In vitro evaluation of saxagliptin and metformin hydrochloride sustained-release tablets / 中国药科大学学报

@#In order to evaluate the consistency of the release behavior between the self-made saxagliptin and metformin hydrochloride sustained-release tablets and the reference preparations in vitro, the similarity of the dissolution curves between the self-made preparations and the reference preparations in four dissolution mediums: HCl (pH 1.0), acetate buffer saline (pH 4.5), phosphate buffer saline (pH 6.8) and pure water, and the gel morphology and strength of the self-made preparations and the reference preparations in the HCl (pH 1.0) solution medium were compared.Results showed that in four dissolution mediums, the dissolution rates of saxagliptin in the self-made preparations and the reference preparations at 15 min were greater than 85%, and the ?2 similarity factors of metformin hydrochloride were 89, 83, 80, 86, all greater than 50, so the dissolution of the self-made preparations was consistent with those of the reference preparations.The volume expansion rate, water absorption rate and erosion rate were consistent with those of the reference preparations, and the gel strength of the self-made preparations was the same as that of the reference preparations.The in vitro release behaviors of the self-made preparations and the reference preparations are consistent, which provide a good guarantee for bioequivalence.

Preparation and in vitro evaluation of forsythoside A-loaded exosomes / 中国中药杂志

A drug delivery system of forsythoside A-loaded exosomes(FTA-Exos) with high biocompatibility and low immunogenicity was established to investigate its impact on the migration of human lung epithelial adenocarcinoma A549 cells. The exosomes from A549 cells were extracted and purified by ultra-high speed centrifugation and ultrafiltration. FTA-Exos were prepared by ultrasonic incubation, and characterized by particle size analysis, transmission electron microscopy, and Western blot assay. The uptake of FTA-Exos by A549 cells was observed under the laser confocal microscope, and the impact of FTA-Exos on the migration of A549 cells was investigated by cell scratch assay. The results showed that the average particle size of the prepared FTA-Exos was(138.90±2.37) nm, which increased slightly after drug loading. The PDI was 0.291±0.013, and the average potential was(-10.1±0.66) mV. The FTA-Exos were spheroidal in appearance as observed by transmission electron microscope, with an obvious saucer-like double-layer membrane. Western blot assay indicated that the specific proteins CD63 and Alix were both expressed in exosomes. The laser confocal microscopy suggested that FTA-Exos were taken up by A549 cells and stably maintained in the cell for 4-8 h, and the fluorescence was significantly enhanced at 4 h. The scratch assay showed that the inhibitory effect of FTA-Exos on the migration of A549 cells was significantly stronger than that of forsythoside A(P < 0.05). In conclusion, the drug delivery system of FTA-Exos established in this study had good stability, reliable preparation process, and potent inhibitory effect on the migration of A549 cells in vitro, which can provide an important reference for subsequent in-depth research and application.

Preparation and in vitro evaluation of self-assembling peptide hydrogel loaded with doxorubicin / 中国组织工程研究

