To evaluate the effects of Hydroxypropyl methylcellulose acetate succinate(HPMCAS MF) on absorption of silybin(SLB) from supersaturable self-nanoemulsifying drug delivery system which was pre-prepared at the early stage experiment. The cell toxicity of self-emulsifying preparation was evaluated by the MTT method, and the in vitro membrane permeability and absorption promoting effect of the self-emulsifying preparation were evaluated by establishing a Caco-2 cell monolayer model. The in vivo and in vitro supersaturation correlation was evaluated via the blood concentration of SLB. The results of MTT showed that the concentration of the preparation below 2 mg·mL~(-1)(C_(SLB) 100 μg·mL~(-1)) was not toxic to Caco-2 cells, and the addition of polymer had no significant effect on Caco-2 cells viability. As compared with the solution group, the transport results showed that the P_(app)(AP→BL) of the self-emulsifying preparation had a very significant increase; the transport rate of silybin can be reduced by polymer in 0-30 min; however, there was no difference in supersaturated transport between supersaturated SLB self-nanoemulsion drug delivery system(SLB-SSNEDDS) and SLB self-nanoemulsion drug delivery system(SLB-SNEDDS) within 2 hours. As compared with SLB suspension, pharmacokinetic parameters showed that the blood concentration of both SLB-SNEDDS and SLB-SSNEDDS groups were significantly increased, and C_(max) was 5.25 times and 9.69 times respectively of that in SLB suspension group, with a relative bioavailability of 578.45% and 1 139.44% respectively. C_(max) and relative bioavailability of SLB-SSNEDDS were 1.85 times and 197% of those of SLB-SNEDDS, respectively. Therefore, on the one hand, SSNEDDS can increase the solubility of SLB in gastrointestinal tract by maintaining stability of SLB supersaturation state; on the other hand, the osmotic transport process of SLB was regulated through the composition of its preparations, and both of them could jointly promote the transport and absorption of SLB to improve the oral bioavailability of SLB.
Administration, Oral ; Biological Availability ; Caco-2 Cells ; Drug Delivery Systems ; Emulsions ; Humans ; Methylcellulose/analogs & derivatives* ; Nanoparticles ; Particle Size ; Silybin ; Solubility

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.
Chemistry, Pharmaceutical ; Curcumin ; chemistry ; Drug Stability ; Methylcellulose ; analogs & derivatives ; chemistry ; Polymers ; Solubility

Canine mammary tumors are among the most frequently observed cutaneous tumors in female dogs. Cancer stem cells (CSCs), referred to as tumor-initiating cells, are thought to have properties similar to normal stem cells such as the ability to self-renewal and to differentiate into various cell types. Biological understanding of CSCs and the critical pathways involved in their maintenance are important in research and therapy for mammary tumors. We conducted the present study on sphere formation from REM134 cells by using methylcellulose to produce tumorspheres on a large scale and compared the specific markers of the spheres-formed and plating-cultured REM134 cells. The results revealed that the tumorspheres cultured in methylcellulose had higher seeding density and improved morphology compared to those produced in normal sphere formation medium. Expression levels of stemness markers and CSC-related markers were higher in tumorsphere-forming cells than in plating-cultured cells. Subsequently, we transplanted the tumorsphere-forming and plating-cultured cells into female nude mice to examine their tumorigenic potential. Tumor volume increased rapidly in mice transplanted with tumorsphere-derived cells compared to plating-cultured cells. We observed a novel sphere-forming condition for REM134 cells and showed that REM134 cell tumorspheres can exhibit improved CSC properties.
Animals ; Carcinogenesis ; Critical Pathways ; Dogs ; Female ; Humans ; Mammary Neoplasms, Animal ; Methylcellulose ; Mice ; Mice, Nude ; Neoplastic Stem Cells ; Stem Cells ; Tumor Burden

