Enhanced antitumor effect of curcumin loaded solid lipid nanoparticles in Dalton’s ascites lymphoma mice

Curcumin is widely known for its antibacterial, antioxidant and anti inflammatory effects and has been reported to possess anticancerous activity as well. However, its medical application is limited because of poor bioavailability and rapid metabolism. In this study, we encapsulated curcumin in solid lipid nanoparticles and studied its anticancerous effect in Dalton’s Ascites Lymphoma (DAL) mice model. The physicochemical characteristics of curcumin solid lipid nanoparticles (CUR-SLN) were assessed and the anticancer efficacy was determined by in vivo studies. The curcumin solid lipid nanoparticles were synthesized by solvent emulsification evaporation method with particle size less than 100 nm. Antitumor effect of nanocurcumin (50 mg/kg) and curcumin (100 mg/kg) was evaluated in Dalton’s Ascites Lymphoma bearing mice. Pathological and immunohistochemical parameters were studied. Mean survival time and percentage increase in lifespan were assessed. Nanocurcumin group showed more significant influence in reducing tumor volume and weight, inducing apoptosis, reducing angiogenesis and invasion restoring antioxidant parameters and increased mean survival time. Curcumin and nanocurcumin inhibited the activation of nuclear factor-kappa B (Nf-kB), and thereby proved the pathway by which it induced anti-angiogenic and anti-invasive property.

Series of experiments performed with the droplet evaporation method on low potencies

Homeopathic preparations in low potencies, containing still measurable quantities of the starting substance, constitute a unique research field in homeopathic basic research. Here a series of experiments is presented carried out by means of the droplet evaporation method (DEM), investigating the specificity of the method, and presumed effects of the succussion procedure applied in the production of homeopathic preparations. Methods:DEM analysis consisted in the evaporation of droplets of the potencies perse placed on microscope slides. Resulting patterns were photographed. Images were evaluated by means of ImageJ software, by measuring grey level distribution, texture, and fractality. The experimentation consisted of four series: (i) screening (1x­6x potencies from 19 substances), (ii) differentiation experiments (2x­6x potencies of Echinacea, Baptisia, Luffa, and Spongia), (iii) differentiation between succussed (100 or 10 times) and unsuccussed samples (Echinacea 2x, Baptisia 3x, Baptisia 4x, Luffa 4x, and Spongia 6x). (iv) investigation of the influence upon the patterns of single compounds present in a remedy complex. The experimental set-up stability was examined by systematic positive control experiments. Results:(i) Homeopathic preparations of mineral origin showed the greatest form variety, whereas those of vegetal origin created fractal patterns in the potency range 2x­4x. (ii) Differentiation of potencies of different origin at the same dilution level was possible from 2x to 4x. (iii) In all potency levels, succussed (100 and 10 times) and unsuccussed variants could be significantly differentiated. Significant differences between all variants were found in some cases in potency levels 4x and higher. In general, application of succussion reduced size, homogeneity, and complexity of the DEM patterns. (iv) Patterns of a remedy complex Luffa 4x -Mercurius bijodatum 9x showed a clear predominance of the Luffa 4x; however also the second component, present in a much lower concentration, influenced significantly the pattern of the remedy complex as also differed significantly from the pattern of succussed water control. Conclusions:The results suggest that DEM is a suitable tool for scientific investigation of homeopathic preparations in the low potency range. DEM might be applied to assess further research questions, such different potentization procedures (vessel shape, overhead volume, material), storing time, and difference between batches.

Formation of Self-organized Structures in Drying Droplets: a Promising Analytical Tool for Homeopathy Basic Research

