Formulation,optimization and evaluation of transferosomal gel for transdermal insulin delivery

The present study deals with the development of transferosomal gel containing insulin by reverse phase evaporation method for painless insulin delivery for use in the treatment of insulin dependent diabetes mellitus. The effect of independent process variables like ratio of lipids (soya lecithin:cholesterol), ratio of lipids and surfactants, and ratio of surfactants (Tween 80:sodium deoxycholate) on the in vitro permeation flux (μg/cm²/h) of formulated transferosomal gels containing insulin through porcine ear skin was optimized using 2³ factorial design. The optimal permeation flux was achieved as 13.50 ± 0.22 μg/cm²/h with drug entrapment efficiency of 56.55 ± 0.37% and average vesicle diameter range, 625–815 nm. The in vitro insulin permeation through porcine ear skin from these transferosomal gel followed zero-order kinetics (R² = 0.9232–0.9989) over a period of 24 h with case-II transport mechanism. The in vitro skin permeation of insulin from optimized transferosomal gel by iontophoretic influence (with 0.5 mA/cm² current supply) also provided further enhancement of permeation flux to 17.60 ± 0.03 μg/cm²/h. The in vivo study of optimized transferosomal gel in alloxan-induced diabetic rat has demonstrated prolonged hypoglycemic effect in diabetic rats over 24 h after transdermal administration.     

透皮给药新进展

经皮治疗系统 (ｔｒａｎｓｄｅｒｍａｌｔｈｅｒａｐｅｕｔｉｃｓｙｓｔｅｍ ,ＴＴＳ)或称经皮给药系统 (ｔｒａｎｓｄｅｒｍａｌｄｒｕｇｄｅｌｉｖｅｒｙｓｙｓｔｅｍ ,ＴＤＤＳ) ,是药物通过皮肤吸收的一种方法 ,它可避免肝脏首过效应 ,较长时间维持恒定速率给药及有效血药浓度。药物透皮吸收的主要屏障是角质层 (由约 4 0 %的蛋白质、4 0 %的水、15 %～ 2 0 %的类脂组成 ) ,其中类脂与蛋白质水凝胶组成网状结构。药物的透皮吸收过程就是药物在类脂相与水相间的分配、扩散、吸附和解吸附过程[1] 。但很多药物透皮吸收很难达到临床治疗所…     

微乳在经皮给药系统中的应用

微乳经皮给药是目前国内外药学工作者研究的重点,也是目前药物制剂研发热点之一。本文主要从微乳的组成、促渗机制、微乳在经皮给药中的应用3个方面进行了综述。微乳经皮给药具有很好的应用前景。     

Synthesis of 6- and 9-Ethylocatadecanoic Acids

Specific branched fatty acids are of great interest in the search of a new type of drug penetration enhancers across human skin for transdermal drug delivery and in gaining an understanding of structure-activity relationships with skin lipids. A convenient synthesis has therefore been developed especially for ethyloctadecanoic acids. The successful syntheses of 6- and 9-ethyloctadecanoic acids are reported here.     

透皮吸收促进剂在经皮给药系统中的质控和评价方法

透皮吸收制剂是国际上第三代药物制剂的研究重点领域。透皮吸收促进剂在处方中的合理应用和质量控制及其评价方法日益重要。通过对透皮促进机理、协同作用等的探讨,介绍透皮吸收促进剂的选用原则,并对透皮给药制剂和局部用药局部起效的皮肤外用制剂处方中使用的要求加以讨论,介绍了现有的评价方法和基本的技术要求。     