The present study investigated risk factors for iron deficiency (ID) and iron deficiency anemia (IDA) during late infancy, including feeding type and complementary feeding (CF) practice. Healthy term Korean infants (8–15 months) were weighed, and questionnaires regarding delivery, feeding, and weaning were completed by their caregivers. We also examined levels of hemoglobin, serum iron/total iron-binding capacity, serum ferritin, and mean corpuscular volume (MCV). Among 619 infants, ID and IDA were present in 174 infants (28.1%) and 87 infants (14.0%), respectively. The 288 infants with exclusively/mostly breastfeeding until late infancy (BFL) were most likely to exhibit ID (53.1%) and IDA (28.1%). The risk of ID was independently associated with BFL (adjusted odds ratio [aOR], 47.5; 95% confidence interval [CI], 18.3–122.9), male sex (aOR, 1.9; 95% CI, 1.2–2.9), fold weight gain (aOR, 2.6; 95% CI, 1.5–4.6), and perceived inadequacy of red meat intake (aOR, 1.7; 95% CI, 1.0–2.7). In addition to the risk factors for ID, Cesarean section delivery (aOR, 1.9; 95% CI, 1.1–3.2) and low parental CF-related knowledge (aOR, 2.8; 95% CI, 1.5–5.2) were risk factors for IDA. In conclusion, prolonged breastfeeding and perceived inadequacy of red meat intake may be among the important feeding-related risk factors of ID and IDA. Therefore, more meticulous education and monitoring of iron-rich food intake, such as red meat, with iron supplementation or iron status testing during late infancy if necessary, should be considered for breastfed Korean infants, especially for those with additional risk factors for ID or IDA.
Anemia, Iron-Deficiency ; Breast Feeding* ; Caregivers ; Cesarean Section ; Eating ; Education ; Erythrocyte Indices ; Female ; Ferritins ; Humans ; Infant Nutritional Physiological Phenomena ; Infant* ; Iron* ; Male ; Methylcellulose ; Odds Ratio ; Parents ; Pregnancy ; Red Meat* ; Risk Factors ; Weaning ; Weight Gain

The present study was designed to prepare and compare bio-adhesive pellets of panax notoginseng saponins (PNS) with hydroxy propyl methyl cellulose (HPMC), chitosan, and chitosan : carbomer, explore the influence of different bio-adhesive materials on pharmacokinetics behaviors of PNSbio-adhesive pellets, and evaluate the correlation between in vivo absorption and in vitro release (IVIVC). In order to predict the in vivo concentration-time profile by the in vitro release data of bio-adhesive pellets, the release experiment was performed using the rotating basket method in pH 6.8 phosphate buffer. The PNS concentrations in rat plasma were analyzed by HPLC-MS-MS method and the relative bioavailability and other pharmacokinetic parameters were estimated using Kinetica4.4 pharmacokinetic software. Numerical deconvolution method was used to evaluate IVIVC. Our results indicated that, compared with ordinary pellets, PNS bio-adhesive pellets showed increased oral bioavailability by 1.45 to 3.20 times, increased C, and extended MRT. What's more, the release behavior of drug in HPMC pellets was shown to follow a Fickian diffusion mechanism, a synergetic function of diffusion and skeleton corrosion. The in vitro release and the in vivo biological activity had a good correlation, demonstrating that the PNS bio-adhesive pellets had a better sustained release. Numerical deconvolution technique showed the advantage in evaluation of IVIVC for self-designed bio-adhesive pellets with HPMC. In conclusion, the in vitro release data of bio-adhesive pellets with HPMC can predict its concentration-time profile in vivo.
Acrylic Resins ; Adhesives ; Animals ; Chitosan ; Drug Carriers ; Drug Liberation ; In Vitro Techniques ; Intestinal Absorption ; Male ; Methylcellulose ; Panax notoginseng ; chemistry ; Plant Extracts ; administration & dosage ; metabolism ; pharmacokinetics ; Rats, Sprague-Dawley ; Saponins ; administration & dosage ; metabolism ; pharmacokinetics

