Microneedles, as a new efficient and safe transdermal drug delivery technology, has a wide range of applications in drug delivery, vaccination, medical cosmetology, and diagnostics. The degree of microneedles penetration into the skin determines the reliability of the delivery dose, but its evaluation is not yet well-established, which is one of the major constraints in the commercialization of microneedles. In this paper, a novel visual simulated skin model was developed with reference to the physical properties of real skin. The simulated skin model was well-designed and its prescription was optimized to make the thickness, hardness, elasticity, and other parameters close to those of real skin. It not only meets the need to assess the degree of insertion of microneedles but also provides a visual observation of the insertion state of microneedles.

As a kind of nanovesicles, liposomes are considered to be the most promising delivery vehicles for drugs and vaccines. The preparation of liposomes using microfluidic chips is one of the most effective and feasible methods. Removal of solvents and non-encapsulated drugs is usually required after liposome formation, which will affect the storage stability and medical safety of liposomes, thus hindering their industrial production and clinical application. Therefore, innovative preparation techniques with multiple integrated functions are of practical significance to address the challenges of traditional and latest developed liposome preparation technologies. A novel three-dimensional integrated microfluidic device (3D-mf device) reported here can be used as a continuous process flow system for liposome preparation and purification. The microchannel array of the microdevice is 4 x 3, and the computational fluid dynamics simulation is used to determine that the ratio of the four filter area channels is 1: 0.75: 0.5: 0.2. Drug-loaded liposomes with an average particle size of 208 nm and polydispersity index (PDI) of 0.211 were prepared by adjusting the total flow rate (TFR) and flow rate ratio (FRR). The removal rates of ethanol and polyinosinic acid: polycytidylic acid [poly (I: C)] after a single cycle were 66.8 % and 56.3 %, respectively. The size distribution and zeta potential of liposomes keep stable within 28 days. Finally, in an immunization study in rats, hemagglutination inhibition titers (HI, >= 512) were found to be significantly higher than those required for protection after two rounds of immunization with 6 mu g of hemagglutinin from a split influenza vaccine with poly (I: C) liposomes. This innovative integrated device shows the potential for industrial production of nano-pharmaceutical applications.

Mucosal delivery systems have gained much attention as effective way for antigen delivery that induces both systemic and mucosal immunity. However, mucosal vaccination faces the challenges of mucus barrier and effective antigen uptake and presentation. In particular, split, subunit and recombinant protein vaccines that do not have an intact pathogen structure lack the efficiency to stimulate mucosal immunity. In this study, poly (lactic acid-co-glycolic acid-polyethylene glycol) (PLGA-PEG) block copolymers were modified by mannose to form a PLGA-PEG-Man conjugate (mannose modified PLGA-PEG), which were characterized. The novel nanoparticles (NPs) prepared with this material had a particle size of about 150 nm and a zeta potential of -15 mV, and possessed ideal mucus permeability, immune cell targeting, stability and low toxicity. Finally, PLGA-PEG-Man nanoparticles (PLGA-PEG-Man NPs) were successfully applied for intranasal delivery of split influenza vaccine in rat for the first time, which triggered strong systemic and mucosal immune responses. These studies suggest that PLGA-PEG-Man NPs could function as competitive potential nano-adjuvants to address the challenge of inefficient mucosal delivery of non-allopathogenic antigens.

The preparation of nanofiber materials by electrospinning and the fabrication of microneedle arrays patch for medical and cosmetic purposes using polymer materials are hotspots in the basic and applied research of materials science in recent decades, showing a bright future. However, the mechanical strength of polymer microneedles is relatively weak, and the performance of piercing the skin determines their effectiveness and reliability. A novel multilayered fibrous membrane prepared by electrospinning has been developed with similar mechanical properties to those of real skin, which is made of interwoven elastic fibers. It can replace real skin and exhibits more accuracy, simplicity, and rapidity for in vitro evaluation of microneedle insertion properties compared to some other methods.

