Advanced delivery of Ciclosporin A: present state and perspective

Ciclosporin A has been used as an immunosuppressor for organ transplantation and other autoimmune disorders for a number of years. Its poor biopharmaceutical characteristics of low solubility and permeability makes the uphill task of designing delivery systems even more challenging for the drug delivery scientist. Works have been performed to investigate administration through various body routes, and have employed approaches that use as emulsions, microspheres, nanoparticles, liposomes, physical and chemical penetration enhancers. Although progress has been made, there is still room for improvement in the application of ciclosporin A, as none of these formulations is ideal.     

Patent focus on drug delivery: June - November 1999

The article highlights the most recent disclosures in the field of drug formulation and delivery for the period June - November 1999. The limited number of patents published in this period in the field of drug delivery focus on the delivery of the newer biopharmaceuticals such as genes and vaccines. In addition patents on novel vectors for drug delivery are highlighted - these concentrate on biological-based systems rather than polymeric systems which have been of particular interest over recent years.     

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.     

On the Suitability of Porcine Labial Mucosa as a Model for Buccal Mucosal Drug Delivery Research

Contrary to human, porcine mucosa of the inner side of the lip is parakeratinized. Thus, although desirable due to its large surface area, it does not closely resemble human buccal mucosa to be considered a suitable model for systemic drug delivery research. Nevertheless, it can be utilized for comparative screening of topical or systemic delivery of bioactive agents, mostly lipophilic such as cannabinoids.     

泊洛沙姆407在制剂中的应用进展

泊洛沙姆407是医药领域应用非常广泛的一种辅料.本文主要介绍了泊洛沙姆407的理化性质,总结了其在眼部给药、经皮给药、直肠给药、阴道给药、注射给药中的应用情况、存在的问题和发展前景.     

Biomaterials-based nanofiber scaffold: targeted and controlled carrier for cell and drug delivery

Nanofiber scaffold formulations (diameter less than 1000?nm) were successfully used to deliver the drug/cell/gene into the body organs through different routes for an effective treatment of various diseases. Various fabrication methods like drawing, template synthesis, fiber-mesh, phase separation, fiber-bonding, self-assembly, melt-blown, and electrospinning are successfully used for fabrication of nanofibers. These formulations are widely used in various fields such as tissue engineering, drug delivery, cosmetics, as filter media, protective clothing, wound dressing, homeostatic, sensor devices, etc. The present review gives a detailed account on the need of the nanofiber scaffold formulation development along with the biomaterials and techniques implemented for fabrication of the same against innumerable diseases. At present, there is a huge extent of research being performed worldwide on all aspects of biomolecules delivery. The unique characteristics of nanofibers such as higher loading efficiency, superior mechanical performance (stiffness and tensile strength), controlled release behavior, and excellent stability helps in the delivery of plasmid DNA, large protein drugs, genetic materials, and autologous stem-cell to the target site in the future.     

鼻脑递送给药装置技术要点探讨及监管考量

针对越来越迫切的脑部疾病治疗需求,鼻脑递送技术利用鼻腔与脑组织间特殊的生理连接,避开血脑屏障、肝脏首过效应等生理因素,采用非侵入性给药方式将治疗脑部疾病的药物直接递送入脑,发挥治疗作用,为解决日益严重的脑部疾病问题提供了新的可能。本文在分析鼻脑递送生理特点和优势的基础上,重点梳理了近年来鼻脑递送给药装置方面的最新研究进展,探讨此类特殊装置的技术关键点,并结合国内外研发及产业现状提出监管考量,以期为鼻脑递送技术的深入发展和更为广阔的应用提供建议。     

脉冲释药系统的新进展

综述近年来脉冲释药系统的新进展。脉冲释药系统是一种按照生理节律设计、定时定量脉冲式释放有效治疗量药物的剂型。根据剂型设计原理和药物释药机制,将脉冲释药系统分为预设药物传递系统、闭环反馈型传递系统和开环传递系统三大类。     

Archaeosomes: an excellent carrier for drug and cell delivery

Archaeosomes as liposomes made with one or more ether lipids that are unique to the domain of Archaeobacteria, found in Archaea constitute a novel family of liposome. Achaean-type lipids consist of archaeol (diether) and/or caldarchaeol (tetraether) core structures. Archaeosomes can be produced using standard procedures (hydrated film submitted to sonication, extrusion and detergent dialysis) at any temperature in the physiological range or lower, therefore making it possible to encapsulate thermally stable compounds. Various physiological as well as environmental factors affect its stability. Archaeosomes are widely used as drug delivery systems for cancer vaccines, Chagas disease, proteins and peptides, gene delivery, antigen delivery and delivery of natural antioxidant compounds. In this review article, our major aim was to explore the applications of this new carrier system in pharmaceutical field.     

