应用芬太尼透皮贴剂减轻中度癌痛

目的观察芬太尼透皮贴剂治疗中度癌痛病人的效果,为恰当选择使用芬太尼透皮贴剂的时机提供临床依据。方法2003年3月~12月在哈尔滨医科大学附属肿瘤医院宁养院接受宁养服务的中度癌痛患者108例,单中心开放试验给药,自身对照方法进行研究,观察周期28天。结果符合入组标准患者108例,其中完成15天连续用药患者98例,治疗前疼痛评分平均为5.2173±0.3185,第15天为0.9184±0.7822,其中79.6%的患者达到基本无痛,其他患者仅有轻度疼痛,从平均用药剂量及疼痛评分变化曲线图可以发现,疼痛强度很快下降,而平均药物剂量增长缓慢,尽早给癌痛患者进行规范化的疼痛处理,相对较低的剂量即可取得良好镇痛效果。结论芬太尼透皮贴剂可以安全用于中度癌痛的治疗。我们认为最佳使用时机为常规一、二阶梯镇痛药物效果不满意,疼痛评分在4~6分以上即可使用,尽早减轻疼痛,提高患者的生活质量。     

微针用于生物大分子及纳米药物透皮给药的尝试与挑战

生物大分子及纳米药物,比如,亚单位疫苗、DNA疫苗、以及针对真皮层的治疗药物,作为近年来新兴的治疗药物,在有些治疗领域有着透皮给药的需求。由于具有靶向性高,疗效显著等特点,生物大分子及纳米药物逐渐成为新的研究热点。微针作为一种新型的给药技术,不仅具有无痛、给药方便等优点,而且运用物理手段可大幅提高大分子甚至纳米药物的透皮吸收及皮层靶向,能够避过胃肠道消化作用以及肝脏首过效用。将微针技术与生物大分子药物相结合,能够同时发挥两者的优势,实现高靶向生物药物的无痛给药。本文简述微针透皮给药技术、以及生物大分子给药的研究进展,对微针技术用于生物大分子及纳米药物透皮给药的尝试研究做了介绍和总结,对存在的技术挑战进行了分析和展望。     

中药透皮吸收对急性呼吸道感染的防治作用

目的应用中药黄连解毒汤加味透皮吸收剂对儿童急性呼吸道感染及治疗中的肿瘤患者进行临床观察。方法将黄连解毒汤加味制成透皮吸收剂,外敷于颌下部,可减去患者服药的痛苦,又利于持久发挥药效。结果与结论单独给药可治疗儿童上呼吸道感染;抗生素伍用透皮吸收剂与单独使用抗生素比,可缩短治愈时间,见效快;对肿瘤患者可有效预防继发性感染。     

微针技术在透皮给药方向的研究进展

微针作为一种透皮给药技术,具有给药准确、快速、高效、操作简便、无痛等优点,十几年来发展迅速,随着研究的深入其应用范围逐渐扩大,目前微针可用于小分子、生物制剂、疫苗、细胞内DNA/RNA等透皮递送。疫苗、糖尿病、皮肤病是微针研究的主要方向,在此主要介绍微针在这3个领域的临床试验成果及最新研究进展。     

中药透皮吸收促进剂的研究进展

经皮给药系统(transdermal drug delivery system,TDDS)由于具有超越一般给药方式的独特优点,其研究已经成为第3代药物制剂开发研究的中心内容之一。然而在经皮给药的临床应用中,人们发现,药物的经皮吸收存在着各种障碍,使得药物很难达到预期的有效的治疗效果。近年来,透皮吸收促进剂(penetration enhancers,PE)的应用为经皮给药系统的研究与应用带来了契机,而天然的中药PE以其具有起效快、效果好、副作用小等优点,正日益引起人们的重视,显示出广阔的发展前景。     

助剂对高效氯氰菊酯在粘虫表皮渗透性的影响

研究了3类助剂(矿物油、高级脂肪酸、非离子表面活性剂)、两种给药方式(点滴法、浸渍法)对非内吸性杀虫剂高效氯氰菊酯在粘虫Mythimna separata表皮渗透性的影响。证明对适宜的助剂和给药方式而言,该渗透性在一定范围内与药剂中助剂含量和给药后的时间成正相关。助剂的一些组合对渗透性具有一定的协同作用。     