Nasal mucus is the primary barrier affecting the nasal absorption of vaccines and drugs. In vivo assessments are difficult to perform due to the complexity and variability of the confounding factors, whereas in vitro evaluations are mostly used. The existing in vitro assays for monitoring nasal mucus permeability of drugs, such as cell model assays and multiparticle tracer techniques, have the disadvantages of a long cell culture cycle, cumbersome operation, high cost, little available information, and the need for fluorescent labelling, which have great limitations for the in vitro evaluation of nasal mucosal formulations. Therefore, there is an in urgent need to establish a rapid, simple and sensitive method for the evaluation of mucus permeability of nasal mucosal formulations. Based on the sensitivity of ATR-FTIR spectroscopy to changes in drug structure and mucin secondary structures, the nasal mucus permeability of liposomes, typical lipid nanoparticles, with different properties (particle size and charge) was studied in this paper, and the interaction of different liposomes with mucin in mucus by FTIR spectra to establish an in vitro evaluation method for mucus permeability of nasal mucosal preparations. Methodological studies showed that for PEG10000, chitosan, and sodium alginate liposomes, the linear relationships of the method were Y=2.386 6X+2.154, Y=1.870 3X+0.278 9, Y=1.130 14X+0.060 9, the linear correlation coefficients were 0.995 8,0.994 5,0.990 9, and the precision RSD values were 0.62%, 0.73%, and 0.95%, respectively; the RSD values in the repeatability experiment were 0.83%, 0.97%, and 0.88%, respectively. It is indicated that the method has a good linear relationship, high precision, and good repeatability and can be used to evaluate the permeability of pharmaceutical preparations in mucus in vitro. The results showed that the sample absorption bands with increasing intensity of different liposome formulations could be obtained by scanning the samples at different times in interaction with mucus using ATR-FTIR. For PEG liposomes with different particle sizes, the smaller the particle size, the stronger the mucus permeability; for liposomes with different charges, chitosan liposomes with positive charges have the weakest mucus permeability, followed by sodium alginate and PEG liposomes have the strongest mucus permeability. Further studies have shown that the difference in mucus permeability of liposomes with different charges stems from their interaction with mucins, and this conclusion can be obtained by analyzing the information on each secondary structure (alpha-helix, beta-sheet, beta-turn, irregular turn) contained in the mucinamide I band (1 600 similar to 1 700 cm(-1)). In summary, the in vitro evaluation method established in this paper based on ATR-FTIR is sensitive and simple and can be used as a rapid assay of nasal mucus permeability for various preparations. And with improved applicability, it can also be used to evaluate the permeability of pharmaceutical preparations in other mucus, which has a broad application prospect.

In order to alleviate the pain associated with subcutaneous injections, microneedles (MNs) are gaining increasing attention as a novel transdermal drug delivery modality. Among them, porous microneedles (pMNs) are particularly suitable for the delivery of drugs and vaccines whose activity is sensitive to the microneedle preparation process. They can carry drugs actively to achieve an effective load and deliver drugs into the skin. In this study, the biocompatible cellulose acetate (CA) microporous MNs with a large pore size of 1.13 μm ± 0.45 and a high porosity of 74.8% ± 2.8% were prepared by using a safe nonsolvent-induced phase separation (NIPS) method. The MN patches prepared after adsorption of appropriate concentrations of split influenza vaccine fully met the dose loading requirements. A biocompatible carboxymethyl cellulose (CMC) solution was used in the pMN coating to strengthen their mechanical properties, with an average maximum stress of 32.89 N, and to act as a medium for the dispersion of an adjuvant in the coating layer. The influenza vaccine adsorbed in the micropore and the adjuvant dispersed in the coating were released intradermally to exert synergistic effects with different release patterns and rates. The coated pMNs induced an efficient immune response in Wistar rats with a hemagglutination inhibition (HI) titer of ≥1024, which was comparable to that of intramuscular injection. The research is organized around the goal of engineering exploration of innovative technologies, suggesting that pMNs have a tantalizing prospect for future applications. It opens up the possibility of eventually obtaining a simple, easy-to-use, and efficient application technology for the prevention of global epidemics like influenza.