The droplet evaporation method (DEM) is based on the evaporation-induced pattern formation in droplets and is applied mainly for medical diagnosis[1].Here, we present aseries of experiments performed by our team showing DEMs potential also forhomeopathy basic research, in particular, for the investigation of(i) low potencies, (ii) low potency complexes (physical model), and (iii) the action of high potencies (plant-based model).Methods:(i) DEM differentiated significantly between Luffa, Baptisia, Echinacea, and Spongiauntil 4x[2]. Furthermore, the patterns varied in function of the numberof succussion strokes (0, 10, or 100) applied during potentization[3]. The performance of chaotic succussions vs. laminar flow vs. slight mixing during the potentization of Viscum album quercus3x influenced the DEM patterns; the chaotic succussions reduced, whereas laminar flow enhanced the patterns complexity vs. the unsuccussed control.(ii) The addition of Mercurius bijodatus9x to Luffa4x changed significantly the DEM patterns, even if the material quantity present in the 9x potency lied far beyond that of ultrapure water.(iii) Leakages obtained by placing healthy or arsenic-damaged wheat-seeds into Arsenicum album45x orheat-damaged intoZincum metallicum30c vs. water created significantly different DEM structures [4, 5]. Results:The damaged seeds put into the potency created structures characterized by a higher complexity than those obtained from damaged seeds put into control water. Furthermore, the potency action seemed to increase with rising numbers ofsuccussion strokes applied during potentization,ascould be shown by means of DEM patterns and germination rate using the same wheat-seed model[6].In all our studies, the pattern evaluation was computerized (texture and fractal analysis performed by means of ImageJ) or based on deep-learning algorithms and the robustness of the experimental system was checked by means of systematic control experiments.Conclusion:DEM together with other similarmethods has also been reviewed by our team for what concerns theapplication in homeopathy basic research[7].

Formulation of stomach-specific floating microparticles of nizatidine and their radiographic evaluation

Nizatidine is an anti-secretogogue and a gastroprotective drug with a half-life of 1-2 h and is well absorbed in the stomach. This study aimed to optimize the process and develop floating microparticles of nizatidine that are based on low methoxyl pectin. Oil-in-oil dispersion method and Taguchi orthogonal array design were employed, and the prolonged residence time of the microparticles in the stomach was demonstrated. The constraints for independent variables, viz. A-polymer, B-internal solvent volume, C-surfactant, D-stirring rate and E-stirring time were set to generate the experimental runs. Particle size, percentage yield, micromeritic properties, entrapment efficiency, in vitro buoyancy and in vitro release were characterized. Surface morphology, zeta potential, in vitro release kinetics and in vivo floating performance of the optimized formulation was examined. The microparticles were free-flowing, irregular in shape and had a mean particle size distribution of 73-187 µ. Low methoxyl pectin played a predominant role in achieving buoyancy and optimum gastric retention for the modified release of the drug, suggesting Korsmeyer-Peppas model as the possible release mechanism. In vivo radiographic study in rabbits revealed that the drug was retained in the stomach for a period of 6 h. These results indicate that nizatidine floating microparticulate system provides modified drug release for the effective treatment of gastric ulcer

Vitamin C as a shelf-life extender in liposomes

Abstract The objective of this study was to evaluate the influence of vitamin C (VC) on the stability of stored liposomes under different climatic conditions. Liposomal formulations containing 1 mg/mL of VC (LIP-VC) and blank formulations (LIP-B) were prepared by the reverse-phase evaporation method. After preparation, they were characterized according to their refractive index, average vesicle diameter, polydispersity index (PDI), zeta potential, pH, content, encapsulation efficiency (EE%), morphology, stability and antioxidant activity. For stability, LIP-VC and LIP-B were stored in different climatic conditions (4 °C, 25 °C and 40 °C) for 30 days. The LIP-VC presented 1.3365 refractive index, 161 nm of mean diameter, 0.231 PDI, -7.3 mV zeta potential, 3.2 pH, 19.4% EE%, spherical morphology, 1 mg/mL of VC content, and antioxidant activity of 12 and 11.4 μmol of TE/mL for the radical DPPH and ABTS+, respectively. During stability, the LIP-B stored in 40 °C showed an instability in the parameters: PDI, vesicle size and zeta potential after 15 days, while the LIP-VC remained stable in its size and PDI for 30 days. After that, it is shown that VC can be used as an antioxidant and stabilizer in liposomes to increase the stability and shelf-life of vesicles.