芦荟多糖含量测定及芦荟膏体外透皮吸收的实验研究

目的:研究芦荟膏中各功能成分体外透皮吸收的能力。方法:以Wistar大鼠的背部皮肤为透皮实验原料,每隔一定时间通过分光光度法和高效液相色谱法测定透皮后接收池内芦荟多糖及蒽醌类含量。结果:随着芦荟膏剂量的增加,渗透量逐渐增加,芦荟膏中芦荟多糖、芦荟大黄素、芦荟苷的渗透量随时间延长逐渐增加,但是渗透速率逐渐降低。结论:芦荟膏有较强的体外透皮吸收能力,芦荟膏经皮给药能充分发挥其作用。     

丁丙诺啡透皮贴剂控制肩周炎患者疼痛的效果观察

目的:探讨丁丙诺啡透皮贴剂治疗肩关节周围炎的患者对于疼痛的缓解效果和肩关节活动功能的改善作用。方法:搜集本院近5年来门诊就诊及住院治疗的肩周炎患者152例,全部患者均规范化按照VAS评分使用镇痛药物。其中,78例患者在达到中度及以上疼痛水平时,额外加用丁丙诺啡透皮贴剂。每隔3月通过电话随访量化患者疼痛评分变化情况,门诊随访检查患者肩关节活动功能,并使用Constant-Murley肩关节功能评分量表进行数字化评估。结果:152例肩周炎患者在治疗观察期间,疼痛及肩关节活动功能均有一定程度的缓解和改善,在观察期末,平均Constant-Murley肩关节功能评分保持于80分水平。在治疗观察期内,外用丁丙诺啡透皮贴的患者在6-18月期间时,Constant-Murley肩关节功能评分上升速度明显高于对照组(P0.05)。结论:丁丙诺啡透皮贴剂可以加快肩周炎患者的康复速度,提升肩周炎患者在治疗期间的生活质量。     

生物相容透皮给药微针治疗浅表肿瘤

复杂的肿瘤微环境导致抗肿瘤药物在肿瘤组织内递送效率低下，严重阻碍了药物对浅表肿瘤的治疗效果。生物相容透皮给药微针凭借较高的机械强度，刺穿皮肤角质层，将微针内的药物递送至浅表肿瘤组织内，提高生物利用度，改善静脉注射、口服给药的肝肾毒性等问题。本文介绍了生物相容透皮给药微针的设计及其在癌症化疗、光动力治疗、光热治疗、免疫治疗、基因治疗等领域的研究进展，对浅表肿瘤的微创、局部递药和精准、高效治疗具有重要指导意义。     

空心微结构透皮系统：为生物药品输药

最近几年,不少肽段和蛋白类药物上市。虽然这些药物的药效很高,但通常它们只能以静脉注射或者注射器注射的方式进行输药。这使得给药过程复杂化,而且不是每个病人都能顺应这种给药方式。同时,传统的透皮贴剂技术只能让亲脂性小分子化合物通过扩散透过角质层进入循环系统。满足这种给药方式的活性药物成分（API）非常少,对于生物药品来说更是少之又少。     

Low-frequency sonophoresis: a noninvasive method of drug delivery and diagnostics

Transdermal drug delivery offers an attractive alternative to injections and oral medications. However, applications of transdermal drug delivery are limited to only a few drugs as a result of low skin permeability. Application of low-frequency ultrasound enhances skin permeability, a phenomenon referred to as low-frequency sonophoresis. In this method, a short application of ultrasound is used to permeabilize skin for a prolonged period of time. During this period, ultrasonically permeabilized skin may be utilized for drug delivery. In addition, a sample of interstitial fluid or its components may be extracted through permeabilized skin for diagnostic applications. In this paper, we report our in vivo studies that demonstrate the principles of both of these concepts. Detailed studies on drug delivery are performed using inulin and mannitol as model drugs. Studies on diagnostics are performed using glucose as a model analyte. Applications of this technology to drug delivery and diagnostics are discussed.     