The use of microneedles (MNs), an innovative transdermal technology, enables efficient, convenient, painless, and controlled-release drug delivery. Porous microneedles (pMNs), special MNs with abundant interconnected pores that can produce capillary action, are gaining increasing attention as a novel MNs technology. pMNs can actively adsorb bioactive ingredients from solutions of drugs or vaccines for in vivo delivery or from interstitial skin fluids (ISFs) for wearable and point-of-care testing (POCT) products. Different pore sizes and porosities of pMNs can be achieved with different materials and preparation processes, which makes the application of pMNs adaptable to multiple scenarios. In addition, easier and faster detection will be accomplished by the smart combination of pMNs with other detection technologies. This paper aims to summarize the recent research progress of pMNs, focusing on the influence of various materials and their corresponding preparation methods on its structure and function display, discussing the key issues and looking forward to the future development.

In recent years, microneedles have received a lot of attention from researchers because of its advantages of being painless and minimally invasive, safe and efficient. Microneedles have been widely used in the fields of transdermal drug delivery, medical aesthetics and biological diagnosis. However, traditional microneedles, especially those prepared directly from polymer materials, generally have problems such as low mechanical strength, single drug release mode, poor biological sensing performance and simple functions. The clever combination of nanotechnology and microneedles can effectively improve the above problems, due to the unique nano-size, mechanical strength and photoelectric effects of nanoparticles. This paper reviews nanoparticles for microneedles, including inorganic nanoparticles（metal, inorganic non-metal）, organic nanoparticles（polymer, lipid） and drug nanoparticles（nanocrystalline drugs, virus-like particles）, and describes the role of nanoparticles in increasing mechanical property, synergistic improvement of drug release and immune enhancement are introduced. Finally, the urgent problems need to be solved in this field and the future research directions are discussed.

The emergence of microneedle arrays (MNAs) as a novel, simple, and minimally invasive administration approach largely addresses the challenges of traditional drug delivery. In particular, the dissolvable MNAs act as a promising, multifarious, and well-controlled platform for micro-nanotransport in medical research and cosmetic formulation applications. The effective delivery mostly depends on the behavior of the MNAs penetrated into the body, and accurate assessment is urgently needed. Advanced imaging technologies offer high sensitivity and resolution visualization of cross-scale, multidimensional, and multiparameter information, which can be used as an important aid for the evaluation and development of new MNAs. The combination of MNA technology and imaging can generate considerable new knowledge in a cost-effective manner with regards to the pharmacokinetics and bioavailability of active substances for the treatment of various diseases. In addition, noninvasive imaging techniques allow rapid, receptive assessment of transdermal penetration and drug deposition in various tissues, which could greatly facilitate the translation of experimental MNAs into clinical application. Relying on the recent promising development of bioimaging, this review is aimed at summarizing the current status, challenges, and future perspective on in vivo assessment of MNA drug delivery by various imaging technologies.