Determination of gross α and gross β radioactivity in IAEA-2020-intercomparison samples / 中华放射医学与防护杂志

Objective:To summarize the practices in measuring the gross α and gross β radioactivity in IAEA-2020-intercomparison samples, which could be expected to be beneficial to the similar analysis and research.Methods:With 241Am, Th, 90Sr/ 90Y, 40K and 137Cs solution as standard materials, the gross α and gross β radioactivity in water and aerosol samples were determined using thin source method. With 241Am, 40K powder as standard materials, the gross α and gross β radioactivity in water and fish samples were measured using thick source method combined with evaporation. Results:The result showed that the relative deviation and Z-score by using thin source method were 4.12%-31.6% and 0.14-1.71, respectively, and those from thick source combined with evaporation were 2.63%-32.5% and 0.11-0.93, respectively, with the acceptance rate being 100%. Conclusions:Generally, standard material shall be selected in the same types of radionuclides and energies as in samples. The thin source method is appropriate for emergency monitoring in the event of an accident. The thick source combined with evaporation should be perfered to the environmental monitoring or the analysis of unknown samples in laboratory. And then an intercomparison should be done with thin source method based on the radioactivity in samples. This work can provide a technical reference for similar measurements.

Comparison of Microemulsion and Solvent Evaporation Technique for Solubility Enhancement of Amlodipine Besylate

@#Introduction: Amlodipine besylate is a calcium channel blocker indicated for hypertension and angina. It is described as slightly soluble in water and due to its limited solubility, it may result in poor bioavailability. The aim of this study is to enhance the solubility of amlodipine besylate using solvent evaporation method and microemulsion technique and to compare the two methods. Method: Solid dispersions (SD) of amlodipine besylate were developed by employing solvent evaporation method. PEG6000 was the polymer of choice and different drug:polymer ratios were used. Evaluation of the prepared SDs include solubility studies, dissolution studies and scanning electron microscopy (SEM). As for the microemulsion technique, microemulsions were prepared by phase titration method and the optimized microemulsion formulation was then characterized for solubility studies and dissolution studies. Results: SD3 with drug:polymer ratio of 1:4 achieved the highest solubility which was 96.97 mg/ml ± 0.92 whereas the solubility of the optimized microemulsion was found to be 112.54 mg/ml ± 0.92. In solvent evaporation method, as the drug:polymer ratio increases, the solubility and dissolution rate of SDs increases. Conclusion: The two methods had significantly enhance the solubility of amlodipine besylate however the microemulsion technique showed better solubility profile.

Application of design technology for preparing Lingzhu Powder particles based on solvent evaporation method / 中国中药杂志

Targeting the deficiencies of Lingzhu Powder, this study introduced the particle design technology to improve its quality. Based on the mechanism of particle design for powder and the characteristics of solvent evaporation method, composite particles consisting of Succinum, Cinnabaris, and artificial Bovis Calculus were prepared. And the powder properties of composite particles and physical mixtures as well as the content uniformity of toxic components were investigated for exploring the technological advantages of particle design in improving the quality of Lingzhu Powder. The results showed that the composite particles prepared using solvent evaporation method and particle design technology were micro-particles, and the stable agglomerate structure could be observed under SEM. Composite particles exhibited better fluidity and compliance in oral intake than physical mixtures. The differences in chromatism, bulk density, and content uniformity of the composite particles were smaller than those of physical mixtures, and the corresponding RSD values \[4.8%, 1.8%, 3.4%(bilirubin), and 0.63%(HgS), respectively\] were smaller. The solvent evaporation combined with particle design technology can be utilized to significantly improve the quality of Lingzhu Powder, which has provided new ideas for the optimization of the quality of traditional Chinese medicinal powder.

Effect of Lockdown amid COVID-19 Pandemic on Weather Parameters of Mid Hill Region of Jammu District of J&K, UT