BACKGROUND: Chemotherapy is an important method for treating osteosarcoma, but traditional small molecule therapy is not ideal for clinical efficacy and has serious adverse reactions. Therefore, it is necessary to develop a new method for osteosarcoma, which can anti-tumor at low doses and reduce adverse reactions. OBJECTIVE: To construct a self-assembling peptide hydrogel (SAPH) loaded with doxorubicin (DOX) and analyze its drug release performance and biocompatibility in vitro. METHODS: DOX was introduced into SAPH composed of FEFEFKFK (F, phenylalanine; E, glutamic acid; K, lysine), prepared to contain 20, 30, and 40 g/L DOX-SAPH of FEFEFKFK; the DOX mass concentration in this system was 2 g/L. Three kinds of DOX-SAPH were placed in PBS, and the amount of DOX released was regularly detected. Three DOX-SAPH extracts were co-cultured with rabbit bone marrow mesenchymal stem cells, and the cell survival rate was detected by CCK-8 method. The DOX solution containing different concentrations of DOX and the DOX-SAPH extract (containing FEFEFKFK 30 g/L) were co-cultured with MG63 human osteosarcoma cells, and the cell survival rate was detected by CCK-8 method. RESULTS AND CONCLUSION: (1) With the increase of the concentration of FEFEFKFK in the hydrogel, the sustained release effect of DOX-SAPH was enhanced. The cumulative drug release rate of DOX-SAPH at 20, 30, and 40 g/L at the 168th hour in vitro was 88%, 83%, and 80%. (2) The cells in 20 g/L DOX-SAPH extract group proliferated faster than 30 and 40 g/L DOX-SAPH extract group at 1, 3, and 5 days in vitro (P 0.05). When the concentration of DOX was higher than 12.5 mg/L, the cell toxicity of the DOX solution was greater than that of DOX-SAPH extract (P < 0.05). (4) The results show that DOX-SAPH has a good drug slow-release effect, which can inhibit the growth of MG63 osteosarcoma cells.

Preparation and in vitro evaluation of pH-sensitive drug releasing As2O3-loaded liposome / 中草药

Objective: To prepare pH-sensitive drug releasing As2O3 loaded liposome (CaAs-LP) and evaluate it in vitro. Methods: CaAs-LP was prepared by thin film dispersion and ion precipitation method. The particle size, PDI, and Zeta potential of CaAs-LP were measured by Malvern particle size analyzer; The morphology of the liposome was investigated by transmission electron microscopy; The drug loading and entrapment efficiency of CaAs-LP by inductively coupled plasma emission spectrum. In vitro release characteristics of CaAs-LP under different pH conditions were investigated by dialysis bag method. MTT assay was used to investigate the toxicity of carrier and CaAs-LP to MCF-7, U87 and HepG2 cells. Results: The prepared CaAs-LP were spherical and well-dispersed with particle size of (117.16 ± 1.94) nm. The encapsulation efficiency and the drug loading rate of CaAs-LP were (74.31 ± 2.11)% and (8.31 ± 0.13)%, respectively. In vitro release studies showed that CaAs-LP had the characteristics of sustained release and pH sensitive drug release, which can achieve specific drug release in the tumor environment. The carrier displayed remarkable biocompatibility in MCF-7, U87, HepG2 and L02 cells. MTT assay showed that the median lethal concentrations (IC50 values) of MCF-7, U87 and HepG2 cells were 11.91, 4.90 and 19.41 μmol/L, while L02 was 27.59 μmol/L, respectively, which showed strong inhibiting effect on tumor cells. Conclusion: CaAs-LP reveals significantly sustained and pH sensitive release characteristics. CaAs-LP is a potential drug delivery system against solid tumor with tumor micro-environment responsive.

Optimization of pH response and mitochondrial targeting bifunctional hyperoside liposomes by central composite design response surface methodology and its in vitro evaluation / 中草药