The force, speed and depth of microneedle array penetration process are usually used to evaluate the degree and efficiency of its penetration into the skin. The skin is the basis of its performance evaluation. The physical properties of the skin are mainly determined by the combination of keratin filaments, collagen fibers, elastic fibers and subcutaneous tissues, and reflect its impact on microneedle penetration from dimensions such as thickness, elasticity, hardness and toughness. Mechanical, permeable, tissue and barrier skin models are used to explain and simulate this aspect of real skin functions. Similarly, various skin mechanics models including constitutive models established after skin mechanics analysis also analyze the mechanical characteristics of the skin from the physical dimension. Real skin is complicated, with large differences, difficult access and storage, and some ethical issues. Skin model can replace real skin assisted to a certain extent for the design, development and performance evaluation of microneedle delivery system. The material involved in the model may be different from the physical properties of the real skin, it cannot fully simulate the chemical composition and distribution of the real skin, the tissue structure, and the interaction between the skin tissue and other tissues. However, the skin model can be easily adjusted by changing those characteristic materials comparable to the skin and form a simulation system. As for microneedle evaluation, it is more necessary to consider the mechanical properties of the skin and the skin model. The skin model needs to have a surface barrier that is difficult to puncture like the stratum corneum, and the hardness, elasticity and toughness under the barrier are similar to the real skin to simulate the reaction force after the microneedle penetration. In these aspects, the simulation of a single performance is relatively easy to achieve, but it is not easy to achieve a comprehensive performance similar to the real skin. The application of advanced methods with higher resolution, accurate quantitative and real-time dynamic evaluation of the penetration force and penetration rate of microneedle puncture can help us systematically and accurately analyze microneedle penetration behavior, and the development and application of 3D skin tissue engineering products that are closer to the composition, structure and physical properties of real skin can provide an effective solution path to help establish a more economical and applicable skin model. The establishment of a standardized evaluation model will undoubtedly help advance related research and promote the better industrialization and commercial application of microneedle array technology. In addition, the inherent hardness difference caused by different materials constructed by microneedles, such as metal, monocrystalline silicon and polymer materials, may have a corresponding difference in the penetration rate and penetration depth of real skin or skin model, but this can be solved by providing differentiated judgment methods for different rigid microneedles and formulating different indicators when setting skin model. Therefore, there is no need to design a special skin model to evaluate the puncture behavior of different microneedle.

Objective:To optimize the challenge scheme for establishing a stable mouse model of Artemisia annua pollen-induced allergic rhinitis. Methods:BALB/c mice were subcutaneously injected with 0.1 ml allergen extract containing 20 μg/ml Art a1 from Artemisia pollen on 1 d, 4 d and 7 d. One week after the sensitization, these mice were divided into three groups and intranasally challenged with Artemisia annua pollen allergen extract containing 500 μg/ml Art a1 for 7 (7 d group), 10 (10 d group) and 14 (14 d group) consecutive days, respectively. The first challenge was followed by another 7 days of challenge every four weeks. Blank control group was set up through sensitizing and challenging BALB/c mice with normal saline. Behavioral changes and nasal pathological changes were observed. The changes in humoral and cellular responses were also detected. After the first challenge cycle was decided, the challenge frequency was further optimized. Results:After the first challenge, the allergic symptoms of mice in 10 d group were significantly severe than those in 7 d and 14 d groups, and the levels of serum specific IgE antibody in 10 d and 14 d groups were significantly higher than that in 7 d group. After the second challenge, the mice in the three model groups still had obvious allergic symptoms as compared with the blank control group. There were obvious pathological changes in the nose, including epithelial cell proliferation, turbinate enlargement and inflammatory cell increase. Moreover, the level of serum specific IgE antibody increased significantly and the proliferation of antigen-specific IL-4 and IL-6 lymphocytes was significantly up-regulated, especially in 10 d and 14 d groups. The frequency of challenge had a great impact on the stability of the allergic model. The allergic symptoms of sensitized mice challenged every two weeks were significantly severe than those of mice challenged every four weeks and the level of serum antigen-specific antibody was also higher.Conclusions:This study optimized the first challenge cycle and challenge frequency for establishing a mouse model of Artemisia annua pollen-induced allergic rhinitis, which provided reference for the establishment of drug efficacy evaluation system for desensitization therapy.

