The correlation between CT features and insulin resistance levels in patients with T2DM complicated with primary pulmonary tuberculosis.

The aim is to investigate the correlation between computed tomography (CT) features and insulin resistance levels in patients with type 2 diabetes mellitus (T2DM) complicated with primary pulmonary tuberculosis (PTB). Nearly, 268 untreated PTB patients complicated with T2DM were divided into two groups according to the optimal cutoff value of HOMA-IR score for the Chinese population: HOMA-IR ≤ 2.69 (Group I: 74 patients), >2.69 (Group II: 194 patients). The basic characteristics and changes of CT manifestations were analyzed. In the two groups, the detection rate of large segmented leafy shadow was 39.2% and 78.9%; the air bronchogram sign detection rate was 40.5% and 80.9%; the discovery rate of mouth-eaten cavity was 33.8% and 73.7%; the thin-walled cavity detection rate was 2.7% and 16.0%; the rate of multiple cavities was 35.1% and 69.6%; and bronchial tuberculosis was found in 4.1% and 35.6%, respectively. The detection rates of lesions in Group II were significantly higher than in Group I (p < .05). HOMA-IR was found independently associated with large segmented leafy shadow, air bronchial sign, thin-walled cavity, and bronchial tuberculosis. The level of insulin resistance can effectively reflect the severity of PTB patients with T2DM. CT scan can directly provide image information in clinics. These two examinations can guide clinicians to accurately formulate subsequent treatment plans.

Effect of local chain deformability on the temperature-induced morphological transitions of polystyrene-b-poly(N-isopropylacrylamide) micelles in aqueous solution.

The effect of temperature on the micellar morphology of two polystyrene-b-poly(N-isopropylacrylamide) (PS-b-PNIPAM) diblock copolymers in an aqueous solution was investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). At 25 °C, a mixture of vesicles and spheres are observed for the micelles of PS65-b-PNIPAM108, while PS65-b-PNIPAM360 exhibits mixed cylindrical and spherical micellar morphology. Upon increasing the temperature, the micellar morphology becomes spherical for PS65-b-PNIPAM108 at 60 °C and for PS65-b-PNIPAM360 at 40 °C. Such vesicle-to-sphere and cylinder-to-sphere transitions of micellar morphology are reversible when the micellar solutions are cooled back to 25 °C. However, these temperature-induced morphological transitions of the PS-b-PNIPAM micelles are contrary to the theoretical prediction. Qualitative analysis of the free energy shows that vesicular or cylindrical micelles tend to form at higher temperatures if only the overall volume change of the PNIPAM block is considered. The contradiction between the experimental results and theoretical prediction is interpreted in terms of the local deformability of the PNIPAM chains. At elevated temperatures, the collapsed PNIPAM globules are less deformable and must occupy larger areas at the micellar interface, although the overall volume is smaller at higher temperatures. This will lead to a larger repulsion between the PNIPAM globules and a remarkable increase in the free energy of the corona; thus, the formation of vesicles or cylinders at higher temperatures is prohibited.

[Analysis of clinical features and early warning indicators of death from hand, foot and mouth disease in Shandong province].

