Effects of HPMCAS MF on absorption of silybin from supersaturable self-nanoemulsifying drug delivery system / 中国中药杂志

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.

Effect of HPMCAS/curcumin amorphous solid dispersion in enhancing dissolution and chemical stability of curcumin / 中国中药杂志

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.

Tumorsphere formation and cancer stem cell characterization of REM134 canine mammary carcinoma cells / 대한수의학회지

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.

Physical properties and biological effects of mineral trioxide aggregate mixed with methylcellulose and calcium chloride

Abstract Objectives: Methylcellulose (MC) is a chemical compound derived from cellulose. MTA mixed with MC reduces setting time and increases plasticity. This study assessed the influence of MC as an anti-washout ingredient and CaCl2 as a setting time accelerator on the physical and biological properties of MTA. Material and Methods: Test materials were divided into 3 groups; Group 1(control): distilled water; Group 2: 1% MC/CaCl2; Group 3: 2% MC/CaCl2. Compressive strength, pH, flowability and cell viability were tested. The gene expression of bone sialoprotein (BSP) was detected by RT-PCR and real­ time PCR. The expression of alkaline phosphatase (ALP) and mineralization behavior were evaluated using an ALP staining and an alizarin red staining. Results: Compressive strength, pH, and cell viability of MTA mixed with MC/CaCl2 were not significantly different compared to the control group. The flowability of MTA with MC/CaCI2 has decreased significantly when compared to the control (p<.05). The mRNA level of BSP has increased significantly in MTA with MC/CaCl2 compared to the control (p<.05). This study revealed higher expression of ALP and mineralization in cells exposed to MTA mixed with water and MTA mixed with MC/CaCl2 compared to the control (p<.05). Conclusions: MC decreased the flowability of MTA and did not interrupt the physical and biological effect of MTA. It suggests that these cements may be useful as a root-end filling material.

Salivary stimulation by prolonged release of pilocarpine in sjõgren’ syndrome

Introduction: Prolonged drug delivery in the oral cavity offers many advantages, such as reducing adverse effects. Pilocarpine is an FDA-approved parasympathomimetic drug for the treatment of glandular hypofunction; however, its adverse effects limit its use. Objective: To evaluate the stimulation of salivary flow by the use of pilocarpine-releasing films, as well as their effects on the symptoms of xerostomia and adverse effects in patients with Sjõgren’s syndrome (SS). Materials and methods: Hydroxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. The pH and thickness, as well as diffusion uniformity and kinetics of drug release per cm2 were evaluated by spectrophotometry. The films were tested sublingually in 40 patients with Sjõgren’s syndrome for a period of two weeks. Changes in their salivary flow were evaluated by analyzing samples of total saliva. Additionally, patients were screened for symptoms of xerostomia and adverse effects. Results: The films had a pH of 2.91 +/- 0.035, a thickness of 0.06866 +/- 0.00152μm, and a diffusion uniformity of 91 percent per cm2. Use of the films resulted in an increase in salivary flow in both primary and secondary Sjõgren’s syndrome, but this increase was only significant in primary SS. Conclusion: Films showed optimal physicochemical properties for their administration, and proved effective in stimulating salivary flow without causing adverse effects during their administration.

Avaliação da eficácia de um novo marcador cirúrgico para capsulorrexe anterior / Effectiveness evaluation of a new surgical marker for anterior capsulorhexis

RESUMO Objetivo: Avaliar a eficácia de um novo marcador cirúrgico para ajudar na confecção da capsulorrexe anterior analisando o seu dimensionamento e formato, comparando com a capsulorrexe confeccionada manualmente de maneira livre. Métodos: Como experimento, 3 residentes (R3) de Oftalmologia do Hospital Universitário Onofre Lopes (HUOL) e 1 oftalmologista em treinamento, voluntários, realizaram (cada um) 10 capsulorrexes em olhos de porco enucleados. Em 5 olhos foi utilizado o marcador e em outros 5, não. Todos os olhos foram fotografados tendo ao lado uma régua para orientar e calibrar um aplicativo para a avaliação morfométrica do procedimento. O diâmetro alvo foi de 5 mm, cujo perímetro correspondente é 15,7 mm e a área 19,652 mm2. Foram avaliados em cada procedimento: os diâmetros máximo, mínimo e médio, o perímetro, a área e o desvio em relação ao diâmetro e quanto ao aspecto ideal. Resultados: No grupo utilizando o marcador o diâmetro médio foi 5,44mm (±0,89) contra 6,37mm (±0,67) (p=0,001), no grupo no qual não se utilizou o marcador; quanto ao perímetro, 17,52mm (±1,92) no grupo utilizando o marcador contra 20,14mm (±2,09) (p<0,001) sem o marcador e quanto a área, 24,73mm2 (±1,92) com o marcador, contra 32,62mm2 (±6,32) (p<0,001), sem o marcador. Em relação ao aspecto da capsulorrexe 1,26mm (±0,12), contra 1,21mm (±0,7) (p=0,09) e em relação ao desvio de curvatura: 0,87 (±0,05), contra 0,9 (±0,04), (p=0,06) respectivamente. Conclusão: O trabalho mostrou que o marcador avaliado é eficaz para auxiliar a confecção da capsulorrexe conduzindo a resultados melhores que o método a mão livre.

