载地塞米松聚合物胶束的制备及其性质

目的 制备具有良好生物相容性的地塞米松聚合物胶束,为血管炎症提供一种高效的治疗方法.方法 以聚己内酯-聚乙二醇载体和聚己内酯-聚甲基丙烯酸乙酯阳离子载体为材料制备地塞米松载药聚合物胶束.对所制备的载药聚合物胶束的形态、粒径、PDI、Zeta电位、包封率及载药量进行表征.以人脐静脉内皮细胞为细胞模型,采用噻唑蓝法考察载药...     

丁酰化甲壳素的制备及其生物相容性研究

目的 制备丁酰化甲壳素(Butyrylchitin, BC)并评价其生物相容性。方法 以甲壳素(Chitin, CT)为材料,正丁酸酐为酰化剂,高氯酸为催化剂制备BC。通过红光光谱、元素分析对BC进行表征,以小鼠成纤维细胞L929和Wistar大鼠为模型评价细胞毒性,组织相容性和降解性。结果 红光光谱、元素分析结果表明,甲壳素的羟基氢原子被取代,发生了丁酰化反应,取代度为1.96。细胞相容性评价结果显示,BC对小鼠成纤维细胞L929细胞生长没有影响,与对照组相比无显著性差异(P＞0.05)。体内降解性和组织相容性评价结果显示,BC膜片植入大鼠皮下和肌肉,降解缓慢,降解初期有一定的炎症反应,但总体表现出良好的组织相容性。结论 成功制备了BC,其具有良好的生物相容性。     

甲壳素衍生物神经导管的制备及其性质研究

目的 制备通透性良好的甲壳素衍生物神经导管,并研究其基本理化性质和生物相容性。方法 以碱化甲壳素为原料,涂层法制备不同醋酸钾含量的甲壳素衍生物神经导管;测定导管的吸水性、机械强度、通透性、降解性等;以 SD大鼠和RSC96细胞,评价神经导管的生物相容性。结果 神经导管的吸收性、机械强度、通透性因醋酸钾含量不同而变化。神经导管具备良好的组织相容性,降解炎症反应轻,对RSC96细胞具有较好的细胞相容性。     

生物可降解聚合物在医药领域中的应用

目的：综述生物可降解聚合物在医药领域中的应用及研究进展。方法：通过文献检索和查阅资料总结生物可降解聚合物的特性及临床应用。结果：理想的生物可降解聚合物应具有良好生物相容性、良好的生物降解性、降解时间和药物释放速率可调性；无毒性、不引起炎症和突变反应；释药体系的安全性高，制备工艺简单，无污染等。结论：经过临床研究表明，生物可降解聚合物在医药学上的应用给治疗技术带来了巨大的进步，生物可降解聚合物在体内不会残留，已用于许多医药领域，如癌症治疗、免疫培养、基因载体、制造纳米材料、研制人工器官、医疗器械、药物控释、辅料等方面；及人体修复用材料、医用胶黏剂、人工皮肤（伤口覆膜）、引导性组织再生材料、新型的可降解注射药物传递系统、药物控释系统、基因治疗载体、纳米药物载体、中药澄清剂、药剂的辅料，生物可降解聚合物还可用于人造泪液、隐形眼镜清洗液、合成生化试剂，眼药水基剂等。     

VaxInnate公司将透皮微针技术应用于流感疫苗给药制剂

美国VaxInnate公司日前获准（非独家）将3M药物制剂公司的透皮微针技术用于制备其开发的M2e通用型流感疫苗的透皮贴剂。3M公司的这种显微结构透皮系统技术采用了生物相容性聚合物微针,可避开皮肤角质层而将疫苗、蛋白质和肽类等药物注入机体,使用者几乎无不适感。这些大分子药物很难通过传统的透皮给药途径而进入机体。2008年7月3M公司的John Simons博士在国际缓控释学会会议上报告称,纳洛酮通过这种微针透皮贴剂可在约30秒内完成给药,其生物利用度与皮下注射给药相当。     