Aim: A study was conducted in mid hill region of Jammu district, J&K to analyze the impact lockdown amid covid-19 pandemic on weather parameters so as to define it as a tool to mitigate the pace of climate change. Methodology: Day and night temperature readings were recorded fortnightly during 22nd March to 10th June 2020 from maximum and minimum thermometer, relative humidity from dry and wet bulb thermometers in stevenson screen, rainfall values from ordinary rain gauge, evaporation readings from pan evaporimeter and soil temperature at different depth from soil thermometers. Results: After analyzing the data statistically using “Descriptive statistics” in MS-Excel 2010, it was observed that after the implementation of lockdown and with the beginning of unlock down the change in day temperature was -8.07% from normal mean value, night temperature was -4.44% from normal mean value, rainfall pattern was 30.00% more from normal mean value, Relative Humidity (morning) pattern was 6.94% more from normal mean value, relative humidity (evening) pattern was 20.94% more from normal mean value, evaporation pattern was 7.66% more from normal mean value. The average change in soil temperature in morning at 5 cm, 10 cm and 20 cm depth was -3.46%, -3.84% and -7.23% as compared to year 2019 (22nd March to 10th June 2019) mean value and the change in soil temperature in evening at same depths was -7.69%, -6.31% and -4.14% from year 2019 (22nd March to 10th June 2019). Conclusion: With the variable significant pattern observed in almost all parameters, it can be concluded that lockdown might be an effective tool in mitigating pace of climate change in future.

Formulation and optimization of Enalapril Maleate-loaded floating microsphere using Box–Behnken design: in vitro study

The objective was to prepare an Enalapril Maleate (EnM)-loaded floating microsphere with minimum particle size,maximum drug loading, and drug entrapment efficiency. Formulations were prepared by varying drug-to-polymerratio (A), solvent ratio (B), and stirring time (C). The solvent evaporation method was used to prepare the microsphere.“Box–Behnken’s design” (3 factors × 3 levels) was utilized for optimization. The independent variables were polymerto-drug ratio (A), solvent ratio (B), and stirring time (C), while particle size (R1), drug loading (R2), and entrapmentefficiency (R3) were considered as dependent variables. EnM-loaded alcohol microsphere (Formulation-A) wasprepared and optimized. Both Formulation-A and EnM-loaded acetonitrile microspheres (Formulation-B) weresubjected to morphological, micrometric, characterization, and in vitro release studies. The particle size, drug loading,and entrapment efficiency of Formulation-A and Formulation-B were 143 ± 27.75 µm, 37.31% ± 5.73%, and 76.89%± 4.97%, and 158.13 ± 25.1 µm, 40.13% ± 6.12%, and 99.19% ± 1.14%, respectively. The cumulative drug releasesof Formulation-A and Formulation-B were 90.52% ± 4.11% and 86.23% ± 3.81%, respectively. Both formulationsfollowed the Higuchi model of drug release. EnM-floating microsphere was effectively prepared and both formulationsshowed excellent continuous release properties for more than 12 hours.

Formulation And Evaluation Of Chlorothalidone Loaded Mouth Dissolving Film-A Bioavailability Enhancement Approach Using Multilevel Categoric Design

Objective: The intension of the present study includes fabrication and optimization of mouth dissolving film loaded with Chlorothalidone by solvent evaporation techniques using two components and their three levels as multilevel Categoric design. Methods: Major problem associated with the development of film loaded with BCS class II drug is to increase its solubility. Here the Chlorothalidone solubility achieved by co-solvents, such as methanol. After dissolving the drug in co-solvent, this drug solution is poured into an aqueous dispersion of Hydroxypropyl Methylcellulose E5 (HPMC E5) and Polyethylene glycol 400 (PEG 400). The two independent variables selected are factor A (concentration of HPMC E5) and factor B (concentration of PEG 400) was selected on the basis of preliminary trials. The percentage drug release (R1), Disintegration time in sec (R2) and folding endurance (R3) were selected as dependent variables. Here HPMC E5 used as a film former, PEG 400 as plasticizer, mannitol as bulking agent, Sodium starch glycolate as a disintegrating agent, tween 80 as the surfactant, tartaric acid as saliva stimulating agent, sodium saccharin as a sweetener and orange flavour etc. These fabricated films were evaluated for physicochemical properties, disintegration time and In vitro drug release study. Results: The formulation F6 has more favorable responses as per multilevel categoric design is % drug release about 98.95 %, average disintegration time about 24.33 second and folding endurance is 117. Thus formulation F6 was preferred as an optimized formulation. Conclusion: The present formulation delivers medicament accurately with good therapeutic efficiency by oral administration, this mouth dissolving films having a rapid onset of action than conventional tablet formulations.

