透皮给药研究的新进展

透皮给药安全可控,是无创给药的新途径,有着广阔的市场前景。现有的透皮药物限于小分子和低浓度,角质层屏障使大多数药物难以通过或难以达到有效浓度和有效速率。透皮给药的关键在于促进药物渗透,使药物透皮吸收进毛细血管。促渗手段有:使用化学促渗剂;对药物进行化学修饰制成前体药物;使用物理方法;将药物载入载体。这些方法的原理大致分为三种:改变角质层结构;外力驱动药物;将药物进行修饰或包裹。简要地介绍了增强药物透皮的物理方法和载体方法研究的新进展。     

驻极体促进药物透皮吸收的研究进展

近年来，经皮给药的促透方法和技术发展迅速，有关物理学、化学、药剂学的方法和技术的研究都很多。许多新方法和新技术的应用，使经皮给药系统逐渐成为一种成熟的给药方法。本文主要介绍驻极体透皮给药制剂的研究进展及其相关透皮机理。     

超声电导透皮给药与静脉给药后脑脊液及组织药物浓度相似

超声电导透皮给药是近年来国内外新兴的技术,临床广泛应用于内、外、妇、儿诸科疾病的治疗,它症状控制快,避免了全身用药的缺点,在较少的毒副作用下获得满意的疗效。我科应用超声电导靶向治疗仪和特制贴片进行了动物实验研究,旨在为超导给药的临床应用提供客观依据。1材料与方法1·1试药:水杨酸(北京化工厂,AR);头孢哌酮钠(白云山制药厂,批号0408051);头孢哌酮对照品,含量92·9%(中国药品生物制品鉴定所,420-9402);其他试剂均为分析纯。1·2仪器:Agilent1100型色谱仪。1·3动物与分组:家兔64只,平均体重(2·5±0·43)kg,随机分成2组,每组3…     

经皮给药系统的研究进展

经皮给药系统作为一种非侵入式药物递送系统,与传统的注射、口服等给药方式相比具有许多优势,非常适用于需要频繁治疗或长期治疗的疾病.根据近年来经皮给药系统的研究进展,对经皮给药机制、影响药物经皮渗透的因素、促进药物经皮吸收的方法进行归纳和评述,并对经皮给药系统的未来发展趋势进行展望.     

经皮给药电穿孔技术的研究

本项目研制了方波和指数两种类型的电穿孔仪。分别研究了盐酸丁卡因、萘普生和甲硝唑三种药物离体人皮和大鼠腹皮对电穿孔、被动扩散和离子导入的促渗对比实验。结果表明：电穿孔比被动扩散和离子导入有更高的药物经皮促渗作用;药物经皮渗透速率与脉冲数不成正比关系;指数波优于方波;共溶剂没有明显增加电穿孔促渗作用;促渗剂与电穿孔合用可以较大提高电穿孔单用促渗作用;经皮能量是控制药物经皮促渗的重要因素;电穿孔与离子导     

经皮给药电穿孔技术的新进展

经皮给药是药物三大给药方式之一，经皮给药的电穿孔技术是一种新的经皮给药技术。这种技术可以增强大分子药物的经皮渗透速率，具有许多潜在的优点，近年来倍受人们的重视。皮肤角质层是阻止的经皮渗透的主要屏障，在皮肤上施加高压脉冲，使角质层结构瞬间紊乱产生可的亲水性“电孔道”，以增加药物的经皮渗透速率。     

高致病性人禽流感H5N1透皮疫苗促渗剂的初步筛选

目的 初步筛选用于高致病性人禽流感H5N1透皮疫苗的较有效的促渗剂.方法 选用乙醇、丙二醇、二甲基亚砜、维甲酸、油酸作为促渗剂,将其应用于BALB/c小鼠,再用灭活的高致病性人禽流感H5N1透皮疫苗免疫小鼠,通过评价透皮免疫应答的效果对促渗剂进行初步筛选.结果 二甲基亚砜、维甲酸组和油酸组血清IgG抗体效价明显高于其他促渗剂组(P＜0.05).结论 在高致病性人禽流感H5N1透皮疫苗的小鼠模型中,二甲基亚砜、维甲酸和油酸是较好的促渗剂.     