Sparassis crispa is an edible mushroom with various medicinal properties. Here we demonstrate the effect of Sparassis crispa on carbon tetrachloride (CCl4)-induced hepatotoxicity and the underlying mechanism. To evaluate the hepatoprotective effects of Sparassis crispa ethanol extract (SCE), 50 male Sprague-Dawley rats were equally divided into 5 groups. Group I is the normal control rats with an intraperitoneal (i.p.) 0.5% carboxy methyl cellulose (CMC) pretreatment and olive oil treatment. Group II is the model group with an i.p. 0.5% CMC and 0.5 mL/kg CCl4 treatment. Group III and IV is the CCl4-administered rats pretreated with an i.p. 100 and 200 mg/kg SCE, respectively. Group V includes the silymarin group with an i.p. 50 mg/kg silymarin and CCl4 treatment. At 16 h after the CCl4 treatment, the levels of serum aminotransferases, TNF-alpha, and lipid peroxidation were substantially increased, whereas the activity of hepatic antioxidative enzymes, such as superoxide dismutase and catalase, was decreased. These changes were attenuated by SCE. The histological studies also showed that SCE inhibited the CCl4-induced liver injury. Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were elevated after CCl4 treatment, while the cytochrome P450 2E1 (CYP2E1) expression was suppressed. SCE treatment inhibited the formation of liver nitrite, reduced the over-expression of iNOS and COX-2 proteins, but restored the liver CYP2E1 content compared with the CCl4-treated model group. The present data elucidate that SCE protects the liver against CCl4-induced acute hepatotoxicity, which might be due to its ability to restore the CYP2E1 function and suppress the inflammatory responses, in combination with its capacity to reduce oxidative stress.
Agaricales ; Animals ; Carbon Tetrachloride ; Carbon* ; Catalase ; Cyclooxygenase 2 ; Cytochrome P-450 CYP2E1 ; Ethanol ; Humans ; Lipid Peroxidation ; Liver ; Male ; Methylcellulose ; Nitric Oxide Synthase Type II ; Olea ; Oxidative Stress ; Rats* ; Rats, Sprague-Dawley ; Silymarin ; Superoxide Dismutase ; Transaminases ; Tumor Necrosis Factor-alpha ; Olive Oil

BACKGROUND: The number of CD34+ cells in a peripheral blood stem cell collection is the key factor in predicting successful treatment of hematologic malignancies. Korean Red Ginseng (KRG) (Panax ginseng C.A. Meyer) is the most popular medicinal herb in Korea. The objective of this study was to determine the effect of KRG on hematopoietic colony formation. METHODS: Bone marrow (BM) samples were obtained from 8 human donors after acquiring informed consent. BM mononuclear cells (MNCs) were isolated, and CD34+ cells were sorted using magnetic beads. The sorted CD34+ cells were incubated with or without total extract of KRG (50 microg/mL, 100 microg/mL) or Ginsenoside Rg1 (100 microg/mL), and the hematopoietic colony assay was performed using methylcellulose semisolid medium. The CD34+ cell counts were measured by a single platform assay using flow cytometry. RESULTS: The numbers of human BM-MNCs and CD34+ cells obtained after purification were variable among donors (5.6x10(7) and 1.3-48x10(7) and 8.9x10(4) and 1.8-80x10(4), respectively). The cells expanded 1,944 times after incubation for 12 d. Total extract of KRG added to the hematopoietic stem cell (HSC)-specific medium increased CD34+ cell counts 3.6 times compared to 2.6 times when using HSC medium alone. Total numbers of hematopoietic colonies in KRG medium were more than those observed in conventional medium, especially that of erythroid colonies such as burst forming unit-erythroid. CONCLUSION: Total extract of KRG facilitated CD34+ cell expansion and hematopoietic colony formation, especially of the erythroid lineage.
Antigens, CD34 ; Bone Marrow* ; Cell Count ; Flow Cytometry ; Hematologic Neoplasms ; Hematopoietic Stem Cells ; Humans ; Informed Consent ; Korea ; Medicine, Korean Traditional ; Methylcellulose ; Panax* ; Plants, Medicinal ; Stem Cells ; Tissue Donors