Clinical observation of physiotherapy in the treatment of evaporative dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To explore the clinical efficacy of physical therapy in the treatment of hyperevaporative dry eyes.<p>METHODS: From October 2018 to April 2019, 70 patients(140 eyes)with evaporative dry eye were diagnosed in the ophthalmology clinic of the Affiliated Hospital of Gansu University of Traditional Chinese Medicine. Randomly divide the patients into 35 cases(70 eyes)in the control group for basic treatment(sodium hyaluronate eye drops), and 35 cases(70 eyes)in the treatment group underwent acupuncture combined with traditional Chinese medicine iontophoresis treatment based on the control group. 1 time/d, treatment 3wk(treatment 6d, rest 1d). Before and after treatment, the tear height(TMH), tear film rupture time(BUT), Schirmer Ⅰ test(SⅠt), and corneal fluorescein staining(FL)were observed.<p>RESULTS: The pre-treatment data of the TMH treatment group and the control group were 0.21(0.15, 0.27)and 0.21(0.15, 0.28)mm respectively; the postoperative data of the treatment group and the control group were 0.24(0.21, 0.29), 0.23(0.19, 0.29)mm. The comparison between groups was <i>P</i><0.05. The preoperative data of the SⅠt treatment group and the control group were 5.00(3.00, 7.00)and 6.00(4.00, 7.00)mm/5min respectively; the postoperative data of the treatment group and the control group were 10.00(8.00, 12.00), 7.00(6.00, 8.00)mm/5min. The preoperative data of the BUT treatment group and the control group were 2.75(1.38, 6.15)and 3.25(1.38, 5.03)s respectively; the postoperative data of the treatment group and the control group were 8.90(6.90, 12.85), 7.15(5.40, 9.53)s. The preoperative data of the SⅠt treatment group and the control group were 4.50(3.00, 6.00)and 5.00(3.00, 6.00)min respectively; the postoperative data of the treatment group and the control group were 1.00(0.75, 2.00), 3.00(2.00, 4.00)min, the comparison between groups was <i>P</i>>0.05. Comparison of the data difference between the treatment group and the control group before and after showed that the treatment group had a more significant effect than the control group(<i>P</i><0.05).<p>CONCLUSION: Physical therapy has a significant clinical effect in treating dry eyes with excessive evaporation, and it is worthy of clinical recommendation.

Carboxymethyl Bletilla striata polysaccharide-chitosan@curcumin polyelectrolyte complex films: Preparation and characterization / 中草药

Objective: To prepare carboxymethyl Bletilla striata polysaccharide-chitosan@curcumin (CM-BSP) polyelectrolyte complex films, optimize their preparation technology, and evaluate its quality. Methods: CM-BSP was synthesized, then CM-BSP and CS formed water-insoluble complex by electrostatic bonding, the Cur-loaded polyelectrolyte complex films were prepared by a volatilization of solvent method. The formulation and preparation technology were optimized using an orthogonal design method and the morphology and structure were observed by scanning electron microscopy and fourier transform microscopic infrared spectroscopy. Results: The optimal prescription was of CM-BSP 117 mg, CS 233 mg, glycerol 25%, Cur 20 mg. The mean thickness of Cur-loaded polyelectrolyte complex films was (74.0 ± 2.0) μm, drug loading capacities was 95.41%, and in vitro release rate was 93.78%. Conclusion: The obtained polyelectrolyte complex films displayed an smooth exterior inspection, uniform distribution, good drug loading capacities and in vitro release rate.

Different preparations of magnolol: Preparation, characterization and pharmacokinetics comparative study in SD rats / 中草药