Advances in ocular drug delivery: emphasis on the posterior segment

Introduction: Recent advances in pharmacological therapies to treat ocular diseases such as glaucoma, age-related macular degeneration, diabetic macular edema and retinal vascular occlusions have greatly improved the prognosis for these diseases. Due to these advances in pharmacological therapy, there is a great deal of interest in minimally invasive delivery methods, which has generated rapid developments in the field of ocular drug delivery.

Areas covered: This review will summarize currently available and recent developments for ocular drug delivery to both the anterior and posterior segments. Modes of delivery, including topical, systemic, transcleral/periocular and intravitreal, will be discussed and corresponding examples will be given. This review will highlight the advantages and disadvantages of each mode of delivery and discuss strategies to address these issues.

Expert opinion: An ideal therapy should maintain effective levels of drug for the intended duration of treatment following a single application, yet a significant number of months of therapy may be required. There are numerous approaches under investigation to improve treatment options. From the use of novel biomaterial implants and depots for sustained release, to prodrug formations, to iontophoresis to improve drug delivery, the main emphasis will continue to be placed on less invasive, longer acting, sustained release formulations in the treatment of numerous ocular disorders.     

Drug Delivery by Phonophoresis

Phonophoresis is defined as the migration of drug molecules, contained in a contact agent, through the skin under the influence of ultrasound. Several drugs have been introduced into the body by this technique. The design of a phonophoretic drug delivery system is in developmental stages in various research laboratories. Parameters affecting the delivery of drugs by this technique and devices available for drug delivery purposes are discussed in this review.     

Cell-penetrating peptides for the delivery of nucleic acids

Introduction: Different gene therapy approaches have gained extensive interest lately and, after many initial hurdles, several promising approaches have reached to the clinics. Successful implementation of gene therapy is heavily relying on finding efficient measures to deliver genetic material to cells. Recently, non-viral delivery of nucleic acids and their analogs has gained significant interest. Among non-viral vectors, cell-penetrating peptides (CPPs) have been extensively used for the delivery of nucleic acids both in vitro and in vivo.

Areas covered: In this review we will discuss recent advances of CPP-mediated delivery of nucleic acid-based cargo, concentrating on the delivery of plasmid DNA, splice-correcting ONs, and small-interfering RNAs.

Expert opinion: CPPs have proved their potential as carriers for nucleic acids. However, similarly to other non-viral vectors, CPPs require further development, as efficient systemic delivery is still seldom achieved. To achieve this, CPPs should be modified with entities that would allow better endosomal escape, targeting of specific tissues and cells, and shielding agents that increase the half-life of the vehicles. Finally, to understand the clinical potential of CPPs, they require more thorough investigations in clinically relevant disease models and in pre-clinical and clinical studies.     

导乐陪伴分娩对初产妇第二产程的影响

目的探讨导乐陪伴分娩对初产妇第二产程的影响。方法随机选择506例导乐分娩产妇作为观察组,512例非导乐分娩产妇作为对照组,比较两组产妇的第二产程时间、因宫缩乏力应用缩宫素的比例、产后出血比例和新生儿窒息比例。结果观察组第二产程时间、因宫缩乏力应用缩宫素比例、产后出血比例和新生儿窒息比例分别为(57±21)min、10.2%、0.62%和1.1%,对照组分别为(63±26)min、35.7%、0.74%和2.5%,观察组第二产程时间较短、因宫缩乏力应用缩宫素比例、产后出血比例和新生儿窒息比例均较低,差异具有显著性意义(P<0.05)。结论导乐分娩促进产程进展,缩短第二产程时间、减少宫缩乏力、产后出血率和新生儿窒息的发生,提高产科质量,是一种值得推广的方法。     

口服结肠定位给药系统

综述了近年来口服结肠定位给药系统的发展状况 ,并评价了各类结肠定位给药系统的优、缺点和发展前景     

Nanoemulsions as potential vehicles for transdermal and dermal delivery of hydrophobic compounds: an overview

Introduction: In recent years, nanoemulsions have been investigated as potential drug delivery vehicles for transdermal and dermal delivery of many compounds especially hydrophobic compounds in order to avoid clinical adverse effects associated with oral delivery of the same compounds. Droplet size and surface properties of nanoemulsions play an important role in the biological behavior of the formulation.

Areas covered: In this review, current literature of transdermal and dermal delivery of hydrophobic compounds both in vitro as well as in vivo has been summarized and analyzed.

Expert opinion: Nanoemulsions have been formulated using a variety of pharmaceutically acceptable excipients. In many cases of dermal and transdermal nanoemulsions, the skin irritation or skin toxicity issues on human beings have not been considered which needs to be evaluated properly. In the last decade, much attention has been made in exploring new types of nanoemulsion-based drug delivery system for dermal and transdermal delivery of many hydrophobic compounds. This area of research would be very advantageous for formulation scientists in order to develop some nanoemulsion-based formulations for their commercial exploitation and clinical applications.     

Carbon nanotubes part II: a remarkable carrier for drug and gene delivery

Introduction: Carbon nanotubes (CNT) have recently been studied as novel and versatile drug and gene delivery vehicles. When CNT are suitably functionalized, they can interact with various cell types and are taken up by endocytosis.