Objective: To optimize preparation of mitochondrial targeting hyperoside liposomes (DLD/Hyp-Lip), and study its stability in fetal bovine serum, in vitro release behavior and mitochondrial targeting. Methods: DLD/Hyp-lip was prepared by film dispersion method. Single factor experiment was carried out with entrapment efficiency and drug loading as indexes to investigate the effects of the ratio of phospholipids to hyperoside (Hyp) and DSPE-PEG (distearoyl phosphoethanolamine-polyethylene glycol) to DLD on DLD/Hyp-Lip. The formulation of DLD/Hyp-Lip was further optimized by central composite design response surface methodology. The appearance, size and potential of liposomes were observed by transmission electron microscope and particle size analyzer. The stability and drug release rate of liposomes in fetal bovine serum were evaluated by serum stability test and in vitro drug release test. The drug delivery system was evaluated by mitochondrial targeting. Results: The optimal formula of DLD/ Hyp-Lip was as follows: the ratio of total phospholipids to hyperoside was 12.50:1, the ratio of total phospholipids to cholesterol was 6.00:1, and the dosage ratio of DSPE-PEG to DLD was 3:5, the encapsulation efficiency was (95.57 ± 0.56) %, the drug loading was (8.55 ± 0.57) %. The prepared liposomes had good appearance, the particle size of the lip was (124.9 ± 3.4) nm, and the potential was (-6.2 ± 1.9) mV. It was stable in fetal bovine serum and accumulated in vitro release medium for 24 h. Mitochondrial targeting experiments showed that DLD/Hyp-Lip could promote the accumulation of drugs in the mitochondria. Conclusion: This method is simple and convenient, and can accurately and effectively optimize the preparation process of DLD/Hyp-Lip. The prepared DLD/Hyp-Lip has high encapsulation efficiency, small particle size, uniform distribution and good sustained-release effect, which lays the foundation for further in vivo research of DLD/Hyp-Lip. DLD/Hyp-Lip with hyperoside has good mitochondrial targeting of liver cancer cells and is a potentially efficient mitochondrial targeted drug delivery system for liver cancer cells.

Preparation and in vitro evaluation of vitamin K1-loaded erythrocyte drug delivery system / 国际药学研究杂志

Objective: To establish a vitamin K1(VK1)-delivery system with red blood cells as carrier. Methods: The VK1 self-emulsifying nano-emulsion, micelle and plasma solution were prepared to investigate the VK1 loading on red blood cells. The VK1- chitosan(CS)nanoparticles were prepared with different particle size by the 3 different preparation methods, and the effect of the particle size and charge property on the VK1-loading on red blood cells was investigated with the prepared VK1-CS nanoparticles. The encapsulation efficiency and drug loading were used as main indicators to investigate the appropriate drug loading method. Results: Due to the solubility of VK1 or the charge properties of nanoparticles, the drug loading and encapsulation efficiency of the red blood cell-encapsulated VK1 were quite low, and a large amount of drugs could not be loaded on the red blood cells. The ability of red blood cells to load VK1 was likely related to its Zeta potential. The VK1-CS nanoparticles prepared by the ion condensation method showed a good drug loading performance. Each milliliter of red blood cells could load 174.46 μg VK1 in the nanoparticles, and the loading rate was 85.11%. Conclusion: The VK1 loading by the red blood cells could be achieved by the electrostatic interaction between the positively charged chitosan nanoparticles and the negatively charged erythrocyte membrane.

In vitro comparison test for chemical solid oral generic drugs administered by nasogastric tubes / 国际药学研究杂志

At present, the dosage and administration items in the marketing instructions of some oral solid brand drugs approved in China include related contents for administration via nasogastric tube. In order to achieve consistency with the original drugs in quality and efficacy, the generic drugs investigators should confirm whether the generic drugs and the original drugs have the same in vitro characteristics under the conditions of administration by nasogastric tube. The purpose is to eliminate the clinical risks brought by the way of administration. This article summarizes the experimental design and evaluation points for the in vitro comparative study of the solid oral generic drugs which can be administered by nasogastric tube, while referring to the individual drug guidelines issued by FDA and the related literature published, so as to provide a reference for the technical system construction for the consistency evaluation of oral solid dosage forms.

