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1.
The effect of microneedles on the skin permeability and antitumor activity of topical 5-fluorouracil
Topical 5-fluorouracil (5-FU) is approved for the treatment of superficial basal cell carcinoma and actinic keratosis. However, 5-FU suffers from poor skin permeation. Microneedles have been successfully applied to improve the skin permeability of small and large molecules, and even nanoparticles, by creating micron-sized pores in the stratum corneum layer of the skin. In this report, the feasibility of using microneedles to increase the skin permeability of 5-FU was tested. Using full thickness mouse skin mounted on Franz diffusion apparatus, it was shown that the flux of 5-FU through the skin was increased by up to 4.5-fold when the skin was pretreated with microneedles (500 μm in length, 50 μm in base diameter). In a mouse model with B16-F10 mouse melanoma cells implanted in the subcutaneous space, the antitumor activity of a commercially available 5-FU topical cream (5%) was significantly enhanced when the cream was applied on a skin area that was pretreated with microneedles, as compared to when the cream was simply applied on a skin area, underneath which the tumor cells were implanted, and without pretreatment of the skin with microneedles. Fluorouracil is not approved for melanoma therapy, but the clinical efficacy of topical 5-FU against tumors such as basal cell carcinoma may be improved by integrating microneedle technology into the therapy.KEY WORDS: Microneedles, 5-Fluorouracil, Cytotoxicity, Melanoma, Immunohistochemistry, Flux, Transdermal, Antitumor activity, Skin permeability 相似文献
2.
不锈钢微针经皮给药的研究 总被引:2,自引:0,他引:2
目的:将不锈钢微针阵列应用于经皮给药。考察离体大鼠皮肤经不同针形微针预处理相同时间、相同针形微针预处理不同时间后,模型药物鬼臼毒素经大鼠皮肤的透皮能力。方法:微针预处理大鼠皮肤后,用改进的Franz扩散池研究鬼臼毒素对皮肤的透皮速率。高效液相色谱法测定鬼臼毒素的含量。结果:皮肤经微针预处理后进行鬼臼毒素透皮,其透皮速率比未经微针处理时有明显提高。三角形微针、梯形微针、矛形微针对鬼臼毒素的促渗能力依次增强;三者所引起的鬼臼毒素在皮肤中的滞留量有显著差异。同种针形微针预处理皮肤时间越长,鬼臼毒素的透皮速率越大;但微针预处理时间对皮肤中的药物滞留量无显著影响。结论:微针用于药物经皮给药时,微针针形、微针的预处理时间对药物的经皮渗透具有重要影响。 相似文献
3.
《Expert opinion on drug delivery》2013,10(5):617-629
Importance of the field: The efficacy of microneedles in the area of transdermal drug delivery is well documented. Multiple studies have shown that enhancement of skin permeation by means of the creation of microscopic pores in the stratum corneum can greatly improve the delivery rates of drugs. However, skin pretreatment with microneedles is not the only factor affecting drug transport rates. Other factors, including drug formulation and rate of micropore closure, are also important for optimizing delivery by this route.Areas covered in this review: This review aims to highlight work that has been done in these areas, with an emphasis on drug formulation parameters that affect transdermal flux.What the reader will gain: This review creates an appreciation for the many factors affecting microneedle-enhanced delivery. Most results clearly indicate that microneedle skin pretreatment by itself may have different effects on drug transport depending on the formulation used, and formulation characteristics have different effects on the transport through untreated skin and microneedle-treated skin. Several formulation approaches are reported to optimize microneedle-enhanced drug delivery, including co-solvent use, vesicular, nanoparticulate and gel systems.Take home message: In addition to well-established factors that affect microneedle-assisted delivery (geometry, type of microneedle, etc.), formulation and pore viability are also critical factors that must be considered. 相似文献
4.