Objective: To prepare magnolol solid dispersions (Mag-SD), magnolol phospholipids complex (Mag-PC) and magnolol solid lipid nanoparticles (Mag-SLN), and compare their effects on the pharmacokinetics in vivo. Methods: Solvent evaporation method was used to prepare Mag-SD and Mag-PC. Their existential state of Mag in Mag-SD and Mag-PC were analyzed by X-ray power diffraction (XRPD). High pressure homogenization method was employed to prepare Mag-SLN, its particle size and Zeta potential were also studied. The dissolution in vitro of Mag-SD, Mag-PC and Mag-SLN were also studied compared to magnolol suspension. SD rats in each group were administered intragastrically with magnolol, Mag-SD, Mag-PC and Mag-SLN, respectively. The concentration of magnolol in blood was analyzed by HPLC, and the main pharmacokinetic parameters were obtained. The pharmacokinetic behavior and bioavailability of magnolol, Mag-SD, Mag-PC and Mag-SLN were also compared. Results: The results of XRPD indicated that magnolol showed an amorphous state in Mag-SD and Mag-PC. The average particle size and Zeta potential of Mag-SLN was (161.37 ± 3.77) nm and (-29.16 ± 1.83) mV, respectively. The results of dissolution in vitro indicated that the cumulative dissolution of magnolol was 30.6% within 12 h. Mag-SD, Mag-PC and Mag-SLN enhanced its cumulative dissolution to 96.3%, 76.4% and 45.9%, respectively. The results of pharmacokinetics in vivo showed that Cmax, AUC0-t and AUC0-∞ of Mag-SD, Mag-PC and Mag-SLN were enhanced greatly compared to magnolol suspension. Mag-PC, Mag-SD and Mag-SLN increased its Cmax from (429.67 ± 53.12) ng/mL to (533.62 ± 59.01), (721.73 ± 103.44) and (1 063.21 ± 108.22) ng/mL, respectively. The bioavailability of Mag-SD, Mag-PC and Mag-SLN were enhanced to 1.38, 2.12 and 3.45 times, respectively. Conclusion: Mag-SD, Mag-PC and Mag-SLN could promote the absorption of magnolol in SD rats notably. In addition, Mag-SLN could give a better effect on the bioavailability.

Preparation, characterization and physicochemical properties of arbutin phospholipid complex / 中草药

Objectives To prepare arbutin phospholipid complex (APC) to improve the skin permeability of arbutin and discuss the formation mechanism of APC. Methods Solvent evaporation method was used to prepare APC. The formation of APC was confirmed by differential scanning calorimetry (DSC), X-ray diffraction (XRD), infrared spectroscopy (IR), 1H nuclear magnetic resonance (1H-NMR), scanning electron microscopy (SEM) and transmission electron microscope (TEM). The solubility, skin permeability and the ability to inhibit tyrosinase of APC were evaluated. Results The analysis showed that the weak interaction between phospholipid and arbutin molecules formed APC. The solubility of arbutin in APC in n-octanol increased from 1.29 µg/mL to 9.54 µg/mL, and the formation of APC effectively increased the lipophilicity of arbutinn. In vitro release study demonstrated that APC exhibited sustained release behavior. Ex vitro penetration studies showed that arbutin was difficult to reach the subcutaneous tissue through the skin, but APC showed strong penetration ability, of which permeation flux was improved from 0.02 mg/cm2 to 0.42 mg/cm2. Enzyme inhibitory activity test showed that the inhibition of APC on tyrosinase activity was 1.85 times of arbutin. Conclusions The formation of the complex improved the bioavailability of arbutin, and the complex held higher application potential for medicinal and cosmetic.

Assessment of Heat and Mass Transfers by the Evaporation of a Large Impoundment under Dry and Hot Climate: Case of Burkina Faso

This paper aims to report a numerical study of the assessment of heat and mass transfers by evaporation of a large impoundment under Burkina Faso climate conditions. This impoundment is considered as a parallelepiped which upper face, in contact with the ambient environment and subject to solar radiation, is the seat of a natural convection-based evaporation. The intensity of this evaporation is modeled by a correlation in the literature. Transfers into water are made by natural convection. They are caused by temperature differences due to solar radiation and ambient conditions (wind, hygrometry of the air,) on water. These transfers are described by the Navier-Stokes equations and energy and the initial and boundary conditions associated with them. The finite volume method and the SIMPLE algorithm were used for speed-pressure coupling. The systems of algebraic equations deduced from the discretization of transfer equations and boundary conditions associated with them are solved with Thomas’ algorithm, the SIMPLE algorithm and an iterative procedure because evaporated water quantity depends on the temperature and concentration of water vapor at the surface of the impoundment which are the unknowns of the problem. The numerical model developed is validated in relation to previous work and experimental data from Burkina Faso meteorology. The results obtained concern the evolution of the evaporated water flux under dense solar flows, a relative humidity of the air proportional to the wind speed and also the evolution of the evaporated water flux against the solar flux density for high relative moisture content. Also the evolution of the evaporated water flow against the depth of the impoundment for a solar flux density, relative humidity and the temperature of the surface of the body of water is given. The determination of evaporated water flux for typical years was calculated on a 10-year period. The results obtained show that the flux of evaporated water increases with a high solar flux rate and decreases for a high relative humidity level.