In vitro Evaluation of Corn Germ Meal as Ruminant Feed

The present study was taken up to assess the chemical composition and in vitro nutritional worth of corn germ meal (CGM) in comparison to conventional oilseed cakes used in livestock feeding. The CP content of protein sources varied from 18.59% in CGM to 49.41% in soybean meal (SBM). CGM had the highest ether extract (EE) content, neutral detergent fibre (NDF), acid detergent fibre (ADF) and total carbohydrates. However, total ash, acid detergent insoluble crude protein (ADICP) and neutral detergent insoluble crude protein (NDICP) was lowest in CGM. In vitro net gas production in CGM (267.91 ml/g DM/24 h) was higher (P<0.05) than other conventional oil cakes. The digestibility of organic matter varied from 85.12% in DMC (deoiled mustard cake) to 96.19% in SBM. The ME availability was highest (P<0.05) in CGM (9.63 MJ/kg DM). Ammonical nitrogen in CGM was lower (P<0.05) than SBM and GNC (groundnut cake).The total volatile fatty acids (TVFA) production (mM/dl) was highest (P<0.05) in GNC (12.56) and lowest (P<0.05) in CGM (9.31). Methane production was lowest (P<0.05) in CGM than other conventional oil cakes. Hydrogen recovery (%) was higher (P<0.05) in CGM (65.76) and SBM (65.78) than other protein sources tested. Fermentation efficiency (%) was higher (P<0.05) in SBM (77.02) and GNC (76.75) while volatile fatty acids utilization index (VFA UI) was higher (P<0.05) in CGM (2.92) and DMC (2.84) than other protein sources tested. The results revealed that CGM can be used as a potential protein source for ruminants.

Development And In Vitro Evaluation Of A New Topical O/W Emulgel From Fruit Extract Of Pyrus Communis

Objective: The aim of the present study was to develop a new topical dosage form containing Pyrus communis fruit extract. Developed formulation was O/W Emulgel which was evaluated by its in vitro tests and its stability studies at different storage conditions. Methods: Hydroalcoholic Pyrus communis extract was prepared by the maceration process. A 4% Pyrus communis emulgel was prepared by the combination of emulsion and gel at a specific temperature and mixing through homogenizers. The formulations having different concentration of carbopol 940 (gelling agent) were placed at 8 °C, 25 °C, 40 °C and 40 °C+75%RH for 3 mo in order to find out the most stable formulation. After the selection of final emulgel formulation was eventually further evaluated for in vitro studies such as phase separation, centrifugation, rheology, pH, conductivity, organoleptic properties and mean droplet size over a period of 12 w at 8 °C, 25 °C, 40 °C and 40 °C+75%RH. Results: In vitro evaluation of the selected Pyrus communis emulgel formulation showed good resistance to phase separation on centrifugation, conductivity gradually increases due to oil in water emulgel and pH of formulation was gradually decreased. The rheological behavior was non-Newtonian pseudoplastic and showed shear thinning fluid behavior. Mean droplet size of Pyrus communis emulgel was 16.0±0.20 µm and after 90 d droplet size was 16.7±0.55 µm at high storage temperatures at 40 °C and 40 °C+75RH and no significant changes were observed at normal storage conditions at 8 °C and 25 °C. Conclusion: Pyrus communis emulgel fresh fruit extract showed stable formulation at different storage conditions. This new formulation will be a good addition to pharmaceutical dosage forms made from traditionally used plants.

In vitro evaluation of aconitine-induced arrhythmia based on RTCA Cardio technology / 中国药理学通报

Aim To establish an in vitro arrhythmia detection technique based on real-time cell analysis (RTCA) Cardio sys-tem with aconitine as a tool drug, and to provide a reliable method for the development of antiarrhythmic drugs. Methods The effects of aconitine on rat cardiac rhythm were detected by eight-channel physiological recorder at the level of whole animal. In vitro cultured cardiac myocytes, the inoculation density of cardiac myocytes was investigated by HTCA method, the effect of aconitine on cardiac beating was monitored by RTCA Cardio system, and the CI value, beating rate, amplitude and irregular rhythm of cardiac myocytes were analyzed. Results Eight-channel physiological recorder was used to detect the effects of aconitine on whole animals. The results showed that aconitine(50 mg • g"1) could induce arrhythmias such as ventricular tachycardia, ventricular fibrillation, shortened RR interval and increased heart rate. RTCA Cardio system showed that aconitine (2-8 p,M) could induce arrhythmias such as increased cardiac cell beating frequency, decreased beating amplitude and abnormal beating state in a dose-dependent manner. Conclusions RTCA Cardio system can rapidly, sensitively and accurately detect the arrhythmia induced by aconitine in cardiac myocytes, which provides methodological reference for the development of antiarrhythmic drugs.