《Current medical research and opinion》2013,29(4):235-244
SummaryEflornithine HCl 13.9% cream (Vaniqa?) is a novel treatment for the management of unwanted facial hair in women. This paper reports the results of four modified open-label, within-subject vehicle-controlled studies evaluating the dermal safety of this topical treatment. In a repeated insult patch test (230 subjects), erythema with oedema occurred in 38.9% of subjects treated with eflornithine HCl 13.9% cream and 4.8% of subjects treated with vehicle cream. Challenge applications at previously untested sites following the three-week induction period produced noticeable erythema or greater on only four sites treated with eflornithine HCl 13.9% cream and one vehicletreated site. The erythema at these sites subsided substantially within 24 hours. In a three-week cumulative irritation study (30 subjects), the mean irritation score for sites treated with eflornithine HCl 13.9% cream was 1.33, compared with 0.76 at vehicletreated sites and 3.09 at positive-control (sodium lauryl sulphate-treated) sites (p < 0.001 between all three groups). In a phototoxicity study (25 subjects), irradiated sites showed either no reaction (40% of both sites treated with eflornithine HCl 13.9% cream and vehicle-treated sites), or mild erythema subsiding in all cases but one within 24 hours. No reaction was seen at non-irradiated sites. In a photocontact allergy study (30 subjects), challenge with eflornithine HCl 13.9% cream or its vehicle alone produced either no reaction or mild erythema subsiding within 24 hours at both irradiated and nonirradiated sites. No serious adverse events were reported during the studies, and the only adverse events considered related to treatment were pruritus (three subjects) and dry skin at test site (one subject). These results demonstrate that eflornithine HCl 13.9% cream does not have contact sensitising, photocontact allergic or phototoxic properties. It can cause irritation under exaggerated conditions of use. Eflornithine HCl 13.9% cream, therefore, has a favourable dermal safety profile appropriate for a topical treatment to be applied routinely. 相似文献
5.
Muhammad Sohail Arshad Saman Zafar Aleema Tehreem Zahra Mohammed Hussain Zaman Ambreen Akhtar Israfil Kucuk 《Journal of drug targeting》2021,29(1):60-68
Abstract The aim of this study was to develop heparin sodium loaded microneedle patches using different compositions of polyvinyl alcohol polymer and sorbitol. A vacuum micromolding technique was used to fabricate microneedle patches while heparin sodium was loaded into needle tips. Physical features of patches were evaluated by measuring thickness, width, folding endurance and swelling percentage. Patches were also characterised by optical microscopy and scanning electron microscopy to determine the microneedle length and surface morphologies. A preliminary assessment of the microneedle performance was studied by examining the in-vitro insertion to the parafilm and recording the in-vitro drug release profile. In-vivo activity of patches was confirmed by measuring activated partial thromboplastin time and histological examination of the micropierced skin tissues. Prepared patches were clear, smooth; uniform in appearance; with sharp pointed microprojections and remained intact after 1000 folding. The microneedles were stiffer in nature, as they reproduce microcavities in the parafilm membrane following hand pushing without any structural loss. Insertion study results showed successful insertion of microneedles into the parafilm. Disrupted stratum corneum evident from histological examination confirmed successful insertion of the microneedle without affecting the vasculature. In-vitro release study confirmed ~92% release of the loaded drug within 120?min. A significant prolongation of activated partial thromboplastin time (4 folds as compared to negative control) was recorded following the application of heparin sodium loaded microneedle patch onto rabbit skin. In conclusion microneedles are a valuable drug delivery system, benefiting the patients with minimal skin invasion and also allowing self-administration of heparin sodium in a sustained release manner for the management of chronic ailments. 相似文献
6.
目的 制备日夜两用生长激素微针贴片,模拟人体生理状态下内源性生长激素分泌的昼夜差异,实现生长激素给药时间和用量的优化,同时有效减轻皮下注射给药疼痛感,提高患者使用依从性。方法 采用铸模法制备微针贴片,通过光学显微镜和扫描电子显微镜观察微针表面形貌。经体外释放试验确定含生长激素微针制备的最佳工艺条件,包括优化紫外交联时间和交联剂含量。通过微针力学强度测试和体外透皮试验验证微针贴片有效穿透皮肤的可行性,通过圆二色光谱测定药物的稳定性。通过调试负载不同剂量生长激素制备日用和夜用微针贴片。结果 在显微镜下观察到微针排列整齐,针体完整、尖锐,微针在药物释放前后形貌无明显差异。工艺优化结果表明,当紫外交联时间为7 min,交联剂用量为1.5%时,微针贴片可以有效穿透离体大鼠皮肤,同时实现了生长激素在12 h内稳定释放,且微针释放出的蛋白药物构象无明显变化。通过在针体中负载不同剂量生长激素,制备了日用和夜用生长激素微针贴片。结论 本研究制备的微针能够顺应在生理状态下生长激素分泌的日夜差异,实现了适宜时间释放适量生长激素的目标,未来可进一步优化微针药物负载量以满足不同患者的实际使用需求,以期实现个体化治疗。 相似文献
7.