OBJECTIVE: To understand the clinical features of death from hand, foot and mouth disease (HFMD) and to explore the early warning index of HFMD death. METHODS: A total of 41 HFMD death cases were collected as case group in Shandong province between 2009 and 2011, and another 123 serious HFMD cases were selected as control group according to the similar gender, place of origin and hospital level, with the ratio at 1:3. We investigated the general situation, clinical treatment, past medical history, clinical symptoms and signs of the ill children, and applied the conditional logistic regression to explore early warning index of HFMD death. RESULTS: The rate of patients who had symptoms in nervous system, digestive system, circulatory system and respiratory system were separately 90.2% (37/41), 58.5% (24/41), 53.7% (22/41) and 90.2% (37/41) in case group; and the proportions were 44.7% (55/123), 13.8% (17/123), 10.6% (13/123) and 12.2% (15/123) respectively in control group. The difference between the two groups showed statistical significance (χ(2) = 25.881, 32.791, 34.011, 86.505, P < 0.05). In case group, 37 patients had neurogenic pulmonary edema, 26 patients got encephalitis, 15 patients had respiratory and circulatory failure, 7 patients got pulmonary hemorrhage, 4 patients had multiple organ failure, 4 patients got myocarditis and 1 patient had cerebral hernia. According to multi-factor logistic regression analysis, the early warning indicators of HFMD death included neck resistance (case group: 34.1% (14/41), control group: 4.1% (5/123); OR = 7.145, 95%CI: 1.748 - 29.204), vomiting (case group: 58.5% (24/41), control group: 13.8% (17/123); OR = 5.632, 95%CI: 1.793 - 17.685) and increase of heart rate (case group: 53.7% (22/41), control group: 10.6% (14/123), OR = 6.370, 95%CI: 1.517 - 26.743). CONCLUSION: In the process of clinical treatment and care, we should interfere the serious HFMD patients with neck resistance, vomiting and increase of heart rate, and thereby reduce the death from HFMD.

Glucose production from hydrolysis of cellulose over a novel silica catalyst under hydrothermal conditions.

A novel silica catalyst was synthesized by evaporation-induced self-assembly (EISA) method and tested for the catalytic selective hydrolysis of cellulose to glucose. This silica catalyst exhibited a higher catalytic activity than other oxides prepared by the same method, such as ZrO2, TiO2, and Al2O3. Using silica as a catalyst, cellulose was selectively hydrolyzed into glucose with a glucose yield as high as 50% under hydrothermal conditions without hydrogen gas. The silica catalyst was characterized by Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD) and transmission electron microscopy (TEM). The results of temperature-programmed desorption of ammonia (NH3-TPD) and textural properties indicated that the synergistic effect between strong acidity and a suitable pore diameter of the silica catalyst may be responsible for its high activity. In addition, the catalyst was recyclable and showed excellent stability during the recycle catalytic runs.

Pneumomediastinum and subcutaneous emphysema secondary to dental extraction: Two case reports.

BACKGROUND: Dental extraction is a common operation in oral surgery and is usually accompanied by pain, swelling, and local infection. The application of high-speed air turbines increases the comfort of alveolar surgery and makes it more minimally-invasive. However, high-speed gas can enter the subcutaneous tissue of the face and neck or even the chest and mediastinum, which is a serious iatrogenic complication. CASE SUMMARY: We describe two cases of severe subcutaneous and mediastinal emphysema caused by high-speed turbine splitting during dental extraction. The first case involved a 34-year-old man who complained of swelling of the face, mild chest tightness, and chest pain after dental extraction. Computed tomography (CT) scan showed a large amount of gas in the neck, chest wall, and mediastinum. The second case involved a 54-year-old woman who complained of swelling and pain of the neck after dental extraction. CT showed a large amount of gas collected in the neck and mediastinum. Both of them used high-speed turbine splitting during dental extraction. CONCLUSION: High-speed turbine splitting during dental extraction may lead to severe subcutaneous and mediastinal emphysema. Dentists should carefully operate to avoid emphysema. If emphysema occurs, CT can be used to improve the diagnosis. The patient should be informed, and the complications dealt with carefully.

Concrescence of maxillary second molar and impacted third molar: A case report.

BACKGROUND: Morphological anomalies of teeth, including talon cusp, dens evaginatus, gemination, fusion, concrescence, root dilaceration, and taurodontism, always involve changes in the enamel, cementum and dentin. Diagnosing concrescent teeth through routine clinical examination alone is difficult, and most cases of concrescence are found accidentally during extraction. A definite preoperative diagnosis of concrescence would contribute to a better treatment plan and fewer undesirable complications. CASE SUMMARY: A 47-year-old woman who complained of left maxillary first molar loss for half a year presented to our department seeking treatment by dental implant restoration. Panoramic radiography and cone-beam computed tomography (CBCT) showed an unclear boundary between the distal root of the second molar and the mesial root of the third molar. The teeth were extracted under local anesthesia, and a definite diagnosis of concrescence was made by histopathological examination. CONCLUSION: CBCT is a useful tool for diagnosing and planning the management of tooth concrescence and may be beneficial for reducing unnecessary complications.