Preparation and in vitro evaluation of folic acid-albumin nanoparticles co-loaded with paclitaxel and nanosilver / 中草药

Objective Paclitaxel and nanosilver were co-encapsulated into folic acid-albumin nanoparticles to increase the toxicity and uptake of the drug and improve the targeting ability of tumor that highly expressed folic acid (Fa) receptor. Methods The mean Fa binding number of bovine serum albumin (BSA) was determined by ultraviolet absorption method. The nanoparticles were prepared through self-assemble method and then its shape, partical size, Zeta potential, and encapsulation efficiency were characterized with the dynamic light scattering (DLS) and transmission electron microscope (TEM). In addition, the cellular uptake of nanoparticles and the in vitro anti-tumor effect of drug-loaded nanoparticles were investigated on the KB cells model of oral epithelial carcinoma. Results Ultraviolet absorption results showed that the average Fa binding number of Fa-BSA was 11. The nanoparticles were discrete and uniform spheres with the average size of (98.20 ± 3.58) nm and Zeta potential of (-39.90 ± 1.98) mV. Cellular uptake experiments showed that folate-modified albumin nanoparticles were more easily taken up by KB cells. Cytotoxicity and apoptosis assay indicated that the modification of folic acid and co-loaded nanosilver could increase the inhibition of tumor cell proliferation and promote KB cells apoptosis. Conclusion The prepared nanoparticles have small particle size and high encapsulation efficiency, which can enhance the ability of the nanoparticles to be uptaken and the toxicity of the drug-loaded nanoparticles against tumor cells.

Optimization and in vitro evaluation of TAT and PEG co-modified tilianin-loaded composite phospholipid liposomes / 中草药

Objective To optimize the preparation technology of transcription activator (TAT) and polyethylene glycols (PEG) co-modified tilianin-loaded composite phospholipid liposome (TAT & PEG tilianin CPL, T&PTCPL) and investigate its protective effect on cardiomyocytes. Methods The composite phospholipid liposome was prepared by thin film-ultrasonic method. A three- factor, three-level Box-Behnken experimental design was employed. The weight ratio of total phospholipid to tilianin (X1), the concentration of DSPE-PEG2000-TAT (X2), and hydration volume (X3) were observed. The encapsulation efficiency (Y1), particle size (Y2), and polydispersion coefficient (Y3) were evaluated to optimize optimal formula. In addition, hypoxia/reoxygenation model was established with Na2S2O4 in H9C2 cells. Superoxide dismutase (SOD) activity, malonaldehyde (MDA) level and release of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were assessed to evaluate the effect of T&PTCPL, meanwhile, the in vitro release rate (dynamic dialysis method) and absorption rate of tilianin and T&PTCPL in Caco-2 cell were examined. Results The optimal formula was as following: X1 = 20, X2 = 1.7%, and X3 = 3.2 mL; The encapsulation efficiency was (86.62 ± 2.51)%, particle size was (149.7 ± 8.2) nm and PDI was 0.15 ± 0.05. Compared with model group, T&PTCPL and tilianin groups increased SOD activity, inhibited level of MDA, LDH and CK-MB leakage (P < 0.05), and the effect of T&PTCPL group was better than tilianin group, meanwhile, T&PTCPL was completely released at 48 h, with a cumulative release of 88.65%, and Caco-2 cells had better absorption of T&PTCPL. Conclusion The Box-Behnken design is suitable for optimizing the formulation of T&PTCPL, and the observed responses are in close agreement with the predicted values of the mathematic models; Moreover, T&PTCPL shows a better sustained release effect in vitro release, which promots the absorption of tilianin in Caco-2 cells and suggests that T&PTCPL may have protective effect on myocardial ischemia reperfusion injury.