《Journal of drug targeting》2013,21(4):354-366
AbstractThe objective of this study was to investigate the effect of modulated current application using iontophoresis- and microneedle-mediated delivery on transdermal permeation of ropinirole hydrochloride. AdminPatch® microneedles and microchannels formed by them were characterized by scanning electron microscopy, dye staining and confocal microscopy. In vitro permeation studies were carried out using Franz diffusion cells, and skin extraction was used to quantify drug in underlying skin. Effect of microneedle pore density and ions in donor formulation was studied. Active enhancement techniques, continuous iontophoresis (74.13?±?2.20?µg/cm2) and microneedles (66.97?±?10.39?µg/cm2), significantly increased the permeation of drug with respect to passive delivery (8.25?±?2.41?µg/cm2). Modulated iontophoresis could control the amount of drug delivered at a given time point with the highest flux being 5.12?±?1.70?µg/cm2/h (5–7?h) and 5.99?±?0.81?µg/cm2/h (20–22?h). Combination of modulated iontophoresis and microneedles (46.50?±?6.46?µg/cm2) showed significantly higher delivery of ropinirole hydrochloride compared to modulated iontophoresis alone (84.91?±?9.21?µg/cm2). Modulated iontophoresis can help in maintaining precise control over ropinirole hydrochloride delivery for dose titration in Parkinson’s disease therapy and deliver therapeutic amounts over a suitable patch area and time. 相似文献
8.
《Expert opinion on pharmacotherapy》2013,14(2):177-183
Importance of the field: Hirsutism is the excess of terminal hairs in females and can result in immense distress. Women often spend significant time and funds seeking permanent hair removal. Commercially available physical therapies have usually already been accessed before presenting to the clinician for treatment.Areas covered in the review: We give a brief outline of physical therapies in the treatment of hirsutism with an emphasis on recently emerging hand-held laser hair removal devices for home use, which will become an increasingly important hair removal modality. The current evidence for topical ornithine decarboxylase inhibitor, oral antiandrogens, ovarian suppression and insulin sensitizers in the treatment of hirsutism is also reviewed.What the reader will gain: With advances in home laser hair removal systems the role of the clinician will increasingly become the use of pharmacotherapy in the treatment of resistant hirsutism. This article provides a review of the current literature for the use of pharmacotherapy.Take home message: Despite the availability of a range of physical and pharmacotherapies for the treatment of hirsutism, permanent hair removal remains elusive. 相似文献
9.
Abhishek Juluri Naresh Modepalli Seongbong Jo Michael A. Repka H. Nanjappa Shivakumar S. Narasimha Murthy 《Journal of pharmaceutical sciences》2013,102(3):987-993
Iron deficiency is one of the most prevalent and serious health issues among people all over the world. Iron–dextran (ID) colloidal solution is one among the very few US Food and Drug Administration (FDA)-approved iron sources for parenteral administration of iron. Parenteral route does not allow frequent administration because of its invasiveness and other associated complications. The main aim of this project was to investigate the plausibility of transdermal delivery of ID facilitated by microneedles, as an alternative to parenteral iron therapy. In vitro permeation studies were carried out using freshly excised hairless rat abdominal skin in a Franz diffusion apparatus. Iron repletion studies were carried out in hairless anemic rat model. The anemic rats were divided into intact skin (control), microneedle pretreated, and intraperitoneal (i.p.) groups depending on the mode of delivery of iron. The hematological parameters were measured intermittently during treatment. There was no improvement in the hematological parameters in case of control group, whereas, in case of microneedle pretreated and i.p. group, there was significant improvement within 2–3 weeks. The results suggest that microneedle-mediated delivery of ID could be developed as a potential treatment method for iron-deficiency anemia. 相似文献
10.