经皮给药电穿孔技术的新进展

经皮给药是药物三大给药方式之一，经皮给药的电穿孔技术是一种新的经皮给药技术。这种技术可以增强大分子药物的经皮渗透速率，具有许多潜在的优点，近年来倍受人们的重视。皮肤角质层是阻止药物经皮渗透的主要屏障，在皮肤上施加高压脉冲，使角质层结构瞬间紊乱，产生可逆的亲水性“电孔道”，以增加药物的经皮渗透速率。这项技术对多钛和蛋白质药物制造业和临床医学有重要的意义     

低频超声透皮给药的研究进展与应用

低频超声可以增强包括大分子药物在内的许多药物的透皮传输,其主要机制是超声的空化作用,大多数人认为是通过改变角质层角化细胞排列结构来提高皮肤渗透能力的.低频超声透皮给药已被人们用于离体实验和动物活体实验,到目前为止,无论是小分子透皮传输还是大分子透皮传输都有很多成功的例子.但是真正通过低频超声透皮导入药物进行治疗的临床应用报道很少,需要更进一步大量的临床试验以确定其安全性与实用价值.一旦其安全性得以证实,合适的低频超声透皮仪研制成功,低频超声快速透皮必将成为一种安全、有效、可控、经济的新型给药方式.     

纳米控释系统的应用

纳米控释系统作为药物、基因传递和控释的载体 ,由于它的超微小体积 ,使其具有特殊的重要性。纳米粒子能穿透组织间隙和被细胞吸收 ,可在组织和细胞内驻留并长期释放药物 ,因此可用于许多特殊给药方式 ,如可用于介入方法导入血管内 ,可穿越血脑屏障导入脑内 ,口服后可被肠粘膜吸收并驻留在肠壁内 ,静脉注射可导向靶细胞 ,可将 DNA导入细胞浆质内。本文重点论述了纳米控释系统在药物和基因载体方面的应用 ,并作出展望     

The development of polyanhydrides for drug delivery applications

This paper reviews the development of the polyanhydrides as bioerodible polymers for drug delivery applications. The topics include design and synthesis of the polymer, physical properties, techniques to fabricate the polymer into drug delivery devices, evaluation of biocompatibility, and example applications of the polyanhydrides. Discussion of the interrelationship between the physical-chemical properties of the polyanhydrides, fabrication methods, and drug release rates is included. One section is devoted to a case study to provide a historical perspective of the development a polyanhydride-based drug delivery treatment from the conception of the idea to the final stages of human clinical trials. This section includes an outline of the extensive in vitro and in vivo testing that is necessary for development of a new material for biomedical applications.     

纳米粒子作为药物输送和药物控释体系的应用前景

纳米粒子作为药物和基因的载体显现出极大的潜力并被广泛研究。纳米粒子的超微小体积可使药物输送智能化,例如靶向定位地将药物投递到病灶局部或专一性地作用于靶细胞。纳米粒子的载体材料可屏蔽药物不良气味、维持药物长期缓慢释放、延长药物半衰期和减小毒副作用等。本文将从纳米药物输送、控释制剂的制备和应用前景等方面进行综述。     

Membrane-sealed hollow microneedles and related administration schemes for transdermal drug delivery

This paper presents fabrication and testing of membrane-sealed hollow microneedles. This novel concept offers the possibility of a sealed microneedle-based transdermal drug delivery system in which the drug is stored and protected from the environment. Sealed microneedles were fabricated by covering the tip openings of out-of-plane silicon microneedles with thin gold membranes. In this way a leak-tight seal was established which hinders both contamination and evaporation. To allow drug release from the microneedles, three different methods of opening the seals were investigated: burst opening by means of pressure; opening by applying a small voltage in the presence of physiological saline; and opening as a result of microneedle insertion into the skin. It was found that a 170 nm thick gold membrane can withstand a pressure of approximately 120 kPa. At higher pressures the membranes burst and the microneedles are opened up. The membranes can also be electrochemically dissolved within 2 min in saline conditions similar to interstitial fluid present in the skin. Moreover, through in vivo tests, it was demonstrated that 170 nm thick membranes break when the microneedles were inserted into skin tissue. The proposed concept was demonstrated as a feasible option for sealing hollow microneedles. This enables the realization of a closed-package transdermal drug delivery system based on microneedles.     