ABSTRACT Purpose: To evaluate the effectiveness of a surgical device that intented to help in the preparation of the anterior capsulorhexis analyzing the design and shape, comparing with capsulorhexis made by free hand. Methods: Three ophthalmology residents(R3) at the HUOL and one surgeon in training, participate in this research as volunteers. Each surgeon perform 5 capsulorhexis in porcine eyes using the device, and five others by free hand as a control. All capsulorhexis were photographed having a ruler as reference to guide and calibrate a computer application for morphometric evaluation (Cambuí Labs, Natal, Brazil). All surgeons aimed to produce a circular continuous capsulorhexis of 5 mm diameter that represents 15,7mm in perimeter and 19,652mm2 in area. Each wet-lab capsulorhexis was evaluated in regard to these criteria: diameter (mean, maximum and minimum), perimeter, area, deviation from the ideal diameter and ideal shape. Results: Compare to control groups, capsulorhexis with the aid of the surgical device showed: 5,44mm ±0,89 vs 6,37mm ±0,67, for capsulorhexis diameter (p=0,001); 17,52mm ±1,92 vs 20,14mm ±2,09 for capsulorhexis perimeter (<0.001); 24,73mm2 ±1,92 vs 32,62mm2 ±6,36 for capsulorhexis area (p<0,001). A tendency for better result with the aid of the surgical device was observed for deviation of an ideal diameter or ideal aspect were appreciated: 0,87mm ±0,05 vs 0,9 ±0,04 for deviation of a curve (p=0,06); 1,26mm ±0,12 vs 1,21mm ±0,7 for the capsulorhexis aspect (p=0,09). Conclusion: Capsulorhexis produced with the aid of the surgical device, significantly improved wet-lab capsulorhexis performance.

Pharmacokinetics and correlation between in vitro release and in vivo absorption of bio-adhesive pellets of panax notoginseng saponins / 中国天然药物

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.

Breastfeeding and Red Meat Intake Are Associated with Iron Status in Healthy Korean Weaning-age Infants

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.

Safety and feasibility of the use of a bevacizumab-methylcellulose mixture as an adjunct to glaucoma surgery: a pilot study / Segurança e viabilidade do uso de uma mistura de bevacizumabe-metilcelulose como terapia adjuvante à cirurgia anti-glaucomatosa: um estudo piloto

ABSTRACT Bevacizumab, a monoclonal anti-vascular endothelial growth factor antibody, has been suggested as a potential healing therapeutic following glaucoma surgery. Here, we aimed to improve the bioavailability of bevacizumab when used as an adjunct therapy to non-penetrating deep sclerectomy (DS) by using a bevacizumab-methylcellulose mixture (BMM). Ten previously non-operated eyes in ten patients diagnosed with primary open angle glaucoma underwent DS with a subconjunctival injection of 0.3 ml of BMM (bevacizumab 3.75 mg incorporated into 4% methylcellulose) at the surgical site. Bevacizumab release was evaluated in vitro using size-exclusion high performance liquid chromatography (HPLC). Intraocular pressure (IOP), bleb morphology, corneal endothelial cell count (CECC), and complications were evaluated at 6 months after surgery. Using HPLC, bevacizumab was detected in BMM for up to 72 h. Moreover, all surgical blebs remained expanded with hyaline material during the first week. A significant IOP reduction (mean ± SD= -10.3 ± 5.4 mmHg, P<0.001) and diffuse blebs were observed at the final follow-up period. Although CECC was slightly reduced (-7.4%), no complications were observed. In conclusion, bevacizumab was released from BMM, and the use of this innovative mixture yielded good results following DS with no complications. Further studies are required to determine its efficacy prior to establishing BMM as an adjunct treatment for penetrating and non-penetrating glaucoma surgeries.