可溶性聚合物微针用于药物经皮递送的研究进展

目的： 了解国内外对于可溶性聚合物微针这一新型药物递送系统的研究进展，并对其优势及存在的问题进行分析，对发展前景进行展望。方法： 通过文献调研，总结可溶性聚合物微针的材料及功能，分析可溶性微针所解决的临床用药问题，以及各微针基质材料所具有的优势与面临的挑战。结果： 本文以临床不同的用药需求为视角进行分类，介绍了聚合物材料在可溶性微针递药系统中的应用，并对其优势及面临的挑战进行总结，对发展前景进行展望。结论： 目前对于可溶性聚合物微针的研究已取得了令人瞩目的进展。然而，为实现临床转化，可溶性聚合物微针递药系统的载药能力、安全性等方面仍然需要进一步的研究。     

天然高分子聚合物胶束的研究进展

聚合物胶束作为药物载体,具有稳定性好,增加难溶性药物溶解度,使药物靶向肿瘤部位并缓慢释放,降低不良反应,提高药物生物利用度等优点,是一种优良的载药系统。天然高分子材料由于来源丰富,生物相容性好,降解产物对人体无毒而备受重视。通过查阅文献,笔者综述了天然高分子材料聚合物胶束的研究进展。     

脂质聚合物杂交纳米粒的研究进展

脂质聚合物杂交纳米粒（Lipid polymerhybrid nanoparticles,LPHNPs）是一种新型载药系统,该纳米粒由修饰亲水性聚合物的脂质外壳包裹疏水性聚合物内核组成,LPHNPs具有较高的结构完整性、良好的生物相容性和载药量及制备材料多样化等优点,使得其在药物递送、诊断成像、基因治疗领域被广泛研究。现主要对LPHNPs的基本特点、结构、制备方法及应用进行综述,以期为后续研究提供参考。     

空心微针透皮给药技术的研究进展

空心微针类似于微米级的注射针,具有注射给药和透皮给药的双重特点.作为一种新型的透皮给药技术,空心微针近年来在疫苗和胰岛素等生物大分子药物的递送方面显示出极大的潜力.笔者根据近年来国内外相关的研究报道,对空心微针的促透机制、常用制备材料及工艺和在透皮给药中的应用等进行归纳总结,以期为空心微针技术的研究和发展提供参考借鉴.     

甲壳素的乙酰化制备及生物相容性评价

目的 制备乙酰化甲壳素（Acetylated Chitin,AC）并评价其生物相容性。方法 通过乙酸酐和乙酸混合体系制备AC。通过红外光谱和元素分析对AC进行表征,以L929细胞和Wistar大鼠为模型评价AC的细胞相容性和组织相容性。进行溶血实验检测AC的血液相容性。结果 红外光谱和元素分析结果显示,甲壳素的乙酰化反应发生在C3和C6位点,AC产物的酰化度为1.92。生物相容性评价结果显示,AC膜片的细胞毒性评级为0级;在肌肉组织植入初期有轻度炎症反应,降解速度缓慢;溶血率<5%,有良好的血液相容性。结论 成功制备了AC,并且其总体上具有良好的生物相容性。     

Polymer Coated Polymeric (PCP) Microneedles for Controlled Delivery of Drugs (Dermal and Intravitreal)

Microneedles are used to deliver drugs topically across the skin and mucous membranes. Dissolvable microneedles are made using soluble polymers, which disintegrates in the tissue and release the entire payload instantaneously including the polymer construct. Often, a slow release of drug into the tissue is desirable to overcome the severity of side effects at the site of administration as well as systemic adverse effects. In addition, controlled release of active pharmaceutical ingredient (API) only (not the excipients) is safe and effective particularly when the drug delivery is intended to sensitive organs like the eye. In this project, the feasibility of fabricating polymer coated polymeric (PCP) microneedles to achieve a gradual release of only the active ingredient from the device was investigated. The potential application of such PCP microneedles in the dermal and intravitreal drug delivery was also explored using animal tissue models. The PCP microneedles were found to be intact even after prolonged contact with the release medium. The time at which 50% (T50%) of dextran (10 K) was released in case of microneedles prepared using 20% of core polymer (PVP-K30) was about 15 min versus less than 5 min in the case of uncoated microneedles. Whereas when the core polymer concentration was increased to 50%, the T_50% was increased to 90 min. The rate of release depended on the polymer molecular weight grade. The rate of drug release was not influenced by the total amount of concentration of dextran. The PCP microneedles of lidocaine hydrochloride could constantly release the drug for up to 9 h in the skin tissue. Likewise, the PCP microneedles infused voriconazole, intravitreally for 6 h.     

