In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization

Context and objective: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery.

Materials and methods: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings.

Results and discussion: There was a big deviation between the T_g of the polymeric caplet from the T_g's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012–0.332?mg/mL and 0.009–0.256?mg/mL for AZT and PSS over 1–28 d.

Conclusion: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.     

Rheological and drug‐release behaviour of a scleroglucan gel matrix at different drug loadings

The aim of this study was to investigate the drug‐loading effects on release and mechanical properties of a scleroglucan gel, with the intention of considering them in delivery systems formulations. The rheological and kinetic properties of a 2 % w/w scleroglucan gel matrix loaded with 0, 0.02, 0.04, 0.06, 0.2 and 0.4 % w/w of theophylline (Th, used as a model drug) were investigated. Rheological measurements were performed in a controlled‐stress rotational‐shear rheometer under isothermal conditions. For theophylline release from the gel a flat Franz cell was used and the kinetic parameters were derived applying a semi‐empirical power law. The influence of scleroglucan molar weight on kinetic and rheological behaviour was also studied. Results suggest two possible effects of drug loading on the gel network: in the 0.04–0.06 % w/w Th range a plasticizing effect and in the 0.2–0.4 % w/w Th range a rigidization effect. In the first range mentioned, the changes in the gel structural properties tested by means of rheological measurements are coincident with changes in drug‐release kinetics. Copyright © 2005 Society of Chemical Industry     

迪银片治疗银屑病临床疗效观察

目的观察迪银片治疗银屑病的临床疗效。方法30例银屑病患者,口服迪银片8周,采用PASI评分法评价治疗前后效果,并观察有无不良反应发生。结果患者痊愈率56.7%,显效率36.7%,总有效率93.3%,无明显的不良反应。结论迪银片是临床治疗银屑病的有效药物之一。     

交联透明质酸的降解及其释药性能

用己二酸二酰肼（ADH）对透明质酸（HA）进行化学修饰，制备交联透明质酸（HA-ADH）薄膜。粘度法测试表明HA-ADH是一种可降解的生物材料，并且与HA相比，HA．ADH的降解速率减慢。在此基础上，研究了以疏水性的替硝唑（TDZ）和亲水性的头孢唑啉钠（CEZ）为模拟药物的HA-ADH药物载体薄膜的释药性能。紫外-可见（UV-Vis）吸收光谱检测表明，HA-ADH是一种疏水性药物TDZ的优良缓释制荆，这是由于TDZ的疏水性和HA-ADH薄膜的缓慢溶胀和降解性能的结合而得到的，药物的释放主要受扩散机制控制。     

Psychosocial treatment of the addictions: General issues facing psychologists.

Treatment of the addictions is changing. Psychosocial treatment programs and research projects have changed the way helping professionals view, treat, and prevent drug abuse. This article reviews the contributions included in this special series; they encompass several general issues facing psychologists who conduct treatment, research, and teaching in the field of addictive behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Use of a YAP1 overexpression cassette conferring specific resistance to cerulenin and cycloheximide as an efficient selectable marker in the yeast Saccharomyces cerevisiae.

Drug-resistance markers for yeast transformation are useful because they can be applied to strains without auxotrophic mutations. However, they are susceptible to technical difficulties, namely lower transformation efficiency and the appearance of drug-resistant mutants without the marker. To avoid these problems, we have constructed a phosphoglycerate kinase (PGK) promoter-driven YAP1 expression cassette, called PGKp-YAP1. Yeast cells containing PGKp-YAP1 were resistant to cycloheximide, a protein synthesis inhibitor, and also to cerulenin, a fatty acid synthesis inhibitor, but not to other drugs tested. The transformation efficiency of PGKp-YAP1 using cerulenin selection was comparable to that using a URA3 auxotrophic marker when low concentrations of cerulenin were used. Non-transformed drug-resistant colonies did appear on the low-concentration cerulenin plates. However, these non-transformed colonies could easily be identified, based on their cycloheximide sensitivity and/or their resistance to aureobasidin A to which the transformants were sensitive. Therefore, the dual drug resistance of PGKp-YAP1 could be used as an effective selection for PGKp-YAP1 recipient cells. The PGKp-YAP1 marker was used to disrupt the LYS2 gene and to transform an industrial yeast strain, indicating that this marker can be used for efficient and reliable gene manipulations in any Saccharomyces cerevisiae strain.     

UV法测定聚甲基丙烯酸酯纳米粒中胰岛素的包封率

建立一种简便易行的测定聚甲基丙烯酸酯胰岛素纳米粒中游离胰岛素含量方法.用Nanosep OD100C33超滤膜分离纳米粒和游离药物,在276 nm处测定药物的吸光度,建立胰岛素含量测定方法,并对线性、回收率、精密度等指标进行考察,最后测定各种胰岛素和载体比例混合的纳米粒的包封率.结果发现,该超滤膜能较好地分离纳米粒和游离的药物,在0.11～1.10 u/mL范围内,药物在276 nm的吸光度和浓度存在良好的线性关系(r=0.999 8),线性方程为A=0.868 8C-0.001 6,高、中、低3种浓度的回收率和精密度良好.该方法操作简单、结果可靠,可用于胰岛素纳米粒中药物包封率的测定.     

A Tale of Two Cities: Financing Two Voucher Programs for Substance Abusers Through Community Donations.

Voucher-based reinforcement therapy (VBRT) is an effective drug abuse treatment, but the cost of VBRT rewards has limited its dissemination. Obtaining VBRT incentives through donations may be one way to overcome this barrier. Two direct mail campaigns solicited donations for use in VBRT for pregnant, postpartum, and parenting drug users in Toronto, Ontario, Canada, and in Los Angeles, California. In Toronto, 19% of those contacted over 2 months donated $8,000 ($4,000/month) of goods and services. In Los Angeles, nearly 26% of those contacted over 34 months donated $161,000 ($4,472/month) of goods and services. Maintaining voucher programs by soliciting donations is feasible and sustainable. The methods in this article can serve as a guide for successful donation solicitation campaigns. Donations offer an alternative for obtaining VBRT rewards for substance abuse treatment and may increase its dissemination. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Review of Qualité de vie et drogues. Place aux jeunes.

Reviews the book, Qualité de vie et drogues. Place aux jeunes (1986). In this volume, the author shares his initiatives in the plan of therapeutic and preventive intervention. This book discusses drug use and quality of life in young people. (PsycINFO Database Record (c) 2010 APA, all rights reserved)