RESUMO O bevacizumabe (um agente anti-fator de crescimento endotelial vascular) tem sido sugerido como potencial modulador cicatricial na cirurgia do glaucoma. Este estudo objetivou melhorar a biodisponibilidade do bevacizumabe, investigando a viabilidade de uma nova mistura de bevacizumabe-metilcelulose (BMM) como terapia adjuvante para a esclerectomia profunda não-penetrante (DS). Dez olhos sem cirurgias prévias de 10 pacientes com glaucoma primário de ângulo aberto foram submetidos à DS associada à uma injeção subconjuntival de 0,3 ml da mistura de bevacizumabe-metilcelulose (bevacizumabe 3,75 mg incorporado em metilcelulose 4%) no sítio cirúrgico. A liberação de bevacizumabe foi avaliada in vitro através de cromatografia líquida de alta performance por exclusão de tamanho (HPLC). A pressão intraocular (PIO), a morfologia da ampola de filtração, a contagem de células endoteliais da córnea (CECC) e as complicações foram estudadas aos seis meses de seguimento. O bevacizumabe foi detectado a partir da mistura de bevacizumabe-metilcelulose por meio do HPLC até 72 horas. Além disso, todas as ampolas cirúrgicas permaneceram expandidas com material hialino durante a primeira semana. Uma redução significativa da pressão intraocular (média ± DP= -10,3 ± 5,4 mmHg, P<0,001) e ampolas difusas foram observadas ao final do período de seguimento. Embora a contagem de células endoteliais da córnea se mostrou discretamente diminuída (-7,4%), nenhuma complicação foi observada. Neste estudo, o bevacizumabe foi liberado da mistura de bevacizumabe-metilcelulose e o uso desta nova mistura se associou com bons resultados cirúrgicos e nenhuma complicação. Estudos futuros serão necessários para determinar sua eficácia, antes de se estabelecer a mistura de bevacizumabe-metilcelulose como um tratamento adjuvante às cirurgias penetrantes e não-penetrantes para o glaucoma.

Physicochemical and antimicrobial evaluation of chitosan and hydroxypropyl methylcellulose films forprolonged release of pilocarpine / Evaluación fisico-química y antimicrobiana de biopelículas de quitosán e hidroxipropilmetilcelulosa para liberación prolongada de pilocarpina

The use of prolonged local drug delivery to the oral cavity offers multiple benefits, such as increasing the pharmacological action in the desirable local site and reducing the usual dose and the adverse effects. Pilocarpine is a cholinergic drug approved by the FDA for the treatment of glandular hypofunction; however, the extent of its adverse effects limits its use. Objective: The main aim of this study was to analyze the physical and chemical properties of films, including pH, thickness, solubility, consistency and the ability to release pilocarpine for a prolonged time. Additionally, theantimicrobial activity in two opportunistic pathogens in hyposialia (Streptococcus mutans and Candida albicans) was also assessed. Methodology: Chitosan and HPMC (Methocel K4M CR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. PH, thickness and time of solubility in artificial saliva, as well as diffusion and drug release kinetics per cm2 (OD=420nm) were assessed by spectrophotometry. The antimicrobialactivity was tested by disk diffusion test against St. mutans ATCC 700610 and C. albicans ATCC 90029 at concentrations of hyposalivation (1.44x1.2x106 CFU and 103 CFU, respectively). Results: All the films, except for Hydroxypropyl methylcellulose / Pilocarpine formulation, were found to have optimal physical-chemical properties for handling, maintaining drug diffusion in 76 percent per cm2 for four hours extended-release without showing antimicrobial activity at concentrations of hyposalivation. Conclusion: The films had optimum handling properties and a constant drug release; however, antimicrobial activity was not found...