Over the past decades, the use of microneedles, a unique transdermal drug delivery technology, to deliver drugs to the skin for biological effects has been very active, and the interest in dissolving microneedles in this field has also increased rapidly. However, ensuring the effectiveness of microneedles requires attention to several key steps. The microneedle must pierce the stratum corneum first, and then continue to penetrate to a certain depth under the action of applied force, without bending or breaking during the puncture process, to ensure the accurate and controllable delivery of the microneedles. In the process of microneedle penetration, the skin is easily deformed due to its elasticity, and the microneedle often cannot penetrate the skin completely, which reduces the delivery efficiency of the microneedle and limits the application of the microneedle in drug delivery, especially for dissolving microneedles whose mechanical strength is weaker than that of metal and monocrystalline silicon microneedles. The delivery efficiency of the microneedle is mainly related to the penetration depth of the microneedle, which in turn is related to factors such as the mechanical properties of the skin, the structure of the microneedle, and the way of administration. Clearly, there are still many technical challenges to make the effectiveness of dissolving microneedles in line with requirements of clinical medication. Therefore, it is necessary to systematically review the influencing factors of the penetration depth of the dissolving microneedles and the methods to improve the delivery efficiency. Technological improvement strategies suitable for enhancing the drug delivery efficiency of dissolving microneedles will certainly contribute to more accurate delivery of bioactive ingredients to the body and a wider range of medical applications.

本文主要研究纳米粒对可溶性微针机械性能的影响,从而构建优异机械性能的可溶性微针.采用不同种类的纳米材料(碳酸钙、羟基磷灰石、二氧化硅)、粒径(20、60、100nm)和处方质量占比(2％、6％、10％),与微针基质材料[聚乙烯吡咯烷酮(PVP)、乙烯基吡咯烷酮-乙酸乙烯酯共聚物(PVP/VA)]共混形成可溶性微针.通过纳米压痕仪研究纳米粒对微针弹性模量以及硬度的影响.纳米碳酸钙对PVP微针的弹性模量与硬度均有显著性提高(P＜0.001);纳米羟基磷灰石对PVP/VA微针的弹性模量与硬度均有显著性提高(P＜0.001).当纳米羟基磷灰石粒径为20 nm时,PVP/VA微针的弹性模量为(10.6±1.0)GPa,硬度为(0.47±0.06)GPa,且随纳米粒粒径增大,微针机械性能降低;当纳米羟基磷灰石质量占比从2％至6％,PVP/VA微针的弹性模量与硬度得到显著性提高(P＜0.001),但继续提高占比对微针的影响不大.纳米羟基磷灰石增强的PVP/VA可溶性微针对完好皮肤无刺激性影响,对破损皮肤有轻微刺激性,但在72 h后完全消失.动物实验已获得浙江工业大学实验动物福利与伦理委员会批准.因此,纳米羟基磷灰石增强的PVP/VA可溶性微针具有良好的生物安全性.综上可知,根据给定的基质材料构建微针时,需选择合适的纳米粒、粒径以及处方质量占比,才能有效且显著地提升微针机械性能.

微针作为一种微创、安全和高效的新型经皮给药技术,受到越来越多的关注.微针在皮肤表面形成的孔道是该技术递送药物的前提和关键,但目前缺少对皮肤孔道的系统性评价.本文综述了有关微针致皮肤孔道形成与闭合的影响因素及评价方法,涉及微针几何参数、制备材料、药物、刺入参数、受试者皮肤差异和有无闭塞等方面因素,为微针应用的有效性和安全性提供参考和借鉴.

研究了制备工艺对可溶性微针的机械、穿刺和吸湿性能的影响,并优化微针的制备工艺.采用Plackett?Burman设计筛选主要影响因素,运用Box?Behnken设计?响应面法优化微针的制备工艺.通过3D显微镜和扫描电子显微镜观察微针的外观形态,石蜡膜穿刺法评估微针的穿刺性能,称重法考察微针的吸湿性能,物性分析仪表征微针的机械性能,组织学切片验证微针穿刺皮肤的可行性.结果表明,微针韧脆材料比(P=0.0023)、药物占比(P=0.0075)、固化温度(P=0.0013)、空气流速(P=0.0027)和离心时间(P=0.0028)对穿刺性能具有显著影响;微针韧脆材料比(P=0.0177)对机械性能具有显著影响;各种因素对吸湿性能无显著影响.最优微针制备工艺参数为:韧脆材料比:9,50,药物占比:6.0％,溶媒占比60％,离心转速4000 r/min,离心时间28 min,离心温度25℃,干燥温度38℃,干燥湿度10％,空气流速0.5 L·min-1,微针的刺入深度为(412.03±2.85)μm,与预测值的偏差小于1％.最优微针的应力可达1.3 N/针,可成功刺破角质层.