Perspectives on transdermal ultrasound mediated drug delivery

The use of needles for multiple injection of drugs, such as insulin for diabetes, can be painful. As a result, prescribed drug noncompliance can result in severe medical complications. Several noninvasive methods exist for transdermal drug delivery. These include chemical mediation using liposomes and chemical enhancers or physical mechanisms such as microneedles, iontophoresis, electroporation, and ultrasound. Ultrasound enhanced transdermal drug delivery offers advantages over traditional drug delivery methods which are often invasive and painful. A broad review of the transdermal ultrasound drug delivery literature has shown that this technology offers promising potential for noninvasive drug administration. From a clinical perspective, few drugs, proteins or peptides have been successfully administered transdermally because of the low skin permeability to these relatively large molecules, although much work is underway to resolve this problem. The proposed mechanism of ultrasound has been suggested to be the result of cavitation, which is discussed along with the bioeffects from therapeutic ultrasound. For low frequencies, potential transducers which can be used for drug delivery are discussed, along with cautions regarding ultrasound safety versus efficacy.     

Discovery of transdermal penetration enhancers by high-throughput screening

Although transdermal drug delivery is more attractive than injection, it has not been applied to macromolecules because of low skin permeability. Here we describe particular mixtures of penetration enhancers that increase skin permeability to macromolecules (approximately 1-10 kDa) by up to approximately 100-fold without inducing skin irritation. The discovery of these mixtures was enabled by an experimental tool, in vitro skin impedance guided high-throughput (INSIGHT) screening, which is >100-fold more efficient than current tools. In vitro experiments demonstrated that the mixtures delivered macromolecular drugs, including heparin, leutinizing hormone releasing hormone (LHRH) and oligonucleotides, across the skin. In vivo experiments on hairless rats with leuprolide acetate confirmed the potency and safety of one such mixture, sodium laureth sulfate (SLA) and phenyl piperazine (PP). These studies show the feasibility of using penetration enhancers for systemic delivery of macromolecules from a transdermal patch.     

Effect of physicochemical parameters on skin permeability of antihypertensive

Studies were carried out to establish a correlation of skin permeability with physicochemical parameters using five antihypertensive drugs. In vitro skin permeation was carried out in vertical type diffusion cells. When steady-state fluxes of the drugs were correlated with physicochemical properties, good correlation was obtained with the reciprocal of melting point. Weak correlation was obtained with partition coefficient, molecular weight and solubility. However skin permeability versus solubility profiles revealed an interesting trend. The initial permeation rates of the poorly water soluble drugs, prazosin hydrochloride and reserpine were higher than their steady-state fluxes and moderately water soluble drug atenolol showed more or less similar permeation throughout the entire span of the study. This trend changed gradually and reversed completely in the highly water soluble drug diltiazem hydrochloride. The study suggests that drug derivatives of low melting point and good aqueous solubility could be favorable candidates for transdermal delivery.     

Topical Cream-Based Dosage Forms of the Macrocyclic Drug Delivery Vehicle Cucurbit[6]uril

The macrocycle family of molecules called cucurbit[n]urils are potential drug delivery vehicles as they are able to form host-guest complexes with many different classes of drugs. This study aimed to examine the utility of Cucurbit[6]uril (CB[6]) in topical cream-based formulations for either localised treatment or for transdermal delivery. Cucurbit[6]uril was formulated into both buffered cream aqueous- and oily cream-based dosage forms. The solid state interaction of CB[6] with other excipients was studied by differential scanning calorimetry and the macrocycle''s transdermal permeability was determined using rat skin. Significant solid state interactions were observed between CB[6] and the other dosage form excipients. At concentrations up to 32% w/w the buffered aqueous cream maintained its normal consistency and could be effectively applied to skin, but the oily cream was too stiff and is not suitable as a dosage form. Cucurbit[6]uril does not permeate through skin; as such, the results imply that cucurbituril-based topical creams may potentially only have applications for localised skin treatment and not for transdermal drug delivery.     