Porous quaternized chitosan nanoparticles containing paclitaxel nanocrystals improved therapeutic efficacy in non-small-cell lung cancer after oral administration.

Clinical application of paclitaxel (PTX) is limited because of its poor solubility in aqueous media. To overcome this hurdle, we devised an oral delivery system by encapsulating PTX into N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride (HTCC) nanoparticles. These nanoparticles were small (~130 nm), had a narrow size distribution, and displayed high loading efficiency owing to the homogeneous distribution of PTX nanocrystals. The matrix hydrophilicity and porous structure of the obtained nanoparticles accelerated their degradation and improved drug release. In vitro and in vivo transport experiments had proved that the presence of positive charges enhanced the intestinal permeability of these nanoparticles. Further in vitro experiment of cytotoxicity showed that the PTX-loaded HTCC nanoparticle (HTCC-NP:PTX) was more effective than native PTX owing to enhanced cellular uptake. Drug distribution in tissues and in vivo imaging studies confirmed the preferred accumulation of HTCC-NP:PTX in subcutaneous tumor tissue. Subsequent tumor xenograft assays demonstrated the promising therapeutic effect of HTCC-NP:PTX on inhibition of tumor growth and induction of apoptosis in tumor cells. Additional investigation into side effects revealed that HTCC-NP:PTX caused lower Cremophor EL-associated toxicities compared with Taxol. These results strongly supported the notion that HTCC nanoparticle (HTCC-NP) is a promising candidate as an oral carrier of PTX for cancer therapy.

Hyaluronic acid-based nanogels derived from multicomponent self-assembly for imaging-guided chemo-photodynamic cancer therapy.

Multifunctional theranostic nanoplatforms integrated of imaging function, multi-modality therapy, stimuli-responsiveness, and targeted delivery are of highly desirable attributes in achieving precise medicine. However, preparation of multifunctional nanoplatforms often involves laborious, multiple steps and inevitably utilizes low-biocompatible or non-functional components. Herein we report a facile, one-step self-assembly strategy to fabricate hyaluronic acid (HA)-based multifunctional tumor theranostic nanoplatform by employing magnetic resonance imaging (MRI) agent Mn2+ as a reversible crosslink agent for histidine-grafted HA, along with simultaneously loading chemotherapeutic agent doxorubicin hydrochloride (DOX) and photodynamic therapy agent chlorin e6, to realize MRI-guided targeted chemo-photodynamic cancer therapy. The targeted delivery and stimuli-responsive payload release were demonstrated in vitro and in vivo. Furthermore, the combined chemo-photodynamic therapy of the nanoassembly dramatically improved the cancer therapeutic outcome, in comparison with that of free DOX and nanoplatform solely loaded DOX in a melanoma bearing mice. Our one step assemble strategy is of great potential in clinic transformation.

In-Situ-Bloomed Micrometer-Scale Ultrathin Nanosheets in Tumor-Microenvironment for Intensive Photothermal-Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT), as the emerging modality of cancer therapy based on Fenton or Fenton-like reactions, still suffers from low efficacy of hydroxyl radical generation, which requires full exposure of reaction sites of CDT nanoagents to intracellular H2O2. However, the amount of exposed reaction sites is severely restrained by the controlled size (<200 nm) and the limited specific surface area of nanoagents. Herein, we highlight the in-situ bloomed micrometer-scale CoMn-based layered double hydroxide (CoMn-LDH) ultrathin nanosheets, which are derived from CoMn boride-based CMB@ss-SF nanospheres in response to overexpressed glutathione (GSH) and dissolved oxygen in tumor microenvironment (TME), accomplishing intensive photothermal-enhanced CDT. The micrometer-scale CoMn-LDH ultrathin nanosheets would provide abundant reactive sites to accelerate heterogeneous Fenton-like reaction as well as GSH depletion, eliciting quick release of metal ions and further realizing intensive homogeneous Fenton-like reactions for ·OH generation. Moreover, the nanoagent can harvest 808 nm light into heat, which can be utilized to promote the CDT efficacy and realize photoacoustic imaging (PAI). Because of acidity and overexpressed GSH in TME, the nanoagent exhibited superior biodegradability. Benefiting from the synergistic advantages, CMB@ss-SF with negligible cytotoxicity completely eradicated the tumors in mouse. This work provides avenue for developing CDT nanoagents.