Formulation And Development Of Gastroretentive Drug Delivery System Of Efavirenz

Efavirenz, a non-nucleotide reverse transcriptase inhibitor is an important drug for treating patients with Human Immunodeficiency Virus infections. It belongs to BCS class II have low solubility and poor intrinsic dissolution rate. It is highly basic (pKa 10.2) which makes it suitable candidate for floating dosage form for continuous delivery in stomach.The study was aimed to improve the solubility by solid dispersion technique.Saturation solubility study and drug content were evaluated for solid dispersion preparation. Saturation solubility shows 8 fold increases in 0.1 N HCL compared to plain drug and drug content was found to be between 95%-102%. Further effervescent floating gastroretentive drug delivery system was prepared by 32 full factorial design with independent variables i.e., concentration of HPMC K100 as matrix forming agent and citric acid as gas generating agent. Lag time, floating time, percent drug release were studied as responses. The optimized batch exhibited floating lag time of 40 sec and the in vitro release studies showed 89.5% drug release in 9 h and tablet remained floating for greater than 8 h. The study thus demonstrated that solubility is increased by solid dispersion technique and floating delivery systems may increase solubility and bioavailability of Efavirenz.

Clinical observation of drug combined with physiotherapy in the treatment of dry eye caused by MGD / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To compare the clinical curative effects of meibomian gland dysfunction(MGD)caused by evaporative dry eye by utilizing levofloxacin eye gel and Tobramycin and Dexamethasone Ophthalmic Ointment, respectively.<p>METHODS: The 180 cases(360 eyes)with dry eye(evaporative type)caused by confirmed meibomian gland dysfunction were randomly divided into two groups(<i>i.e.</i> A and B): In group A, 90 individuals with 180 eyes were treated with levofloxacin eye gel+ sodium hyaluronate eye solution; The other 90 cases in group B took Tobramycin and Dexamethasone Ophthalmic Ointment+ sodium hyaluronate eye drops for curing the MGD. In addition, the same comprehensive therapy were used to the MGD patients in groups A and B, after surface anesthesia on binoculus, secretion, obstructing meibomian gland secretions, were discharged by utilizing cotton stick to extrusion mass weekly and four times consecutive treatments were regard as a course of treatment. To remove residual the thin oil soften lipid in meibomian gland, heat can be applied to the eyelids with hot water(around 45℃)on towel for 15min and do that three times a day. After each hot compress, we use levofloxacin eye gel to the patients in group A by dropping into the conjunctival sac and apply to the root of the eyelid lashes. The group B of 90 patients were applied Tobramycin and Dexamethasone Ophthalmic Ointment to the root of the eyelid lashes. All patients were dripped odium eye drops eye into their eyes four times a day. <p>RESULTS: After treatment(<i>Z</i>= -0.64, <i>P</i>=0.524), there were no significant differences in clinical symptoms(<i>Z</i>= -1.37, <i>P</i>=0.171), secretion characteristics(<i>Z</i>= -1.06, <i>P</i>=0.288), tear film rupture time and tear secretion time between groups A and B(<i>P</i>>0.05). Corneal fluorescence staining score: group A(cured 83.3%, improved 11.1%, ineffective 5.6%)and group B(cured 55.6%, improved 27.8%, ineffective 16.7%). The therapeutic effect of group A was better than that of group B, with statistical significance(<i>Z</i>= -4.02, <i>P</i><0.001).<p>CONCLUSION: Physical therapy for meibomian gland dysfunction caused by evaporative dry eye is given priority, and medication is treated as adjunctive therapy. Generally, the patients can achieve totally anti-inflammatory, antibacterial, safe and stable, without side effects by using levofloxacin eye gel. However, the patients with worst condition and lingering illness should cured by Tobramycin and Dexamethasone Ophthalmic Ointment. In addition, statistical significant difference is not found between the two drugs on curative effects.