Preparation and characterization of reactive oxygen species-responsive Bletilla striata polysaccharide micelle / 中草药

Objective To prepare reactive oxygen species (ROS)-responsive Bletilla striata polysaccharide (Oxi-BSP) micelles, optimize their preparation technnology, and evaluate its in vitro characterizations. Methods Oxi-BSP was synthesized, then curcumin (Cur)-loaded micelles were prepared by a dialysis method. The formulation and preparation technology was optimized using an orthogonal design method. The morphology was observed by transmission electron microscope, while the particle size, particle distribution, and zeta potential were determined by laser particle size analyzer. Hydrogen peroxide was used to simulate the ROS environment and then the change of micellar morphology was observed. Results The Cur-loaded micelles were spherical with homogeneous distribution, the mean size was (225.33 ± 2.97) nm, the zeta potential was (-16.80 ± 0.37) mV, the encapsulation efficiencies was (85.75 ± 0.87)%, and drug loading capacities was (20.21 ± 0.44)%. And the micelles were responsive to ROS stimuli. Conclusion The obtained micelles display an uniform particle size distribution with moderate drug encapsulation efficiencies and drug loading capacities.

Preparation and in vitro evaluation of pH-responsive drug releasing As2O3-loaded PEG-PCL-PEI nanoparticles / 中草药

Objective To prepare and evaluate As2O3 loaded polyethylene glycol-polycaprolactone-polyethyleneimine (PEG-PCL- PEI, PPP) nanoparticles (As2O3-PPP-NPs) in vitro. Methods As2O3-PPP-NPs was prepared by one-step electrostatic loading method using PPP triblock polymer as carrier. The drug loading and entrapment efficiency of the nano-drug were determined by ICP-OES. In vitro drug release property was studied by the dialysis bag method. Hemolytic toxicity of As2O3-PPP-NPs was investigated by UV spectrophotometry. Cytotoxicity of As2O3-PPP-NPs on human cervical cancer (HeLa) and human hepatocellular carcinoma cells (HepG2) was evaluated by MTT assay. Finally, ICP-OES and confocal microscopy was used to investigate the uptake efficiency and uptake mechanism of As2O3-PPP-NPs by HepG2 cells. Results The prepared nano-formulations were spherical and well-dispersed with particle size of 88.7 nm. The encapsulation efficiency and the drug loading rate were (92.75 ± 3.83)% and (4.39 ± 0.26) %, respectively. In vitro release studies showed that As2O3-PPP-NPs had the characteristics of sustained release and low pH responsive drug release, which could achieve specific drug release in the tumor environment. The loading of As2O3 neutralized the positive charge of PPP, and the hemolytic toxicity of the material was reduced. MTT assay showed that the median lethal concentrations (IC50 values) of As2O3-PPP- NPs to HeLa and HepG2 cells were 6.24 μmol/L and 5.85 μmol/L, respectively, which showed strong inhibiting effect on tumor cells. Cellular uptake studies showed that As2O3-PPP-NPs was rapidly taken up by cells due to positively charged surface and featured the lysosomal escaping ability, so the drug could be released in the cytoplasm and exert its anti-tumor effect. Conclusion As2O3-PPP-NPs exhibits significantly sustained and low pH responsive release characteristics, and has the ability to escape from lysosomes. As2O3-PPP-NPs is a potential drug delivery system against solid tumor.

Endpoints for evaluating drug-induced liver injury in vitro and their application in detection systems / 中国药理学与毒理学杂志

Drug-induced liver injury (DILI) is a major cause of acute liver failure in clinic.Numerous emerging cell-based models and high-throughput screening technologies are being applied to hepato?toxicity evaluation in vitro.Before applying these emerging technologies and approaches,it is important to determine which endpoints should be included in the testing system to improve the predictive power of DILI. Based on the important mechanisms of DILI, this review introduces the endpoints that can be used for in vitro evaluation of DILI,such as hepatotoxicity,mitochondrial toxicity,cholestatic,liver injury caused by active metabolites,and immune-based liver injury.The application of these endpoints in DILI detection systems and the challenges in the application process are summarized so as to provide refer?ence for in vitro evaluation of hepatotoxicity in the early stage of new drug development.