[Preparation of ibuprofen/sPEG-b-PLLA copolymer microspheres and its in vitro release properties].

Biodegradable four-arm star-shaped poly(ethylene glycol)-block-poly(L-lactic acid) copolymer (sPEG-b-PLLA), four-arm star-shaped poly(L-lactic acid) (sPLLA), linearly poly(ethylene glycol)-block-poly(L-lactic acid) copolymer (PEG-b-PLLA) and linearly poly(L-lactic acid) (PLLA) were synthesized from L-lactice acid, pentaerythritol, poly(ethylene glycol) and star-shaped poly(ethylene glycol), using the method of melt polycondensation, and the products were characterized and confirmed by 1H NMR spectroscopy, FT-IR and GPC. Four types of ibuprofen loaded microspheres based on the above four types of polymers, i.e., IBU/PLLA, IBU/sPLLA, IBU/PEG-b-PLLA, and IBU/sPEG-b-PLLA microspheres were prepared using the method of solvent evaporation, and the optimized preparation technology was obtained via orthogonal experiments, and the drug-encapsulating properties and in vitro drug-releasing properties were studied. The results showed that compared with IBU/PLLA and IBU/PEG-b-PLLA microspheres, the drug encapsulate efficiency of IBU/sPLLA and IBU/sPEG-b-PLLA microspheres were higher and the in vitro drug releasing rate slowed down, which mainly due to the faster degradation of sPLLA and sPEG-b-PLLA for the star-shaped structure and the block copolymerization of sPEG. The drug releasing curves of these three types of microspheres could be fit by first-order equation, and the releasing mechanism was non-Fickian diffusing, i.e., the synergetic effect of polymer degradation and drug diffusion.

Antioxidant and Anti-Aging Activities of Ethyl Acetate Extract of the Coral Tooth Mushroom, Hericium coralloides (Agaricomycetes).

The in vitro antioxidant effects of petroleum ether, ethyl acetate, and ethanol extracts isolated from Hericium coralloides were investigated. Overall, the ethyl acetate extract of H. coralloides (HcEAE) showed better antioxidant activity in vitro than the petroleum ether and ethanol extracts (HcPEE and HcETE, respectively) of H. coralloides. A comprehensive investigation of the antioxidant activity of the HcEAE in vitro indicated that it possessed superior antioxidant activity, with half maximal inhibitory concentration (IC50) values of 0.93, 1.84, 1.59, and 0.6 mg/mL against DPPH, hydroxyl, ABTS+, and superoxide (O2- ) radicals, respectively. To assess in vivo antioxidant activity, three different doses of HcEAE were orally administered in a D-galactose-induced aged mouse model. Administration of HcEAE significantly increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and lowered the levels of malondialdehyde (MDA) in brains and sera of mice in a dose-dependent manner. A histopathology assessment indicated that the HcEAE could ameliorate the anile condition of the model mice. These results suggest that the HcEAE has potent antioxidant activity and could minimize the occurrence of age-associated disorders associated with free radicals.

Uniform-sized PLA nanoparticles: preparation by premix membrane emulsification.

Nanoparticle size is crucial to drug release behavior and biodistribution in vivo, but few studies have been performed on biodegradable nanoparticles with narrow size distribution. In this note, uniform-sized nanoparticles were prepared by a facile method combining emulsion-solvent removal and premix membrane emulsification for the first time. After preparation of coarse emulsions, additional premix membrane emulsification with very high pressure was occupied to achieve uniform-sized nanodroplets, and nanoparticles were formed by further solidification. Polylactide (PLA) was selected as a model polymer. Several factors played key roles to obtain uniform-sized PLA nanoparticles, including type of organic solvent, the volume ratio of oil phase and external water phase, pore size of the microporous membrane and transmembrane pressure. The coefficient of variation (CV) value of PLA nanoparticles could be controlled below 16.9% under an optimum condition. The novel method also has the advantages of high productivity, simplicity and easy scale-up. The uniform-sized nanoparticles prepared by this novel method have great potentials in drug delivery.