Preliminary establishment of dry eye model in non-obese diabetic mice / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To determine the pathological changes in ocular surfaces dry eye excessive evaporation non-obese diabetic(NOD)mice model and to preliminarily explore the feasibility of diabetic dry eye model.<p>METHODS: In this study, 40 females NOD mice were selected. The experimental group consisted of NOD mice that were diagnosed with diabetes while the normal control group consisted of those NOD mice without spontaneous diabetes. Hypodermic injection of Scopolamine hydrobromide(0.5mg/0.2mL)was administered under 40% humidity to the experimental group and placed in a controlled drying box for 12h a day. This was to achieve a dry eye model. Testing indicators on the 1, 7, 10 and 14d after modeling, phenol red thread test was used to measure tear secretion and the eye sections were stained with periodic acid-Schiff(PAS)to examine the morphology and number of conjunctival goblet cells. On the 10d after modeling, the changes in the corneal epithelium were visualized after staining with hematoxylin. <p>RESULTS:For the NOD mice of the experimental group, the tear secretion was gradually decreased with timing, while there were no obvious changes in the normal control group. The volume of the conjunctival goblet cells of the experimental group became larger, and on the 1d after the molding, the experimental group had decreased density of the goblet cells when compared with the normal control group(<i>P</i>=0.008). From the 7d after the molding, as the time was prolonged, the density of the goblet cells was gradually decreased and the differences between the two group at same time point were significant(all <i>P</i><0.001). Besides, it was required to observe the corneal epithelium of the two groups on the 10d. The result shows that the corneal epithelium became thinned, some epithelial cells were denatured, and stromal cells became edema.<p>CONCLUSION: Dry eye model of NOD mice was preliminary established, and the changes of ocular surface were similar to those of dry eye in the clinic.

Preparation and characterization of ginkgolide K-loaded PLGA-PEG nanoparticles and its neuroprotective activity in vitro / 中草药

Objective To prepare and characterize ginkgolide K-loaded mPEG-PLGA [poly (D,L-lactide-co-gly-colide)-block-poly (ethylene glycol)] polymer nanoparticles (GK-mPEG-PLGA-NPs) and to evaluate its neuroprotective effect on the H2O2-induced PC12 cells injury in vitro. Methods The PLGA-PEG-COOH polymer was selected as carrier and double emulsion solvent evaporation technique was employed to prepare the stealth nanoparticles. The encapsulation efficiency (EE) and drug load (DL) of GK-mPEG-PLGA-NPs were investigated by HPLC. The size distribution, zeta potential, and surface morphology of GK-mPEG-PLGA-NPs were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The in vitro release of GK-mPEG-PLGA-NPs was examined using phosphate buffer solution (pH 7.4) as the releasing medium for 24 h. The H2O2-induced PC12 cells injury models was established for the investigation of the protective effect of GK-mPEG-PLGA-NPs on nerve cells in vitro. Results EE and DL of GK-mPEG-PLGA-NPs was (83.40 ± 2.85)% and (3.26 ± 0.24) mg/g, respectively. The average diameter of GK-mPEG-PLGA-NPs was (93.19 ± 2.77) nm and zeta potential was (-11.93 ± 1.71) mV. The cumulative rate of drug release was (90.5 ± 4.0)% after 60 h in phosphate buffer solution. GK-mPEG-PLGA-NPs significantly inhibited the apoptosis of PC12 cells and the release of lactic dehydrogenase induced by H2O2. However, the protective action of GK-mPEG-PLGA-NPs on the H2O2-iduced PC12 cells injury was significantly weaker than that of GK. Conclusion Our results proved that GK-mPEG-PLGA-NPs had a sustained release behavior in vitro and the neuroprotective effect of GK-mPEG-PLGA-NPs on H2O2-induced PC12 cells, which indicates that GK-mPEG-PLGA-NPs has the prospect of application and deserves further research. Key words: ginkgolide K; mPEG-PLGA; in vitro release; in vitro neuroprotection; d