Guohua Li Advait Badkar Haripriya Kalluri Ajay K. Banga 《Journal of pharmaceutical sciences》2010,99(4):1931-1941
The objective of this study was to investigate the feasibility of using microneedle technology to enhance transcutaneous permeation of human immunoglobulin G (IgG) across hairless rat skin. Microchannels created by maltose and metal (DermaRoller?) microneedles were characterized by techniques such as methylene blue staining, histological examination, and calcein imaging. Methylene blue staining and histological sections of treated skin showed that maltose microneedles and DermaRoller? breached the skin barrier by creating microchannels in the skin with an average depth of ~150 µm, as imaged by confocal microscopy. Calcein imaging and pore permeability index values suggested the uniformity of the created pores in microneedle-treated skin. Transdermal studies with IgG indicated a flux rate of 45.96 ng/cm2/h, in vitro, and a Cmax of 7.27 ng/mL, in vivo, for maltose microneedles-treated skin while a flux rate of 353.17 ng/cm2/h, in vitro, and a Cmax of 9.33 ng/mL, in vivo, was achieved for DermaRoller?-treated skin. Transepidermal water loss measurements and methylene blue staining, in vivo, indicated the presence of microchannels for upto 24 h, when occluded. In conclusion, the microchannels created by maltose microneedles and DermaRoller? resulted in the percutaneous enhancement of a macromolecule, human IgG. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1931–1941, 2010 相似文献
11.
Context: Mercury is one of the skin-lightening ingredients in cosmetics as mercury ions are thought to inhibit the synthesis of the skin pigment melanin in melanocyte cells.Objective: The objective of this study was to evaluate the mercury levels of cosmetics currently marketed in Shijiazhuang, a northern city in China.Methods: We collected 146 random cosmetic samples and analyzed for mercury concentrations or levels by cold vapor atomic absorption spectrometry.Results: Among the 146 samples, 134 (91.8%) were positive for mercury, and the concentrations of mercury ranged from not detectable to 592?ng/g. Cosmetic samples for children and babies had the highest detection rate (100%), followed by shampoo and hair conditioner (92.3%) and skin-lightening cream (92.0%). All of them were lower than the acceptable limit (1?μg/g) in China.Discussion and conclusions: Cosmetics for skin had the highest mean mercury content (45?ng/g), followed by hair products (42.1?ng/g). The concentrations of mercury detected in samples were lower than the current legal limit in China, indicating it may not pose a risk to consumers. 相似文献
12.
目的:制备马钱子碱(Bru)双层聚合物可溶性微针,并考察其在不同载药方式下的体外经皮渗透特性。方法:以微针揭膜难易程度、阵列完整性、气泡量、针型、针尖硬度、背衬韧性等为考察指标分别筛选微针的针尖材料和背衬材料,并以微针形态为考察指标筛选基质溶胀方法和干燥方法,然后采用两步法制备双层聚合物可溶性微针,并进行表征和安全性评价。通过Franz扩散池法考察针尖载药、背衬载药、全载药Bru双层聚合物可溶性微针的体外经皮渗透特性,绘制体外透皮曲线并计算累积渗透量(Q)和累积渗透率。结果:优选的双层聚合物可溶性微针的制备工艺为以硫酸软骨素-聚乙烯吡咯烷酮K30(1∶1,m/m)作为针尖材料,15%聚乙烯醇作为背衬材料,在4℃冰箱静置1 h进行基质溶胀,干燥器室温干燥24 h。所制微针阵列完整,机械性能良好,能成功刺穿铝箔和大鼠皮肤,微针处理后皮肤在6 h内即可恢复到原来的状态。体外透皮试验结果显示,微针递药可大大提高Bru的经皮累积渗透量,针尖材料可在10 min内溶解并释放药物;针尖载药微针在8 h内基本释放完全,Q8 h为102.185μg/cm2,累... 相似文献
13.
Purpose: A topical microemulsion (ME)-based hydrogel was developed to enhance permeation of an antifungal drug, sertaconazole (STZL) for effective eradication of cutaneous fungal infection.Methods: Pseudo-ternary phase diagrams were used to determine the existence of MEs region. ME formulations were prepared with oleic acid, Tween 80, propylene glycol (PG) and water. Carbopol 940 (0.75% w/w) was used for preparation of hydrogel of STZL microemulsion (HSM) and characterized. The in vitro and in vivo evaluation of prepared HSM and commercial cream of STZL were compared.Results: The viscosity, average droplet size and pH of HSM were 154.23?±?0.54 to 162.52?±?0.21?Pas, 42.3–91.7?nm and 6.9–7.2?, respectively. Permeation rate of STZL from optimized formulation (HSM-4), composed with oleic acid (8.75 % w/w), Tween 80 (33.35% w/w), PG (33.35% w/w) and water (24.55% w/w) was observed higher in compare with other HSMs and commercial cream. HSM-4 was stable, three times higher drug retention capacity in skin than commercial cream and did not caused any erythema or edema based on skin sensitivity study on rabbit. The average zone of inhibition of HSM-4 (23.54?±?0.72?mm) was higher in compare with commercial cream (16.53?±?0.63?mm) against Candida albicans.Conclusion: The results of study showed that ME played a major role in permeation enhancing and skin retention effect of HSM and the concentration of STZL used for cutaneous fungal infection could be decreased by using ME based hydrogel preparation. 相似文献
14.