Study on the Feasibility of Evaluating Drug in vitro Sustained Release Performance by Overflow Dissolu-tion Method / 中国药房

OBJECTIVE:To study the feasibility of overflow dissolution method for evaluating the drug in vitro sustained re-lease performance. METHODS:Overflow dissolution method was established by simulating the drugs elimination in vivo. Using Nifedipine sustained-elease tablets(Ⅰ)from 2 different manufacturers as model drug A,B,concentration-time curve,cumulative release rate- time curve,release velocity-time curve of model drugs in release pool at 3 different overflow speed (0,1.50,3.00 mL/min)were investigated. RESULTS:When overflow speed was 0,the cumulative dissolution was consistent with that of the con-ventional dissolution method. As the overflow speed increased,cmax of drug A,B was decreased [A:(8.89±0.20),(5.21±0.04), (3.51±0.03)μg/mL;B:(7.62±0.05),(4.80±0.09),(2.89±0.04)μg/mL];cumulative release rate was increased [A:(85.47± 2.45)%,(94.29 ± 2.44)%,(96.04 ± 2.56)%;B:(73.28 ± 1.13)%,(78.46 ± 1.94)%,(82.50 ± 1.69)%] ;tmax was ahead (A:1.5,1.0,0.5 h;B:2.0,1.0,0.5 h). CONCLUSIONS:Overflow dissolution method has avoided the inhibition of too large drug concentration on drug release,making complete drug release and more accurate evaluation of in vivo sustained release performance of the preparation.

Lupeol and its esters: NMR, powder XRD data and in vitro evaluation of cancer cell growth

ABSTRACT The triterpene lupeol (1) and some of its esters are secondary metabolites produced by species of Celastraceae family, which have being associated with cytotoxic activity. We report herein the isolation of 1, the semi-synthesis of eight lupeol esters and the evaluation of their in vitro activity against nine strains of cancer cells. The reaction of carboxylic acids with 1 and DIC/DMAP was used to obtain lupeol stearate (2), lupeol palmitate (3) lupeol miristate (4), and the new esters lupeol laurate (5), lupeol caprate (6), lupeol caprilate (7), lupeol caproate (8) and lupeol 3',4'-dimethoxybenzoate (9), with high yields. Compounds 1-9 were identified using FT-IR, 1H, 13C-NMR, CHN analysis and XRD data and were tested in vitro for proliferation of human cancer cell activity. In these assays, lupeol was inactive (GI50> 250µg/mL) while lupeol esters 2 -4 and 7 - 9 showed a cytostatic effect. The XRD method was a suitable tool to determine the structure of lupeol and its esters in solid state. Compound 3 showed a selective growth inhibition effect on erythromyeloblastoid leukemia (K-562) cells in a concentration-dependent way. Lupeol esters 4 and 9 showed a selective cytostatic effect with low GI50 values representing promising prototypes for the development of new anticancer drugs.

Research Progress in Experimental Methods for the Evaluation of Adhesion Property of Bioadhesive Drug Delivery Systems in vitro / 中国药师

Bioadhesive delivery systems with sustained release characteristics can promote the absorption and increase the bio-availability of drugs by prolonging the residence time on the applied site. The evaluation of adhesion property of bioadhesive drug deliv-ery systems is important because the sustained release effect and the absorption are closely related with the adhesion. The methods for the evaluation of the adhesive properties of bioadhesive drug delivery systems in vitro were summarized in the article, including determi-ning the minimum peel force, measuring the residues on mucosa surface, determining the retention time on mucosal surface, measuring the swelling and the viscosity of fluid and so on, and the operation of some methods were described simply as well.