Preparation of uniform-sized PELA microspheres with high encapsulation efficiency of antigen by premix membrane emulsification.

Relatively uniform-sized poly(lactide-co-ethylene glycol) (PELA) microspheres with high encapsulation efficiency were prepared rapidly by a novel method combining emulsion-solvent extraction and premix membrane emulsification. Briefly, preparation of coarse double emulsions was followed by additional premix membrane emulsification, and antigen-loaded microspheres were obtained by further solidification. Under the optimum condition, the particle size was about 1 mum and the coefficient of variation (CV) value was 18.9%. Confocal laser scanning microscope and flow cytometer analysis showed that the inner droplets were small and evenly dispersed and the antigen was loaded uniformly in each microsphere when sonication technique was occupied to prepare primary emulsion. Distribution pattern of PEG segment played important role on the properties of microspheres. Compared with triblock copolymer PLA-PEG-PLA, the diblock copolymer PLA-mPEG yielded a more stable interfacial layer at the interface of oil and water phase, and thus was more suitable to stabilize primary emulsion and protect coalescence of inner droplets and external water phase, resulting in high encapsulation efficiency (90.4%). On the other hand, solidification rate determined the time for coalescence during microspheres fabrication, and thus affected encapsulation efficiency. Taken together, improving the polymer properties and solidification rate are considered as two effective strategies to yield high encapsulation.

[Synthesis, characterization and photoluminescence properties of (EuxRE1-x)(beta-NTA)3phen complexes].

Two series of solid complexes of EuxRE1-x(beta-NTA)3 phen (RE = Y3+ and Tb3+, x = 0.10, 0.30, 0.50, 0.70, 0.90) were synthesized in alcohol. They were characterized by elemental analysis, IR spectra, molar conductivity, 1H NMR spectra and TG-DTA. The molar conductivity indicated that all the complexes were nonelectrolyte; and 1H NMR spectra and IR spectra showed that the ligand coordinates(double-tooth) with RE3+ ions through the oxygen negative ion of enolic form of beta-NTA and the two nitrogen atoms of phen. The fluorescence properties of these complexes were studied, the results indicated that the chemical bonds have formed by the rare earth ions with the two ligands energy can be transferred from the ligand to the RE3+, and the excited spectra was very wide showing that energy transfer was efficient, the fluorescence emission intensity of 5 D0-->7 F2 transitions in the strongest according to the emission spectra of the complexes. So the authors choose this energy transition as the research object and the results showed that the emission intensity of Eu3+ ion can be enhanced if a part of Eu3+ ions were substituted by Y3+ or Tb3+ ions. But the concentration of the Y3+ or Tb3+ ions can influence the fluorescence emission intensity of the rare earth complexes. The authors changed the concentration of Y3+ and Tb3+ in order to find the proper proportion Finally the authors found that if the x < 0.3 for the complexes EuxY1-x (beta-NTA)3 phen can get higher fluorescence intensity than pure Eu3+ system, but compared with the concentration of Y3+, the proportion of Tb3+ is different. The result showed that if x < 0.5 the authors can get higher fluorescence intensity. In all, at a proper proportion of the doping ions (Y3+ or Tb3+) the authors can get higher fluorescence intensity. This doping method not only decreases the cost of materials, but also enhances the fluorescence intensity, so it has a bright future in practical application.

A systematic evaluation of the biocompatibility of cucurbit[7]uril in mice.