Transdermal delivery of β-blockers

β-Adrenoceptor blocking drugs (β-blockers) are one of the most frequently used class of cardiovascular drugs that are mainly used in conventional dosage forms., which have their own limitations including hepatic first-pass metabolism, high incidence of adverse effects due to variable absorption profiles, higher frequency of administration and poor patient compliance. Essentially, attempts have been made to develop novel drug delivery systems for β-blockers, including transdermal delivery systems, to circumvent the drawbacks of conventional drug delivery. However, so far none of the β-blocker drugs have been marketed as transdermal delivery systems. Nevertheless, there have been noteworthy research endeavours worldwide at the laboratory level to investigate the skin permeation and to develop transdermal formulations of β-blockers including: propranolol, metoprolol, atenolol, timolol, levobunolol, bupranolol, bopindolol, mepindolol, sotalol, labetolol, pindolol, acebutolol and oxprenolol. Innovative research exploiting penetration-enhancing strategies, such as iontophoresis, electroporation, microneedles and sonophoresis, holds promise for the successful use of these drugs as consumer-friendly transdermal dosage forms in clinical practice. This paper presents an overview of the transdermal research on this important class of drugs.     

Transdermal delivery of triptolide–phospholipid complex to treat rheumatoid arthritis

The aim of this study was to develop and evaluate a triptolide phospholipid complex (TPCX) for the treatment of rheumatoid arthritis (RA) by transdermal delivery. TPCX was prepared and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) analysis, transmission electron microscope (TEM), and scanning electron microscope (SEM). The solubility of TPCX was determined. Then, a TPCX cream was prepared to evaluate its percutaneous permeability and the antiarthritis effect. The transdermal permeability was determined using the Franz method, and a microdialysis system was used for skin pharmacokinetic study. A rat model of RA was prepared to evaluate the pharmacological effects. TPCX increased the solubility of triptolide in water, and the percutaneous permeability of TPCX cream was greatly enhanced compared with triptolide cream. The skin pharmacokinetic study indicated that TPCX cream has a longer biological half-life (t_1/2) and mean residence time (MRT), but it has a shorter T_max than that of triptolide cream in vivo. The area under the curve (AUC_0–t)/AUC_0–∞) and the peak concentration (C_max) of TPCX cream were obviously higher than those of triptolide cream. The TPCX-loaded cream alleviated paw swelling and slowed down the progression of arthritis by inhibiting the inflammatory response by down regulating the TNF-α, IL-1β, and IL-6 levels, thus exhibiting excellent antiarthritic effects. In summary, the prepared TPCX effectively increases the hydrophilicity of triptolide, which is good for its percutaneous absorption and enhances its effect on RA rats. TPCX can be a good candidate for the transdermal delivery to treat RA.     

A natural lipopeptide of surfactin for oral delivery of insulin

Abstract

Surfactin, a natural lipopeptide produced by Bacillus, is gaining attention for potentially biomedical and pharmaceutical applications. Here, surfactin was assayed for oral delivery of insulin (INS) by its ability to bind to and promote protein to penetrate through the cell membrane. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, surfactin was found to form co-precipitates with INS to protect it from acidic and enzymatic attack in the gastrointestinal tract. Further analysis by non-reductive electrophoresis showed surfactin could bind to INS forming heteropolymers. Analysis with circular dichroism, we found this binding significantly influenced the INS structure with decreased rigid α-helix and β-turn, but with increased flexible β-sheet and random coil. The change with more flexible structure was favorable for INS to penetrate through the cell membrane. Fluorescence spectra analysis also showed surfactin could lead Phe and Tyr in the inner of INS exposed outside, further promoting INS permeabilization by improving the hydrophobic-lipophilic interactions between INS and cell membrane. As a result, the effective permeability (Peff) of INS plus surfactin was 4.3 times of that of INS alone. In vivo assay showed oral INS with surfactin displayed excellent hypoglycemic effects with a relative bioavailability of 12.48% and 5.97% in diabetic mice and non-diabetic dogs, respectively. Summary, surfactin is potential for oral delivery of INS by its role as an effective protease inhibitor and permeability enhancer.     

Spray-on transdermal drug delivery systems

Introduction: Transdermal drug delivery possesses superior advantages over other routes of administration, particularly minimizing first-pass metabolism. Transdermal drug delivery is challenged by the barrier nature of skin. Numerous technologies have been developed to overcome the relatively low skin permeability, including spray-on transdermal systems.