Recovery of Skin Barrier After Stratum Corneum Removal by Microdermabrasion

Microdermabrasion is widely used as a non-invasive cosmetic technique that has recently been adapted to selectively remove stratum corneum to increase skin permeability for transdermal drug delivery. This study measured the kinetics of skin barrier recovery after stratum corneum removal using microdermabrasion in hairless guinea pigs. The skin was abraded at two sites on each animal, one of which was allowed to recover under occlusion while the other remained non-occluded. Histological measurements showed that skin barrier properties to sulforhodamine B largely recovered within 12 h, and the stratum corneum appeared largely reformed within 24 h for both occluded and non-occluded skin. Skin electrical resistance measurements showed significant recovery of the skin barrier within 24 h. We conclude that transdermal drug delivery may occur for up to 12 h after microdermabrasion in guinea pigs; however, humans will probably have a longer recovery time due to expected slower skin healing rates.     

The Experimental Evaluation and Molecular Dynamics Simulation of a Heat-Enhanced Transdermal Delivery System

Transdermal delivery systems are useful in cases where preferred routes such as the oral route are not available. However, low overall extent of delivery is seen due to the permeation barrier posed by the skin. Chemical penetration enhancers and invasive methods that disturb the structural barrier function of the skin can be used to improve transdermal drug delivery. However, for suitable drugs, a fast-releasing transdermal delivery system can be produced by incorporating a heating source into a transdermal patch. In this study, a molecular dynamics simulation showed that heat increased the diffusivity of the drug molecules, resulting in faster release from gels containing ketoprofen, diclofenac sodium, and lidocaine HCl. Simulations were confirmed by in vitro drug release studies through lipophilic membranes. These correlations could expand the application of heated transdermal delivery systems for use as fast-release-dosage forms.     

Transdermal delivery of scopolamine by natural submicron injectors: in-vivo study in pig

Transdermal drug delivery has made a notable contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. While transdermal delivery systems would appear to provide an attractive solution for local and systemic drug delivery, only a limited number of drugs can be delivered through the outer layer of the skin. The most difficult to deliver in this way are hydrophilic drugs. The aquatic phylum Cnidaria, which includes sea anemones, corals, jellyfish and hydra, is one of the most ancient multicellular phyla that possess stinging cells containing organelles (cnidocysts), comprising a sophisticated injection system. The apparatus is folded within collagenous microcapsules and upon activation injects a thin tubule that immediately penetrates the prey and delivers its contents. Here we show that this natural microscopic injection system can be adapted for systemic transdermal drug delivery once it is isolated from the cells and uploaded with the drug. Using a topically applied gel containing isolated natural sea anemone injectors and the muscarinic receptor antagonist scopolamine, we found that the formulated injectors could penetrate porcine skin and immediately deliver this hydrophilic drug. An in-vivo study in pigs demonstrated, for the first time, rapid systemic delivery of scopolamine, with T(max) of 30 minutes and C(max) 5 times higher than in controls treated topically with a scopolamine-containing gel without cnidocysts. The ability of the formulated natural injection system to penetrate a barrier as thick as the skin and systemically deliver an exogenous compound presents an intriguing and attractive alternative for hydrophilic transdermal drug delivery.     

Transdermal protein delivery by a coadministered peptide identified via phage display

Efficient transdermal drug delivery of large hydrophilic drugs is challenging. Here we report that the short synthetic peptide, ACSSSPSKHCG, identified by in vivo phage display, facilitated efficient transdermal protein drug delivery through intact skin. Coadministration of the peptide and insulin to the abdominal skin of diabetic rats resulted in elevated systemic levels of insulin and suppressed serum glucose levels for at least 11 h. Significant systemic bioavailability of human growth hormone was also achieved when topically coadministered with the peptide. The transdermal-enhancing activity of the peptide was sequence specific and dose dependent, did not involve direct interaction with insulin and enabled penetration of insulin into hair follicles beyond a depth of 600 microm. Time-lapse studies suggested that the peptide creates a transient opening in the skin barrier to enable macromolecular drugs to reach systemic circulation.