As one of the most water-soluble members in the macrocyclic cucurbit[n]uril (CB[n]) family, CB[7] has attracted increasing attention in pharmaceutical and biomedical fields. Despite extensive studies regarding the potential use of CB[7] for biomedical applications, its full safety and toxicity profile in a clinically relevant model is still lacking. Herein we report the full biocompatibility profile of CB[7], administered orally, peritoneally or intravenously in mice, respectively. Body-weight changes showed no significant differences among various groups of mice after they were administered with CB[7] at a single dose of 5 g/kg orally, 500 mg/kg peritoneally and 150 mg/kg intravenously, respectively. Hematology tests, as well as hepatic and renal function biochemical markers tests, of the blood collected from these mice sacrificed 21 days after CB[7] administration all exhibited normal ranges of values that were comparable with those of the control group. Moreover, histopathological analysis on the sections of major organs (including the heart, liver, spleen, lungs and kidneys) and gastrointestinal tissues revealed no detectable injuries and inflammatory cells infiltration. Taken together, these results suggest an excellent biocompatibility profile of CB[7] in mice, which provide important foundations for further investigations and even clinical applications of CB[7] in biomedical areas.

Macrocycle-wrapped polyethylenimine for gene delivery with reduced cytotoxicity.

Due to its outstanding capability to facilitate DNA condensation, transportation and endosomal escape, polyethylenimine (PEI) has been frequently studied for gene delivery. However, its molecular weight (M.W.) dependent transfection efficiency and cytotoxicity has severely limited its clinical application. To resolve this dilemma, a supramolecular strategy was developed for the first time, in which PEI with large M.W. (branched, 25 kDa) that has a satisfactory transfection efficiency, yet high non-specific cytotoxicity for gene delivery was wrapped with macrocyclic cucurbit[7]uril (CB[7]). The successful wrapping of the PEI by the macrocyclic CB[7] was proved by 1H NMR spectroscopy and supported by isothermal titration calorimetry (ITC). The plasmid DNA (pDNA) condensability of PEI was not affected by the supramolecular coating as evidenced from the agarose gel electrophoresis assay. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results demonstrated that the particle size, zeta potential, and morphology of the self-assemblies of PEI/pDNA and PEI/CB[7]/pDNA were comparable. As a consequence of the supramolecular wrapping, the cytotoxicity of PEI was significantly constrained as demonstrated by MTT assay, apoptosis assay, and a hemolysis study. In particular, both the cellular uptake and the gene transfection efficiency results suggest that the supramolecular wrapping of PEI by CB[7] exhibits negligible effects on PEI, thus functioning as an effective non-viral gene delivery vector. This novel supramolecular-wrapping strategy provides new insights for facile alleviation of the non-specific toxicity of PEI and potentially other polycationic gene vectors without compromising their transfection efficiency.

Polymeric Nanomedicine with "Lego" Surface Allowing Modular Functionalization and Drug Encapsulation.

Surface functionalization of nanoparticles (NPs) is of pivotal importance in nanomedicine. However, current strategies often require covalent conjugation that involves laborious design and synthesis. Herein, cucurbit[7]uril (CB[7])-decorated poly(lactic acid) (PLA)/poly(lactic-co-glycolic acid) (PLGA) NPs are developed and exploited for the first time as a novel, biocompatible, and versatile drug delivery platform with a noncovalently tailorable surface. CB[7] on the surface of NPs, acting as a "Lego" base block, allowed facile, modular surface modification with a variety of functional moieties or tags that are linked with amantadine (a complementary "Lego" piece to the base block), including amantadine-conjugated folate, polyethylene glycol, and fluorescein isothiocyanate. In addition, surface CB[7] also provided an opportunity for encapsulation of a secondary drug, such as oxaliplatin, into the cavity of the base block CB[7], in addition to a primary drug (e.g., paclitaxel) loaded into PLA/PLGA NPs, for a possible synergistic chemotherapy. This proof of concept not only provides the first versatile PLA/PLGA nanomedicine platform with "Lego" surface for modular functionalization and improved drug delivery but also offers new insights into the design and development of novel nanomedicine with a modular surface.

A thermosensitive hydrogel based on quaternized chitosan and poly(ethylene glycol) for nasal drug delivery system.