目的:改进组织残留量法冲洗装置,建立更适宜测定鼻黏膜递送凝胶制剂组织粘附性的方法.方法:根据鼻黏液的流变学性质,筛选适宜模拟鼻黏液为黏膜冲洗液,以1.0 mL· min-1的流速冲洗模拟鼻黏液进行组织残留量实验.设计自制冲洗装置并与溶出仪进行比较.同时对比称重法和荧光示踪法对凝胶定量的精密度.结果:以新鲜鸡蛋壳膜为模拟鼻黏膜,在与真实鼻黏液固形物相同的情况下,比较多种模拟黏液剪切速率与黏度的变化趋势后发现,羟乙基纤维素(HEC)-溶菌酶溶液具有剪切变稀的性质,但黏度约为20mPa·s,比真实鼻黏液偏高,且该溶液不稳定,久置后出现大量絮状沉淀.黏蛋白-溶菌酶各1％溶液和HEC-明胶各1％溶液的黏度接近(约13 mPa·s),即与健康的人鼻黏液黏度一致.但只有HEC-明胶溶液久置后稳定无沉淀生成,具有与健康人鼻黏液最相似的流变学性能,且溶液的荧光强度在测定时间段内稳定(21 ～22 a.u.),符合试验要求.在对组织残留量测定的方法中,以异硫氰酸荧光素标记的牛血清白蛋白(FITC-BSA)为探针的荧光探针法定量测定的RSD在5％～10％,不仅小于称重法结果,也满足《中华人民共和国药典》要求.使用实验自制装置进行冲洗和荧光示踪法时,组内组织残留量的RSD在5％～ 10％,重复性好.结论:使用自制冲洗装置,以HEC-明胶溶液作为黏膜冲洗液,荧光示踪法定量测定温敏凝胶在用于药物鼻黏膜递送过程中的组织残留量,这一方法简便可靠.

本文主要研究金属和可溶性微针对皮肤微孔道形成与闭合的影响因素及效果.采用不同长度、针尖间距和基座面积的金属(不锈钢)微针,形状分别为铅笔形和圆锥形,以及不同针尖间距的铅笔形可溶性微针.将微针刺入在除毛小鼠和大鼠的皮肤上,通过经皮水分丢失(transepidermal water loss,TEWL)法和亚甲蓝染色法研究微针施用参数、自身参数和动物对孔道产生的影响;通过视觉观察微针引起的皮肤局部刺激性现象.动物实验已获得浙江工业大学实验动物福利与伦理委员会批准.不锈钢金属微针刺入皮肤后保持30 s以上,刺入力分别为2、4和8N,形成孔道的TEWL初始值分别为12.9、33.0和40.4g·mv2·h-1;当长度分别为400、600和800μm,形成孔道的TEWL初始值分别为37.1、40.4和49.5 g·m2·h1;当针尖间距分别为400、600和800 μm,形成孔道的TEWL初始值分别为33.2、40.4和55.8 g·m-2.h-1;当基座面积分别为0.16、0.35和0.62 cm2,形成孔道的TEWL初始值分别为35.1、40.4和67.1 g·m-2·h-1,而圆锥形和铅笔形的微针产生的影响是近似的.铅笔形的可溶微针刺入皮肤,针尖间距分别为400、600和800 μm,形成孔道的TEWL初始值分别为49.8、60.5和70.5 g·m-2·h-1.不同性别和品系动物皮肤的TEWL基线值有所不同,但是孔道形成与闭合的趋势近似.微针引起的轻微红斑在24h内消退.不同参数微针对皮肤孔道产生的影响有一定差异,但孔道都可在24或48 h内闭合,皮肤局部刺激性轻微.