El uso local de administración prolongada de fármacos en la cavidad oral proporciona múltiples ventajas, aumentando la acción farmacológica en el sitio local deseable, reducción de la dosis usual y disminución de los efectos adversos. La pilocarpina es una droga colinérgica aprobada por la FDA para el tratamiento de la hipofunción glandular, sin embargo la amplitud de sus efectos adversos limitan su uso. Objetivo: Con el objetivo de analizar las propiedades físico-químicas de las biopelículas se evaluó el pH, grosor, solubilidad, uniformidad y la capacidad de liberar prolongadamente pilocarpina, así como su actividad antimicrobiana ante los dos microorganismos patógenos oportunistas en la hiposialia (Streptococcus mutans y Candida albicans). Metodología: Se elaboraron biopelículas de Quitosán e Hidroxipropilmetilcelulosa (Methocel K4MCR) en ácido acético al 1 por ciento, adicionadas con pilocarpina bajo agitación magnética, evaluando el pH, grosor y el tiempo de solubilidad en saliva artificial, así como la uniformidad de difusión y cinética de liberación de la droga por cm2 mediante espectrofotometría (OD=420nm). Mediante difusión en disco se evaluó la actividad antimicrobiana ante Streptococcus mutans ATCC 700610 y Candida albicans ATCC 90029 en concentraciones encontradas en hiposalivación (1.44 x 106 UFC y 1.2 x 103 UFC respectivamente). Resultados: Todas las biopelículas, a excepción de la formulación Hidroxipropilmetilcelulosa e Hidroxipropilmetilcelulosa/ Pilocarpina resultaron tener las propiedades físico-químicas óptimas de manipulación, manteniendo una uniformidad de difusión de la droga en 76 por ciento por cm2 con liberación prolongada por 4 horas, sin mostrar actividad antimicrobiana en concentraciones de hiposalivación. Conclusión: Las películas obtuvieron las propiedades óptimas de manipulación, y una constante liberación del fármaco, sin embargo, ninguna formulación presentó actividad antimicrobiana...

Total extract of Korean red ginseng facilitates human bone marrow hematopoietic colony formation in vitro

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.

Sparassis crispa Attenuates Carbon Tetrachloride-Induced Hepatic Injury in Rats / 체질인류학회지

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.

Optimization of sustained release matrix tablet of metoprolol succinate using central composite design

The present study was performed to optimize the formulation of metoprolol succinate [MS] sustained release tablets using hydroxypropyl methylcellulose [HPMC] and sodium alginate [SA] as the matrix combination. After investigating the effects of various parameters on drug release, a 2-factor, 5-level central composite design was employed, using the amount of HPMC K4M [A] and SA [318 cP] [B] as the independent variables and the drug percentage released at 1h, 4h, 8h, 20h [Q[1], Q[4], Q[8], Q20]] as the responses. Response surfaces were established to obtain the matrix ranges and the main factors affecting four responses. In order to validate the optimization study, six confirmatory runs were performed; indicating high predictability of response surface methodology for MS sustained release tablets. Data fitting to Peppas equation indicated that the mechanism of drug release could be diffusion along with erosion. This matrix combination can be used as a good alternative to the commercially pellet technology, which was complicated, time-consuming and energy-intensive

Formulation and in vitro evaluation of nateglinide microspheres using HPMC and carbopol-940 polymers by ionic gelation method

This study involves the design and characterization of Nateglinide [NAT] microspheres to enhance patient compliance. Ionic gelation technique was used to prepare Nateglinide Microspheres by using rate controlling polymers Carbopol-940 and Hydroxypropylmethyl cellulose [HPMC]. Shape and surface were evaluated with Scanning electron microscopy [SEM]. Percentage Yield, Particle size analysis, Encapsulating Efficiency, Micromeritic analysis, Fourier Transform Infra-Red Spectroscopy [FTIR], Differential Scanning Colorimetry [DSC] were done for characterization of Microspheres. Drug release studies were performed at pH 1.2 and 7.2 using USP dissolution type-2 apparatus and release rates were analyzed by the application of different pharmacokinetic models. The size of microspheres was found to be varied from 781 Micro m to 853 Micro m. Rheological studies proved excellent flow behavior while percentage yield was found to be varied from 72% to 79%. Absence of drug-polymers interactions was confirmed from FTIR and DSC results. The microspheres prepared with sodium alginate showed cracks while microspheres obtained from blend of Carbopol-940 plus sodium alginate were smooth and spherical. Maximum entrapment efficiency [71.4%] was achieved for Microspheres with Carbopol-940. The greater retardation in drug release was observed for microspheres containing Carbopol-940 and release pattern followed Higuchi kinetics model and negligible drug release was observed at pH 1.2