A new thermosensitive hydrogel was designed and prepared by simply mixing N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) and poly(ethylene glycol) (PEG) with a small amount of alpha-beta-glycerophosphate (alpha-beta-GP). The optimum preparative condition was investigated, and the obtained formulation underwent thermal transition from solution below or at room temperature to non-flowing hydrogel around 37 degrees C in several minutes. As a new formulation, its potential use as nasal drug delivery system was studied. It can be dropped or sprayed easily into nasal cavity and spread on the nasal mucosa in solution state. After being administered into nasal cavity, the solution transformed into viscous hydrogel at body temperature, which decreased nasal mucociliary clearance rate and released drug slowly. Morever, quaternized chitosan as absorption enhancer has been studied extensively in several reports and proved its non-toxicity, mucoadhesivity and the capacity to open the tight junctions between epithelial cells. Therefore, in this study insulin as a model drug was entrapped in this formulation and its release behavior in vitro was also investigated. The enhancement of absorption of fluorescein isothiocyanate (FITC)-labeled insulin in rat nasal cavity by this formulation was proved by confocal laser scanning microscopy (CLSM). The cytoxicity and the change of the blood glucose concentration after nasal administration of this hydrogel were also investigated. The hydrogel formulation decreased the blood glucose concentration apparently (40-50% of initial blood glucose concentration) for at least 4-5h after administration, and no apparent cytoxicity was found after application. These results showed that HTCC-PEG-GP formulation can be used as nasal drug delivery system to improve the absorption of hydrophilic macromolecular drugs.

Preparation of uniform-sized agarose beads by microporous membrane emulsification technique.

Uniform-sized agarose beads were prepared by membrane emulsification technique in this study. Agarose was dissolved in boiling water (containing 0.9% sodium chloride) and used as water phase. A mixture of liquid paraffin and petroleum ether containing 4 wt% of hexaglycerin penta ester (PO-500) emulsifier was used as oil phase. At 55 degrees C, the water phase permeated through uniform pores of microporous membrane into the oil phase by a pressure of nitrogen gas to form uniform W/O emulsion. Then the emulsion was cooled down to room temperature under gentle agitation to form gel beads. The effect of oil phase, emulsifier, especially temperature on the uniformity of the beads were investigated and interpreted from interfacial tension between water phase and oil phase. Under optimized condition, the coefficient variation (C.V.) showing the size distribution of the beads was under 15%. This was the first report to prepare uniform agarose beads by membrane emulsification, and to investigate the effect of temperature on the size distribution of the droplets and beads. The beads with different size can be prepared by using membranes with different pore size, and the result showed that there was a linear relationship between the average diameter of beads and pore size of the membranes; beads with diameter from 15 to 60 microm were able to obtain in this study.

Preparation and characterization of uniform-sized chitosan microspheres containing insulin by membrane emulsification and a two-step solidification process.

Chitosan microsphere has important application in controlled release of protein and peptide drug, because it shows excellent mucoadhesive and permeation enhancing effect across the biological surfaces. In the conventional preparation methods of chitosan microsphere, the W/O emulsion was usually prepared by mechanical stirring method, and then the droplets were solidified by glutaraldehyde. There existed limitation and shortage such as broad size distribution, de-activity of bio-drug and difficulty in drug release because protein and peptide drug have the same amino group as chitosan. In this study, we established a method to prepare uniform-sized microsphere, and solve above problems by combining a special membrane emulsification technique and a step-wise crosslinking method. That is, the chitosan/acetic acid aqueous solution was pressed through the uniform pores of a porous glass membrane into a paraffin/petroleum ether mixture containing PO-500 emulsifier, to form a W/O emulsion with uniform droplet size. Then, the uniform droplets were solidified by a two-step crosslinking method. At the first step, tripolyphosphate (TPP) solution was dropped gradually in the emulsion, TPP diffused into the droplet to crosslink chitosan by an ionic linkage, generating a microgel. At the second step, an adequate amount of glutaraldehyde was added. The solidification conditions of the two-step process were optimized by investigating the effects of solidification conditions on morphology of microspheres, encapsulation efficiency (EE), drug activity and release profile in vitro. The suitable preparative conditions were determined as follows: pH value of aqueous phase and TPP solution was 3.5-4.0, the molar ratio of amino group of chitosan to aldehyde group of glutaraldehyde was 1:1 and the crosslinking time of glutaraldehyde was 60 min.