Areas covered: Anti-cancer drugs cisplatin and doxorubicin have been delivered by CNT, as well as methotrexate, taxol and gemcitabine. The delivery of the antifungal compound amphotericin B and the oral administration of erythropoietin have both been assisted using CNT. Frequently, targeting moieties such as folic acid, epidermal growth factor or various antibodies are attached to the CNT-drug nanovehicle. Different kinds of functionalization (e.g., polycations) have been used to allow CNT to act as gene delivery vectors. Plasmid DNA, small interfering RNA and micro-RNA have all been delivered by CNT vehicles. Significant concerns are raised about the nanotoxicology of the CNT and their potentially damaging effects on the environment.

Expert opinion: CNT-mediated drug delivery has been studied for over a decade, and both in vitro and in vivo studies have been reported. The future success of CNTs as vectors in vivo and in clinical application will depend on achievement of efficacious therapy with minimal adverse effects and avoidance of possible toxic and environmentally damaging effects.     

“Programmed Polymeric Devices” for Pulsed Drug Delivery

Pharmaceutical research strives to design drug delivery systems that respond to therapeutic needs. Considering the facts that physiologic parameters (e.g., heart rate, blood pressure, and plasma concentration of hormones, plasma proteins, and enzymes) display constancy over time, drug delivery systems with a constant release profile have been designed. However, because of circadian rhythms in physiologic parameters and pathologic conditions (e.g., asthma, angina pectoris), the conventional paradigm concerning drug concentrations "the flatter the better" may not be what the organism may need. Instead, to correlate with our biological needs, "precisely timed drug delivery," which could be accomplished with "programmable dosage forms," is required. Precisely timed drug delivery may maximize therapeutic efficacy, may minimize dose frequency, and may reduce toxicity by avoiding side effects and drug tolerance. This paper outlines the concepts that have been proposed to release drugs in a pulsed manner from pharmaceutical devices.     

Recent advances in polymeric materials for the delivery of RNA therapeutics

ABSTRACT

Introduction: The delivery of nucleic acid therapeutics through non-viral carriers face multiple biological barriers that reduce their therapeutic efficiency. Despite great progress, there remains a significant technological gap that continues to limit clinical translation of these nanocarriers. A number of polymeric materials are being exploited to efficiently deliver nucleic acids and achieve therapeutic effects.

Areas covered: We discuss the recent advances in the polymeric materials for the delivery of nucleic acid therapeutics. We examine the use of common polymer architectures and highlight the challenges that exist for their development from bench side to clinic. We also provide an overview of the most notable improvements made to circumvent such challenges, including structural modification and stimuli-responsive approaches, for safe and effective nucleic acid delivery.

Expert opinion: It has become apparent that a universal carrier that follows ‘one-size’ fits all model cannot be expected for delivery of all nucleic acid therapeutics. Carriers need to be designed to exhibit sensitivity and specificity toward individual targets diseases/indications, and relevant subcellular compartments, each of which possess their own unique challenges. The ability to devise synthetic methods that control the molecular architecture enables the future development that allow for the construction of ‘intelligent’ designs.     

不同分娩方式对母婴健康状况的影响

目的探讨不同分娩方式对母婴健康状的影响。方法采用前瞻性的研究方法,追踪随访我院2007年3月至2009年3月期间顺产和剖宫产的孕产妇以及新生儿在产时和产后的健康状况。结果顺产组的孕产妇在产后的抑郁倾向以及并发症的发生概率明显低于剖宫产组,P〈0．05;并且顺产组的新生儿胆红素指数和Apgar评分≤7分的发生率也低于剖宫产组,P〈0．05。结论剖宫产对母婴健康状况的影响比顺产更加明显,医生和孕产妇应谨慎选择分娩方式,以减少不必要的影响。     

产钳在瘢痕子宫经阴道分娩中的应用

目的分析瘢痕子宫孕妇经阴道试产中宫口开全后迅速、安全娩出胎儿的临床手段,确定产钳助娩在瘢痕子宫经阴道分娩中的临床应用价值。方法分析瘢痕子宫再次足月妊娠宫口开全后因第二产程停滞行手术产44例,根据手术方式分为2组,组1为产钳助娩20例,组2为剖宫产24例。比较2组新生儿娩出时间,新生儿窒息,新生儿产伤,产后出血的发生,软产道裂伤(Ⅲ°、Ⅳ°),先兆子宫破裂的发生率。结果瘢痕子宫再次足月妊娠经阴道分娩应用产钳可有效缩短胎儿娩出时间,减少产后出血的发生;不增加先兆子宫破裂、新生儿窒息、产伤、软产道裂伤的机率。能安全有效地辅助胎头娩出,有效降低剖宫产率。结论合理的产钳应用在瘢痕子宫经阴道分娩中是安全有效的,且能降低剖宫产率。