Areas covered: A transdermal spray-on system (TSS) usually consists of a solution containing the drug, a volatile solvent and in many cases a chemical penetration enhancer. TSS promotes drug delivery via the complex interplay between solvent evaporation and drug–solvent drag into skin. The volatile solvent carries the drug into the upper layers of the stratum corneum, and as the volatile solvent evaporates, an increase in the thermodynamic activity of the drug occurs resulting in an increased drug loading in skin.

Expert opinion: TSS is easily applied, delivering flexible drug dosage and associated with lower incidence of skin irritation. TSS provides a fast-drying product where the volatile solvent enables uniform drug distribution with minimal vehicle deposition on skin. TSS ensures precise dose administration that is aesthetically appealing and eliminates concerns of residual drug associated with transdermal patches. Furthermore, it provides a better alternative to traditional transdermal products due to ease of product development and manufacturing.     

不锈钢微针经皮给药的研究

目的：将不锈钢微针阵列应用于经皮给药。考察离体大鼠皮肤经不同针形微针预处理相同时间、相同针形微针预处理不同时间后，模型药物鬼臼毒素经大鼠皮肤的透皮能力。方法：微针预处理大鼠皮肤后，用改进的Franz扩散池研究鬼臼毒素对皮肤的透皮速率。高效液相色谱法测定鬼臼毒素的含量。结果：皮肤经微针预处理后进行鬼臼毒素透皮，其透皮速率比未经微针处理时有明显提高。三角形微针、梯形微针、矛形微针对鬼臼毒素的促渗能力依次增强；三者所引起的鬼臼毒素在皮肤中的滞留量有显著差异。同种针形微针预处理皮肤时间越长，鬼臼毒素的透皮速率越大；但微针预处理时间对皮肤中的药物滞留量无显著影响。结论：微针用于药物经皮给药时，微针针形、微针的预处理时间对药物的经皮渗透具有重要影响。     

多肽及蛋白质类药物智能化原位凝胶控释给药系统研究进展

本文综述了国内外近年来多肽及蛋白质类药物智能化原位凝胶控释给药系统的研究进展,主要包括温敏型、pH敏感型、电场驱动型及复合型智能化原位凝胶控释新剂型、新技术研究进展。     

Formulation and characterization of an oily-based system for oral delivery of insulin

The present work explored the possibility of formulating an oral insulin delivery system by combining the advantages of nanoencapsulation and the use of oily vehicle. The parameters affecting formulation such as association efficiency were characterized. The preparation was evaluated for its chemical, physical and biological stability. The preparation has unimodal particle size distribution with a mean diameter of 108 ± 9 nm. Insulin was protected from gastric enzymes by incorporation into lipid-based formulation. The results of RP HPLC and ELISA indicated that insulin was able to withstand the preparation procedure. Insulin in the preparations was stable for a period of one month at storage temperatures of 4 and 25 °C. It was also biologically active and stable as demonstrated by the remarkable reduction of blood glucose levels of the STZ-diabetic rats after oral administration of the preparation. Moreover, hypoglycemic effect of nanoparticles administered orally was sustained for a longer period of time compared to the subcutaneous injection. These results clearly evidenced the ability of the nanoparticles to enhance the pharmacological response of insulin when given orally and could be used to deliver other peptides.     