Formulation development and evaluation of diltiazem HCl sustained release matrix tablets using HPMC K4M and K100M

The aim of this study was to develop a sustained release hydrophilic matrix tablet of Diltiazem HCl and evaluates the effect of formulation variables [e.g. lubricant, binder, polymer content and viscosity grades of HPMC] on drug release. Twelve different formulations [F1-F12] were prepared by direct compression. The results of the physical parameters and assay were found to be within the acceptable range. Rate of drug release was found to be slow as the fraction of the polymer was increased from 20-50%. The drug release rate from tablets containing K4M was effectively controlled by increasing the talc concentration, whereas the burst effect was reduced by increasing binder content. The drug release was higher with K4M as compare to K100M. Model-dependent and independent methods were used for data analysis and the best results were observed for K4M in Higuchi [R[2]=0.9903-0.9962] and K100M in Baker and Lonsdale [R[2]=0.9779-0.9941]. The release mechanism of all formulations was non-Fickian. F7 [50% K4M, 2% talc, 10% Avicel PH101] and F11 [40% K100M] were very close to targeted release profile. F12 [50% K100M] exhibited highest degree of swelling and lowest erosion. The f[1] and f[2] test were performed taking F11 as a reference formulation

A clinical comparison between DisCoVisc and 2% hydroxypropylmethylcellulose in phacoemulsification: a fellow eye study

OBJECTIVE: This study sought to compare the effects and outcomes of two ophthalmic viscosurgical devices, 1.6% hyaluronic acid/4.0% chondroitin sulfate and 2.0% hydroxypropylmethylcellulose, during phacoemulsification. METHODS: This prospective, randomized clinical trial comprised 78 eyes (39 patients) that received phacoemulsification performed by the same surgeon using a standardized technique. Patients were randomly assigned to receive either 1.6% hyaluronic acid/4.0% chondroitin sulfate or 2.0% hydroxypropylmethylcellulose on the first eye. The other eye was treated later and received the other viscoelastic agent. Preoperative and postoperative examinations (5, 24 and 48 hours; 7 and 14 days; 3 and 6 months) included measurements of the total volume of the ophthalmic viscosurgical device, ultrasound and washout times to completely remove the ophthalmic viscosurgical device, intraocular pressure, central corneal thickness and best-corrected visual acuity. The corneal endothelial cell count was measured at baseline and at six months postoperatively. ClinicalTrials.gov: NCT01387620. RESULTS: There were no statistically significant differences between groups in terms of cataract density or ultrasound time. However, it took longer to remove 2.0% hydroxypropylmethylcellulose than 1.6% hyaluronic acid/ 4.0% chondroitin sulfate, and the amount of viscoelastic material used was greater in the 2.0% hydroxypropylmethylcellulose group. In addition, the best-corrected visual acuity was significantly better in the hyaluronic acid/ chondroitin sulfate group, but this preferable outcome was only observed at 24 hours after the operation. There were no statistically significant differences between the two ophthalmic viscosurgical devices regarding the central corneal thickness or intraocular pressure measurements at any point in time. The corneal endothelial cell count was significantly higher in the hyaluronic acid/chondroitin sulfate group. CONCLUSION: The ophthalmic viscosurgical device consisting of 1.6% hyaluronic acid/4.0% chondroitin sulfate was more efficient during phacoemulsification and was easier to remove after IOL implantation than 2.0% hydroxypropylmethylcellulose. In addition, the corneal endothelial cell count was significantly higher following the use of hyaluronic acid/chondroitin sulfate than with hydroxypropylmethylcellulose, which promoted an improved level of corneal endothelium protection.

Completion rates of anterior and posterior continuous curvilinear capsulorrhexis in pediatric cataract surgery for surgery performed by trainee surgeons with the use of a low-cost viscoelastic.