本文通过体外实验(溶出、透皮)、细胞毒性实验建立脂质创面敷料的安全性评价.建立基于电感耦合等离子体质谱(ICP-MS)和气相色谱质谱联用(GC-MS)测量溶出液、透皮液中新型脂质创面敷料残留物(三溴苯酚和铋)的分析方法.同时,使用四唑盐(MTT)比色法判断新型脂质创面敷料的材料毒性.结果表明,溶出液在2天、4天、7天内三溴苯酚的单位面积溶出量分别为(6.91±1.34)μg/cm2、(6.71±0.81)μg/cm2、(6.41±1.40)μg/cm2,铋的单位面积溶出量分别为(0.0086±0.0005)ng/cm2、(0.0097±0.0018)ng/cm2、(0.0556±0.0068)ng/cm2.透皮液在1天、2天内三溴苯酚的单位面积透过量分别为(0.16±0.01)μg/cm2、(1.11±0.01)μg/cm2,铋的单位面积透过量分别为(0.0036±0.0001)ng/cm2、(0.0117±0.0015)ng/cm2.细胞毒性实验结果证明本实验所用的脂质创面敷料对Hacat、HSF两种细胞毒性较小,等级为0或1.本实验所用新型脂质创面敷料的残留物在溶出液和透皮液中含量较低,细胞毒性等级较低,足以说明脂质创面敷料的安全性.

微针是一种新型的经皮药物递送技术,近年来可溶性微针作为其中的一类引起了研究者极大的关注.本研究通过文献及实验筛选优化可溶性聚合物微针的最适制备工艺;选择透明质酸(HA)、硫酸软骨素(CS)、聚乙烯吡咯烷酮(PVP)、聚乙烯醇(PVA)、羧甲基纤维素(CMC)、甲基乙烯基醚-马来酸酐共聚物(Gantrez)和羟丙基甲基纤维素(HPMC)这几种常见的高分子材料,分别以单一或复合的方式将高分子材料制备为载有模型药物盐酸利多卡因的可溶性聚合物微针.微针阴模模具通过金属微针倒模制得,可溶性微针通过阴模浇注制得.根据材料和药物的溶解性,以针型和气泡现象作为评判指标筛选出去离子水作为合适的微针制备溶剂.微针基质溶液中的气泡可以通过离心法快速、有效地去除.以外观形态、力学性能及吸湿性为评价指标,研究各个聚合物材料制备载药可溶性聚合物微针的可行性.调整优化处方中各个组分间的比例,以筛选出力学性能优良、不易吸湿且载有大剂量药物的聚合物材料;并对最优处方制备的可溶性微针进行表征及力学性能评价.结果表明,以Gan-trez S-97和HPMC这两种高分子材料复合制备的微针能载有70％的盐酸利多卡因,可顺利穿刺皮肤,力学性能优良且不易吸潮,可实现大剂量药物的顺利递送.

微针是一种高效、安全的新型经皮药物递送技术,具有其他传统经皮给药技术不具备的优势,而其皮肤穿刺性能是该技术能递送药物的前提和关键.笔者综述了目前现有穿刺性能的评价方法,从微针自身的机械强度以及皮肤穿刺效果出发,分别描述了断裂力测定、压变性能测试、有机染料染色法、表皮水分流失法、电阻抗法、组织学切片、共聚焦显微镜法以及光学相干断层扫描法等的应用,并且介绍了各种方法的适用范围与优缺点,为其他研究者在微针穿刺性能评价方法的选择上提供参考及借鉴.