Glucose-sensitive gel rheology of dextran-concanavalin A mixtures suitable for self-regulating insulin delivery

Aqueous concentrated plain mixtures of dextran and concanavalin A (con A) were examined for their rheological response to glucose for comparison with previously studied partially photopolymerized acrylic derivatives. Non-destructive oscillatory tests were undertaken within the linear viscoelastic range to examine the relationship between the rheometry and the stoichiometry of the interactive materials and to examine rheological parameters as affected by molecular weight, component ratio, temperature and glucose concentrations between 0 and 1% w/w. These simple formulations were studied at 1 and 10 Hz at 0.5% strain at both 20 and 37°C. A second simplified rheological test was undertaken to demonstrate gel-sol reversibility and to produce a measure of equilibria created between these gels and glucose solutions with which they are in contact. This mimics the conditions in which the gel acts as a responsive gateway in the insulin delivery device. It proved that the gels equilibrate with glucose solutions, rather than indiscriminately removing glucose. This is important in terms of producing a delivery device that can respond in a reversible, glucose concentration-dependent manner. The method used for this is capable of relative values only but provides information not obtainable from conventional rheometry.     

Biomaterials as novel penetration enhancers for transdermal and dermal drug delivery systems

Abstract

The highly organized structure of the stratum corneum provides an effective barrier to the drug delivery into or across the skin. To overcome this barrier function, penetration enhancers are always used in the transdermal and dermal drug delivery systems. However, the conventional chemical enhancers are often limited by their inability to delivery large and hydrophilic molecules, and few to date have been routinely incorporated into the transdermal formulations due to their incompatibility and local irritation issues. Therefore, there has been a search for the compounds that exhibit broad enhancing activity for more drugs without producing much irritation. More recently, the use of biomaterials has emerged as a novel method to increase the skin permeability. In this paper, we present an overview of the investigations on the feasibility and application of biomaterials as penetration enhancers for transdermal or dermal drug delivery systems.     

皮肤给药的经皮吸收与测量技术研究进展

经皮给药系统（TDDS）可避免首关效应、胃肠道破坏，为新型皮肤给药系统，可通过控制释放而延长治疗效果，成为药物制剂开发研究的热点之一。但是，药物的理化性质以及皮肤屏障影响药物的经皮吸收。综述了TDDS常用的促渗透技术，包括化学、物理、纳米、天然促渗透技术；介绍了促渗透能力的测定方法，包括体外、离体和体内评估皮肤渗透性的方法。通过对经皮药物递送系统和经皮吸收能力测定方法的归纳与总结，以期为TDDS的合理使用和快速发展提供参考。     

胰岛素智能给药系统的研究

本文简要概述了近几年胰岛素智能给药系统的研究进展,为胰岛素非注射给药途径的研究提供参考。     

乙醇脂质体透皮作用的研究与发展

目的：介绍乙醇脂质体透皮作用的研究与发展。方法：综合分析乙醇脂质体的组成及一般特性、制备及乙醇脂质体载药系统透皮给药的药剂学促透机制、最新的基础实验和研究进展。结果：作为各种药物的载体，乙醇脂质体具有其良好的药物包裹率和显著的促进药物透皮吸收特性。结论：乙醇脂质体新剂型透皮给药具有广阔的应用前景。     

Controlled release systems for insulin delivery

Diabetes mellitus is a major cause of mortality in industrialised countries, and insulin has remained indispensable in the treatment of diabetes mellitus since its discovery. Generally, patients with diabetes mellitus need a relatively constant basal insulin supply to mimic a near-normal physiological pattern of insulin secretion. However, as a consequence of very short in vivo half-lifes, poor oral bioavailability and current lack of alternative delivery routes, insulin requires single or multiple daily subcutaneous injections to achieve the desired therapeutic effect, which is inconvenient and painful and with poor patient compliance. Therefore, there is a need for insulin delivery systems that have the capability of releasing the loaded insulin at a controlled and sustained rate for a prolonged period. This review examines recent (2000 – 2004) patents on the controlled release systems for insulin delivery, including those for injectable, oral, pulmonary and transdermal delivery, and the glucose-responsive controlled-release systems.     

经皮给药的研究进展

药物的透皮给药主要受到皮肤障碍、药物的分子量和亲水/油性等因素的影响.利用物理和化学方法,同时,辅以载体方法可有效提高药物(尤其是生物大分子药物和复方中药)经皮给药效率.随着透皮给药的不断发展改进,经皮给药系统一定会发挥更大的潜力.