Context: Pediatric cataract surgery is traditionally done with the aid of high-molecular-weight viscoelastics which are expensive. It needs to be determined if low-cost substitutes are just as successful. Aims: The study aims to determine the success rates for anterior and posterior capsulorrhexis and intraocular lens (IOL) implantation in the bag for pediatric cataract surgery performed with the aid of a low-molecular-weight viscoelastic. Settings and Design: Nonrandomized observational study. Materials and Methods: Children less than 6 years of age who underwent cataract surgery with IOL implantation in the period May 2008–May 2009 were included. The surgeries were done by pediatric ophthalmology fellows. A standard procedure of anterior capsulorrhexis, lens aspiration with primary posterior capsulorrhexis, anterior vitrectomy, and IOL implantation was followed. Three parameters were studied: successful completion of anterior and posterior capsulorrhexis and IOL implantation in the bag. Results: 33 eyes of 28 children were studied. The success rate for completion was 66.7% and 88.2 % for anterior and posterior capsulorrhexis, respectively. IOL implantation in the bag was successful in 87.9%. Conclusions: 2% hydroxypropylmethylcellulose is a viable low-cost alternative to more expensive options similar to high-molecular-weight viscoelastics. This is of great relevance to hospitals in developing countries.

Dietary Flavonoid Apigenin is not Effective in Preventing Development of a Bleomycin-Induced Murine Model of Scleroderma

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.

[Effects of blanching and hydrocolloid coating of potatoes with methyl cellulose and tragacanth on French-fries oil uptake and qualitative properties]

French fries are a food product with an upward consumptuion trend in Iran. Because of high oil uptake during frying, French fries are an energy-dense food item, providing a very large number of calories to the body. Therefore, efforts to reduce the rate of oil uptake by this popular food item would contribute to the public's health. The purpose of this study was to determine the effects of blanching and coating of potatoes with methyl cellulose and tragacanth on French-fries oil uptake and qualitative properties. Strips of potato [Agria variety] were prepared, blanched in water or a calcium chloride solution [0.5%], coated with a solution of methyl cellulose [0.5, 1.0 and 1.5%], tragacanth [0.5, 1.0 and 1.5%], methyl cellulose [0.5, 1.0 and 1.5%] and sorbitol [0.5%], or tragacanth [0.5, 1.0 and 1.5%] and sorbitol [0.5%] and deep-fried. Oil uptake, moisture content, and color of the French fries were measured and their sensory properties determined and compared with those of control samples. Blanching and hydrocolloid coatings of the samples brought about a decrease in oil uptake and increases in moisture content and texture tenderness of the potato strips [p<0.01]. Blanching in calcium chloride alone reduced oil uptake by 8.61%. In comparison with the control samples, coating with methylcellulose [1.5%] with sorbitol [0.5%] decreased oil uptake from 19.85% to 16.29%. Blanching in calcium chloride resulted in a significant 5%increase in moisture content. The hydrocolloid coatings caused significant increases in moisture content and resistance to cutting of the samples [P<0.01], such that the highest moisture content [44.60%] was obsereved in the samples coated with methyl cellulose [1.5%]. Tragacanth at aconcentartion of 1.5% with sorbitol at a concentartion of 0.5% brought about the highest resistance [211/13 Newton] to cutting. The findings also showed that hydrocolloid coatings resulted in significant incremets in the L [asterisk] b [asterisk], a [asterisk] factors of the French fries color as compared to the control samples. However, there were no significant differences among samples with regard to sensory characteristic

Comparison of the characteristics of several polymer materials used in hydrophilic matrix tablets / 药学学报

Pure and drug hydrophilic matrix tablets were prepared by direct compression method with theophylline as a model drug. The characteristics of four hydrophilic matrix polymers, hydroxypropylmethylcellulose (HPMC), polyethylene oxide (PEO), sodium alginate (NaAlg) and xanthan gum (XG), were compared by investigating the water absorption, swelling, erosion and gel layer strength. The sequence of water absorption rate was XG > NaAlg (H) > PEO > NaAlg (L) > HPMC; The sequence of swelling index was XG > PEO > HPMC > NaAlg; The sequence of erosion rate was NaAlg (L) > NaAlg (H) > PEO80 > PEO200 > PEO300 > XG approximately PEO400 approximately K4M > K15M > PEO600 approximately K100M; The sequence of the gel layer strength was PEO > HPMC > XG > NaAlg. For the PEO and HPMC matrix tablets, with the polymer molecular weight increased, the drug release mechanism was gradually transferred from mainly depending on the erosion to the diffusion; for SAL matrix tablets, the drug release mainly depends on erosion mechanism; and for XG matrix tablets, the drug release mainly depends on non-Fick diffusion mechanism. Comparison of the performance difference between the polymer materials will contribute to rational design and prediction of drug release behaviors from matrix tables and ultimately to achieve clinical needs.