Preparation and in vitro evaluation of dabigatran etexilate nanoemulsion / 中国药科大学学报

@#The purpose of this study was to prepare dabigatran etexilate nanoemulsion to improve bioavailability of dabigatran etexilate, a poorly water-soluble drug. The physicochemical properties and the stability of dabigatran etexilate nanoemulsion were investigated. Equilibrium solubility of dabigatran etexilate in commonly used oil materials for nanoemulsion were determined for selection. Then, surfactant and co-surfactant were chosen based upon the plooted pseudo-ternary diagrams. The formulation and preparation process were further optimized with orthogonal design. As a result, the dabigatran etexilate nanoemulsion was formulated based on the system consisting of Oil Acid/Labrafac Lipophile WL1394/Cremophor RH40/Transcutol P/H2O. The dabigatran etexilate nanoemulsion was found to have a mean diameter of(57. 5±0. 2)nm, Zeta potential of -(20. 9±1. 4)mV, and the drug encapsulation efficiency of(85. 2±1. 0)%. Besides, the droplet size, stability constant and drug content of the nanoemulsion was found to have no significant changes in at least 3 months under room temperature. In conclusion, the uniform and stable dabigatran etexilate nanoemulsion with a clear and translucent appearance was obtained after the optimization of formulation and preparation process. Thus nanoemulsion could be a promising way for the improvement of bioavailability of dabigatran etexilate and other poorly water-soluble drugs.

Physical chemistry evaluation of stability, spreadability, in vitro antioxidant, and photo-protective capacities of topical formulations containing Calendula officinalis L. leaf extract

Calendula is used widely in cosmetic formulations that present phenolic compounds in their chemical constitution. The objective of our research was to develop and evaluate the stability of topical formulations containing 5% hydro-ethanolic extract of calendula leaves, including spreadability, and in vitro photo-protective, and antioxidant capacity. To evaluate the stability, we used organoleptic characteristics, pH, and viscosity parameters. Antioxidant capacity was measured by the DPPH (2,2-diphenyl-1-picrylhydrazyl) method, and the photo-protective capacity by SPF spectrophotometric measure. All formulations were stable. The calendula extract formulations in gel and cream showed no significant variations in pH, and the cream formulations presented lower viscosity variations than gel formulations. The spreadability of the gel formulations was superior to those in cream. The formulations also presented good antioxidant capacities and an FPS of around 1.75. In accordance with the results, the formulations can be used as antioxidants, but considering the low SPF obtained, calendula cannot be considered as a stand-alone sunscreen, yet may well be tested in future studies towards verifying enhancement of synthetic sunscreens.

A calêndula é amplamente utilizada em formulações cosméticas, apresentando compostos fenólicos em sua constituição química. Desta forma, o objetivo desta pesquisa foi desenvolver e avaliar a estabilidade de formulações tópicas contendo 5% de extrato hidroetanólico das folhas de calêndula, bem como a espalhabilidade, capacidade antioxidante e fotoprotetora in vitro nas mesmas. Para a avaliação da estabilidade, foram usados parâmetros como a verificação das características organolépticas, pH e viscosidade. A capacidade antioxidante foi verificada pelo método do DPPH (2,2-difenil,1- picril-hidrazila) e a capacidade fotoprotetora pela medida espectrofotométrica do FPS. Para as formulações testadas, observou-se que apresentaram uma boa estabilidade. As formulações de creme e gel com extrato de calêndula não apresentaram variações significativas nos valores de pH e o creme apresentou as menores variações de viscosidade em relação ao gel. A espalhabilidade das formulações de gel foi superior à do creme. As formulações também apresentaram uma boa capacidade antioxidante e um FPS em torno de 1.75. De acordo com os resultados, a formulação pode ser utilizada com ação antioxidante, porém com o FPS obtido, a calêndula não pode ser considerada um filtro solar isolado, mas poderá ser testada em estudos futuros para verificar a potencialização de filtros solares sintéticos.