Fabrication of Dissolving Polymer Microneedles for Controlled Drug Encapsulation and Delivery: Bubble and Pedestal Microneedle Designs

Dissolving microneedle patches offer promise as a simple, minimally invasive method of drug and vaccine delivery to the skin that avoids the need for hypodermic needles. However, it can be difficult to control the amount and localization of drug within microneedles. In this study, we developed novel microneedle designs to improve control of drug encapsulation and delivery using dissolving microneedles by (i) localizing drug in the microneedle tip, (ii) increasing the amount of drug loaded in microneedles while minimizing wastage, and (iii) inserting microneedles more fully into the skin. Localization of our model drug, sulforhodamine B in the microneedle tip by either casting a highly concentrated polymer solution as the needle matrix or incorporating an air bubble at the base of the microneedle achieved approximately 80% delivery within 10 min compared to 20% delivery achieved by the microneedles encapsulating nonlocalized drug. As another approach, a pedestal was introduced to elevate each microneedle for more complete insertion into the skin and to increase its drug loading capacity by threefold from 0.018 to 0.053 μL per needle. Altogether, these novel microneedle designs provide a new set of tools to fabricate dissolving polymer microneedles with improved control over drug encapsulation, loading, and delivery.     

Considerations in the use of microneedles: pain,convenience, anxiety and safety

Transdermal delivery using microneedles is gaining increasing attention from pharmaceutical and cosmetic companies as one of the promising drug delivery methods. Microneedle products have recently become available on the market, and some of them are under evaluation for efficacy and safety. To be available in the market for cosmetic and therapeutic use, several factors should be considered, including pain, anxiety, convenience and safety. These factors are summarized and reviewed in this article according to type of microneedle. Various kinds of materials have been used for manufacturing microneedles and developing drug formulations for microneedles. Safety information about materials used for microneedles is summarized in terms of type of microneedles. In addition to their biocompatibility, mechanical safety is also discussed. This review can provide guidelines for designing microneedle products for proper use.     

Microneedles: an emerging transdermal drug delivery system

Objectives One of the thrust areas in drug delivery research is transdermal drug delivery systems (TDDS) due to their characteristic advantages over oral and parenteral drug delivery systems. Researchers have focused their attention on the use of microneedles to overcome the barrier of the stratum corneum. Microneedles deliver the drug into the epidermis without disruption of nerve endings. Recent advances in the development of microneedles are discussed in this review for the benefit of young scientists and to promote research in the area. Key findings Microneedles are fabricated using a microelectromechanical system employing silicon, metals, polymers or polysaccharides. Solid coated microneedles can be used to pierce the superficial skin layer followed by delivery of the drug. Advances in microneedle research led to development of dissolvable/degradable and hollow microneedles to deliver drugs at a higher dose and to engineer drug release. Iontophoresis, sonophoresis and electrophoresis can be used to modify drug delivery when used in concern with hollow microneedles. Microneedles can be used to deliver macromolecules such as insulin, growth hormones, immunobiologicals, proteins and peptides. Microneedles containing ‘cosmeceuticals’ are currently available to treat acne, pigmentation, scars and wrinkles, as well as for skin tone improvement. Summary Literature survey and patents filled revealed that microneedle‐based drug delivery system can be explored as a potential tool for the delivery of a variety of macromolecules that are not effectively delivered by conventional transdermal techniques.     