Fractional laser-assisted percutaneous drug delivery via temperature-responsive liposomes

Liposomes are used for transdermal delivery of drugs and vaccines. Our objective was to develop temperature-responsive (TR) liposomes to achieve temperature-dependent, controlled release of an encapsulated drug, and use fractional laser irradiation to enhance transdermal permeability of these liposomes. TR-liposomes prepared using a thermosensitive polymer derived from poly-N-isopropylacrylamide, N,N-dimethylacrylamide, egg phosphatidylcholine, and dioleoylphosphatidylethanolamine, delivered fluorescein isothiocyanate-conjugated ovalbumin (OVA-FITC) as a model drug. Effect of temperature on liposome size and drug release rate was estimated at two temperatures. Transdermal permeation through hairless mouse skin, with and without CO₂ fractional laser irradiation, and penetration into Yucatan micro-pig skin were investigated using Franz cell and fluorescence microscopy. Dynamic light scattering showed that mean liposome diameter nearly doubled from 190 to 325 nm between 37 and 50 °C. The rate and amount of OVA-FITC released from TR-liposomes were higher at 45 °C that those at 37 °C. Transdermal permeation of OVA-FITC across non-irradiated skin from both TR- and unmodified liposomes was minimal at 37 °C, but increased at 45 °C. Laser irradiation significantly increased transdermal permeation of both liposome groups at both temperatures. Fluorescence microscopy of frozen biopsy specimens showed deeper penetration of FITC from unmodified liposomes compared to that from polymer-modified liposomes. Rhodamine accumulation was not observed with polymer-modified liposomes at either temperature. Temperature-dependent controlled release of an encapsulated drug was achieved using the TR-liposomes. However, TR-liposomes showed lower skin permeability despite higher hydrophobicity. Fractional laser irradiation significantly increased the transdermal permeation. Additional studies are required to control liposome size and optimize transdermal permeation properties.     

A novel transdermal drug delivery system based on self-adhesive Janus nanofibrous film with high breathability and monodirectional water-penetration

Transdermal drug delivery systems (TDDS) had achieved significant success in medical practice, but still suffered from adhesion failure and skin reaction due to the occlusive properties of hydrophobic pressure sensitive adhesives (PSAs). In order to solve these problems, a novel TDDS patch based on self-adhesive Janus nanofibrous film was prepared by a multilayered electrospinning. This multifunctional patch was a bilayer structure. The subjacent layer was a hydrophobic and adhesive fibrous layer electrospun from polyacrylate PSA (HPSA), and the upper backing layer was a hydrophilic cross-linked poly (vinyl alcohol) (c-PVA) nanofibrous film. The structures of the HPSA/c-PVA composite fibrous films were characterized and their application properties, including adherence performance, water vapor permeability, water-penetration, release characteristics, and skin irritation were evaluated. The results indicated that the HPSA/c-PVA composite fibrous films could provide suitable adhesive properties for TDDS application, excellent capacity for drug loading and release, aesthetical appearance and high safety for use on the skin. Especially, due to the nanofibrous network structures and the hydrophobic–hydrophilic wettability gradient from hydrophobic HPSA layer to the hydrophilic c-PVA layer, the Janus films possessed high breathability and monodirectional water-penetration. Water could penetrate from the hydrophobic to the hydrophilic side, but could not permeate through in the opposite direction. This may provide a feasible solution to the problems caused by the water, sweat, or wound exudate on the skin, when the hydrophobic PSAs were used as matrix for TDDS and wound dressing patches.     

纳米控释系统在组织工程领域的应用

纳米控释系统作为药物、基因传递和控释的载体,由于它的超微小体积,使其具有特殊的重要性。对纳米控释系统在组织工程领域的研究进行评述,表明纳米粒子作为生长因子控制释放、信号分子传递和基因转染的载体在组织工程领域具有广阔的应用前景。     

Design of a multiple drug delivery system directed at periodontitis

Periodontal disease is highly prevalent, with 90% of the world population affected by either periodontitis or its preceding condition, gingivitis. These conditions are caused by bacterial biofilms on teeth, which stimulate a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The present research sought to demonstrate development of a multiple drug delivery system for stepwise treatment of different stages of periodontal disease. More specifically, multilayered films were fabricated from an association polymer comprising cellulose acetate phthalate and Pluronic F-127 to achieve sequential release of drugs. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. Different erosion times and adjustable sequential release profiles were achieved by modifying the number of layers or by inclusion of a slower-eroding polymer layer. Analysis of antibiotic and anti-inflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. The multilayered CAPP delivery system offers a versatile approach for releasing different drugs based on the pathogenesis of periodontitis and other conditions.     

Ultrasonically enhanced transdermal drug delivery. Experimental approaches to elucidate the mechanism

The effect of therapeutic range ultrasound on skin permeability was studied in vitro. Permeating molecule ionization state, pH, ultrasound duration, reversibility of the enhancement phenomenon, and skin structural alterations were evaluated. It was found that ultrasound affects the permeability of both ionized and unionized molecules. No irreversible structural alterations due to the ultrasound exposure were detected in the stratum corneum. Ultrasound enhancing mechanism was discussed.