and physical mixture, respectively. Within 30 min, approximate 85.87% of API was dissolved from the API-NP/MCCS. MCCS was demonstrated to be an effective dispersant for spray-dried drug nanocrystals and preservation of the nanocrystals associated with excellent redispersibility.

The Roles of Vitrification of Stabilizers/Matrix Formers for the Redispersibility of Drug Nanocrystals After Solidification: a Case Study.

To elucidate the roles of vitrification of stabilizers/matrix formers for the redispersibility of drug nanocrystal powder after solidification at storage stress, the influence of different drying methods and storage stresses on stability of drug nanocrystals was systemically investigated. A poorly soluble drug, baicalin, used as model drug was converted into baicalin nanocrystals (BCN-NC). The residual moisture contents of BCN-NC were applied at two different stress conditions defined as "conservative" (<1%) and "aggressive" (>1%), respectively. The influence of different stabilizers, matrix formers, and storage stresses on the redispersibility of BCN-NC powder was systemically investigated, respectively. The results showed that storage stresses had significantly influence the redispersibility of BCN-NC. Aggressive storage temperature and residual moisture could be unfavorable factors for stability of drug nanocrystals, due to the exacerbation of aggregation of BCN-NC induced by vitrification. It was demonstrated that vitrification of spray-dried BCN-NC was dependent on temperature and time. The polymeric stabilizers hydroxypropylmethylcellulose (HPMC) and sodium carboxymethyl starch (CMS-Na) with high glass transition temperature (T g) played more important role in protecting the BCN-NC from breakage during storage, compared to the surfactants Tween 80, D-α-tocopherol acid polyethylene glycol 1000 succinate (TPGS), or RH 40. Besides, the polyvinylpyrrolidone K30 (PVP K30) and lactose with high T g were effective matrix formers for preserving the redispersibility of BCN-NC. It was concluded that the vitrification transition of stabilizers/matrix formers could be responsible for aggregation of drug nanocrystals during storage, which was a time-dependent process. The suitable residual moisture contents (RMC) and T g were very important for preserving the stability of drug nanocrystals during storage.

Solidification drug nanosuspensions into nanocrystals by freeze-drying: a case study with ursodeoxycholic acid.

To elucidate the effect of solidification processes on the redispersibility of drug nanocrystals (NC) during freeze-drying, ursodeoxycholic acid (UDCA) nanosuspensions were transformed into UDCA-NC via different solidification process included freezing and lyophilization. The effect of different concentrations of stabilizers and cryoprotectants on redispersibility of UDCA-NC was investigated, respectively. The results showed that the redispersibility of UDCA-NC was RDI-20 °C < RDI-80 °C < RDI-196 °C during freezing, which indicated the redispersibility of UDCA-NC at the conventional temperature was better more than those at moderate and rigorous condition. Compared to the drying strengthen, the employed amount and type of stabilizers more dramatically affected the redispersibility of UDCA-NC during lyophilization. The hydroxypropylmethylcellulose and PVPK30 were effective to protect UDCA-NC from damage during lyophilization, which could homogeneously adsorb into the surface of NC to prevent from agglomerates. The sucrose and glucose achieved excellent performance that protected UDCA-NC from crystal growth during lyophilization, respectively. It was concluded that UDCA-NC was subjected to agglomeration during solidification transformation, and the degree of agglomeration suffered varied with the type and the amounts of stabilizers used, as well as different solidification conditions. The PVPK30-sucrose system was more effective to protect UDCA-NC from the damage during solidification process.

Combination of submicroemulsion and phospholipid complex for novel delivery of ursodeoxycholic acid.