微针经皮给药技术

微针是介于皮下注射和透皮贴剂之间的一种给药方式,利用在皮肤角质层产生的微小孔道来显著增加药物的经皮吸收。综述微针经皮给药技术的研究进展,介绍制造微针的材料和方法、微针的给药方式及其在经皮给药系统中的应用。     

Polymer Microneedles for Controlled-Release Drug Delivery

Purpose As an alternative to hypodermic injection or implantation of controlled-release systems, this study designed and evaluated biodegradable polymer microneedles that encapsulate drug for controlled release in skin and are suitable for self-administration by patients. Methods Arrays of microneedles were fabricated out of poly-lactide-co-glycolide using a mold-based technique to encapsulate model drugs—calcein and bovine serum albumin (BSA)—either as a single encapsulation within the needle matrix or as a double encapsulation, by first encapsulating the drug within carboxymethylcellulose or poly-l-lactide microparticles and then encapsulating drug-loaded microparticles within needles. Results By measuring failure force over a range of conditions, poly-lactide-co-glycolide microneedles were shown to exhibit sufficient mechanical strength to insert into human skin. Microneedles were also shown to encapsulate drug at mass fractions up to 10% and to release encapsulated compounds within human cadaver skin. In vitro release of calcein and BSA from three different encapsulation formulations was measured over time and was shown to be controlled by the encapsulation method to achieve release kinetics ranging from hours to months. Release was modeled using the Higuchi equation with good agreement (r² ≥ 0.90). After microneedle fabrication at elevated temperature, up to 90% of encapsulated BSA remained in its native state, as determined by measuring effects on primary, secondary, and tertiary protein structure. Conclusions Biodegradable polymer microneedles can encapsulate drug to provide controlled-release delivery in skin for hours to months.     

微针在儿童经皮递药中的研究进展

与传统的口服和肠外给药途径相比,经皮给药系统作为一种非侵入性替代方法非常有吸引力。特别对于儿童患者,它有助于克服该群体特有的问题,如吞咽困难、口服制剂的适口性以及与针头相关的恐惧和疼痛。然而,儿童的皮肤屏障功能有效地限制了药物的经皮吸收。微针可突破皮肤最外层的角质层,增加经皮给药的药量。过去几十年,以微针为基础药物输送系统的研究取得了显著进展。与微针相关的研究论文呈指数级激增。本文概括了微针的分类及特点,讨论了微针在儿童经皮递药中的研究进展,最后对微针介导的儿童经皮递药的未来前景进行了简要展望。     

Bleomycin-Coated Microneedles for Treatment of Warts

Purpose

Bleomycin-coated microneedles were devised for delivery of bleomycin into the sub-epidermal skin layer for the treatment of warts in order to provide patient convenience and reduce patient pain and fear.

Method

Poly-lactic-acid (L-PLA) microneedles were fabricated by a molding process and then the tips were partially coated using a dip-coating method based on a microstructure well. The mechanical strength of the pre-coated polymer microneedles was observed by inserting them in porcine foot and back skin. The holes were stained with trypan blue and the mechanical failure of the microneedles was investigated using a scanning electron microscope (SEM). The initial distribution of a model drug using microneedles was compared with distribution by intralesional injection. The amount of drug leaked below the skin using microneedles was measured and compared with that leaked by intralesional injection. The pharmacokinetic properties of bleomycin-coated microneedles were studied. The bleomycin remaining on the coated microneedles after the in vivo pharmacokinetic study was measured.

Results

Bleomycin was successfully coated on the tips of L-PLA microneedles. More than 80% of the bleomycin dissolved into the skin in vitro within 15 min. L-PLA microneedles possessed sufficient mechanical strength to penetrate skin with a thick stratum corneum. Compared to intralesional injection, tip-coated microneedles were more effective in distributing a drug into the sub-epidermal skin layer. A pharmacokinetic study of bleomycin-coated microneedles showed 50 min of T_max.

Conclusions

Bleomycin-coated microneedles appeared to be a convenient and painless alternative to conventional intralesional injection of bleomycin. The microneedles delivered bleomycin into the targeted dermal layer regardless of body site. Bleomycin-coated microneedles therefore provide a suitable method for the treatment of warts.