OBJECTIVE: Systemic sclerosis is a connective tissue disease characterized by vasculopathy, excessive accumulation of extracellular matrix, and fibrosis of the skin and internal organs. The dietary flavonoid apigenin has been shown to reduce expression of the myofibroblast phenotype and to inhibit contraction of collagen gels. We investigated the effect of apigenin on the prevention and treatment of a modified bleomycin-induced animal model of scleroderma. METHODS: Recently, we successfully induced scleroderma by weekly subcutaneous injections of bleomycin using a thermo-reversible combination gel composed of low molecular weight methylcellulose. A weekly subcutaneous injection of methylcellulose gel loaded with bleomycin induced focal skin fibrosis on the back skin and fibrotic phenotype of lung tissue in mice. The histologic examination of skin and lungs, collagen assay of lungs, and expression of connective tissue growth factor were investigated. RESULTS: Daily intra-peritoneal injection of 1.0 mg/kg or 2.5 mg/kg of apigenin starting a week before the bleomycin injections failed to prevent the development of skin fibrosis and reduce the fibrotic phenotypes of skin and lung tissue. CONCLUSION: Although some in vitro experiments have supported a potential role of apigenin in the treatment of fibrosis, dietary flavonoid apigenin is not effective in preventing development of a bleomycin-induced murine model of scleroderma.
Animals ; Apigenin ; Bleomycin ; Collagen ; Connective Tissue Diseases ; Connective Tissue Growth Factor ; Contracts ; Extracellular Matrix ; Fibrosis ; Gels ; Injections, Subcutaneous ; Lung ; Methylcellulose ; Mice ; Models, Animal ; Molecular Weight ; Myofibroblasts ; Phenotype ; Scleroderma, Systemic ; Skin

OBJECTIVEUsing Apocynum venetum as a model drug to prepare pulsed-release tablets based on diffusion, swelling, osmotic pressure mechanism and to evaluate the release characteristics.

METHODThe pulsatile release tablets were prepared by film coating methods using HPMC E5 and Eudragit The effect of formulation on pulsatile release of A. venetum was investigated.

RESULTThe pulsed-release tablet was prepared by a swelling layer coating which contains HPMC E5 and a controlled-release membrane containning Eudragit. The delayed release time of the tablets was (5.0 +/- 0.5) h.

CONCLUSIONThe pulsatile release characteristics of A. venetum pulsatile release tablets were confirmed in vitro.

Apocynum ; chemistry ; Delayed-Action Preparations ; chemistry ; Diffusion ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; chemistry ; In Vitro Techniques ; Lactose ; analogs & derivatives ; analysis ; Methylcellulose ; analogs & derivatives ; analysis ; Osmotic Pressure ; Plant Leaves ; chemistry ; Polymethacrylic Acids ; analysis ; Solubility ; Tablets ; chemistry ; Time Factors

Poloxamer F127, poloxamer F68 and hydroxypropyl methylcellulose K4M were used to prepare the thermosensitive in situ gel of boanmycin hydrochloride for injection. Its gelation temperature, rheological behavior, texture characteristics, scanning electron microscopy, in vitro and in vivo drug release were evaluated. These results showed that the formulation was a fluid solution at room temperature, which could become semisolid at the temperature of 37 degrees C, and the thermally induced sol-gel transition allowed to be injectable and in situ setting. The formulation was constructed into a tridimensional network at gelation temperature. The drug release was controlled by the diffusion of the drug and the erosion of the gelmatrix. The pharmacokinetics indicated that the drug could be released slowly for up to 48 hours after subcutaneous administration in rats.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Bleomycin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Diffusion ; Drug Delivery Systems ; Gels ; Hypromellose Derivatives ; Injections, Subcutaneous ; Male ; Methylcellulose ; analogs & derivatives ; chemistry ; Microscopy, Electron, Scanning ; Poloxamer ; chemistry ; Rats ; Rats, Sprague-Dawley ; Rheology ; Temperature ; Viscosity