The objective of this study was to prepare and characterize ursodeoxycholic acid submicron emulsion (UA-SME) loaded with ursodeoxycholic acid phytosomes (UA-PS) and optimize the process variables. A screening experiment with response surface methodology with Box-Behnken design (BBD) was used to optimize the process parameters of UA-SME. The blood concentrations of UA after oral administration of UA-SME and UA coarse drug were assayed. The optimum process conditions were finally obtained by using a desirability function. It was found that stirring velocity, homogenization pressure and homogenization cycles were the most important variables that affected the particles size, polydispersity index and entrapment efficiency of UA-SME. Results showed that the optimum stirring velocity, homogenization pressure and cycles were 16 000 rpm, 60 MPa and 10 cycles, respectively. The mean diameter, polydispersity index and entrapment efficiency of UA-SME were 251.9 nm, 0.241 and 74.36%, respectively. Pharmacokinetic parameters of UA and UA-SME in rats were Tmax 2.215 and 1.489 h, Cmax 0.0364 and 0.1562 µg/mL, AUC0-∞ 3.682 and 13.756 µg h/mL, respectively. The bioavailability of UA in rats was significantly different (p < 0.05) after oral administration of UA-SME compared to those of UA coarse drug. This was due to improvement of the hydrophilicity and lipophilic property of UA-SME.

[Pathogens of prostatitis and their drug resistance: an epidemiological survey].

OBJECTIVE: To investigate the epidemiological features of the pathogens responsible for prostatitis in the Changshu area, and offer some evidence for the clinical treatment of prostatitis. METHODS: This study included 2 306 cases of prostatitis that were all clinically confirmed and subjected to pathogenic examinations in 3 hospitals of Changshu area from 2008 to 2012. Neisseria gonorrhoeae, mycoplasma urealyticum and chlamydia trachomatis were detected by nucleic acid amplification ABI 7500, the bacterial data analyzed by VITEK-2 Compact, the drug-resistance to antibacterial agents determined using the WHONET 5.6 software, and the enumeration data processed by chi-square test and curvilinear regression analysis using SPSS 19.0. RESULTS: The main pathogens responsible for prostatitis were found to be Staphylococcus haemolyticus (30%), Staphylococcus epidermidis (12%), Enterococcus faecalis (9%), Escherichia coli (6%), Staphylococcus warneri and Staphylococcus aureus (3%), Mycoplasma urealyticum (8%), chlamydia trachomatis (5%) and Neisseria gonorrhoeae (6%). Statistically significant increases were observed in the detection rates of Escherichia coli (chi2 = 17.56, P<0.05), Mycoplasma urealyticum (chi2 = 8.73, P<0.05), Chlamydia trachomatis (chi2 = 8.73, P<0.05) and Enterococcus (chi2 = 8.22, P<0.05), but not in other pathogens. The resistance rates of Gram-positive bacteria to erythromycin and benzylpenicillin G were both above 45%, but with no significant difference between the two, those of Oxacillin (chi2 = 10.06, P<0.05) and Cefoxitin (chi2 = 9.89, P<0.05) were markedly increased, but those of quinolones, gentamycin and clindamycin remained low, except rifampicin (chi2 = 11.09, P<0.05). The resistance rates of Gram-negative bacteria to cefazolin and ampicillin were relatively high (mean 57.3%), and those to ceftriaxone (chi2 = 11.26, P<0.05) and trimethoprim sulfamethoxazole (chi2 =11.00, P< 0.05) significantly high; those to amikacin, cefepime, piperacillin/tazobactam and imipenem remained at low levels with no significant changes. However, the resistance rates of mycoplasma urealyticum to ciprofloxacin (chi2 = 11.18, P<0.05) and azithromycin (chi2 = 9.89, P<0.05) were remarkably increased. CONCLUSION: Gram-positive bacteria are the major pathogens responsible for prostatitis, but Escherichia coli, enterococcus and sexually transmitted disease pathogens are found to be involved in recent years. Quinolones and aminoglycosides are generally accepted as the main agents for the treatment of Gram-positive bacterial infection. However, rational medication for prostatitis should be based on the results of pathogen isolation and drug sensitivity tests in a specific area.