Polymer Microneedles for Controlled-Release Drug Delivery 总被引:5,自引:0,他引:5
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. 相似文献
15.
《Expert opinion on drug delivery》2013,10(9):1095-1108
Importance of the field: In recent years there has been increasing awareness that the hair follicles and their associated pilosebaceous structures may act as significant permeation pathways and/or reservoirs for topically applied drugs. This has implications in terms of dermatological therapy for acne, hirsutism, alopecias or certain skin cancers as well as systemic drug delivery. As the processes modulating follicular drug penetration are poorly understood at present, there is an emergent need for methodologies that can quantify follicular drug penetration and deposition. So far, a review article specifically dedicated to these methodological aspects has not yet been written.Areas covered in this review: This paper reviews the available quantitative follicular methodologies that have been developed over the years, describing the advantages and disadvantages of each approach. This review covers comparative techniques that are based on measuring drug flux through ‘follicle-free’ and ‘follicle-containing’ integuments, the skin sandwich, differential stripping and optical imaging-based technologies. Techniques for measuring drug–sebum interactions are also discussed.What the reader will gain: The reader will develop an understanding of the complexities involved in quantifying drug delivery through follicles and pilosebaceous units. The Expert opinion section will give the reader insights into how more broad-ranging future research could allow identification of the most useful methods for quantifying follicular drug transport.Take home message: This is still a poorly understood field. It clearly warrants much larger scale studies than have been performed so far involving multiple techniques and multiple drugs. 相似文献
16.
Leonard Y. Chu Seong-O. Choi Mark R. Prausnitz 《Journal of pharmaceutical sciences》2010,99(10):4228-4238
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. 相似文献
17.
18.
Ryan F. Donnelly Rita Majithiya Thakur Raghu Raj Singh Desmond I. J. Morrow Martin J. Garland Yusuf K. Demir Katarzyna Migalska Elizabeth Ryan David Gillen Christopher J. Scott A. David Woolfson 《Pharmaceutical research》2011,28(1):41-57
Purpose
Design and evaluation of a novel laser-based method for micromoulding of microneedle arrays from polymeric materials under ambient conditions. The aim of this study was to optimise polymeric composition and assess the performance of microneedle devices that possess different geometries.Methods
A range of microneedle geometries was engineered into silicone micromoulds, and their physicochemical features were subsequently characterised.Results
Microneedles micromoulded from 20% w/w aqueous blends of the mucoadhesive copolymer Gantrez® AN-139 were surprisingly found to possess superior physical strength than those produced from commonly used pharma polymers. Gantrez® AN-139 microneedles, 600 ??m and 900 ??m in height, penetrated neonatal porcine skin with low application forces (>0.03 N per microneedle). When theophylline was loaded into 600 ??m microneedles, 83% of the incorporated drug was delivered across neonatal porcine skin over 24 h. Optical coherence tomography (OCT) showed that drug-free 600 ??m Gantrez® AN-139 microneedles punctured the stratum corneum barrier of human skin in vivo and extended approximately 460 µm into the skin. However, the entirety of the microneedle lengths was not inserted.Conclusion
In this study, we have shown that a novel laser engineering method can be used in micromoulding of polymeric microneedle arrays. We are currently carrying out an extensive OCT-informed study investigating the influence of microneedle array geometry on skin penetration depth, with a view to enhanced transdermal drug delivery from optimised laser-engineered Gantrez® AN-139 microneedles. 相似文献19.
《Expert opinion on drug delivery》2013,10(4):513-533
Importance of the field: Microneedles are small-scale devices that are finding use for transdermal delivery of protein-based pharmacologic agents and nucleic acid-based pharmacologic agents; however, microneedles prepared using conventional microelectronics-based technologies have several shortcomings, which have limited translation of these devices into widespread clinical use.Areas covered in this review: Two-photon polymerization is a laser-based rapid prototyping technique that has been used recently for direct fabrication of hollow microneedles with a wide variety of geometries. In addition, an indirect rapid prototyping method that involves two-photon polymerization and polydimethyl siloxane micromolding has been used for fabrication of solid microneedles with exceptional mechanical properties.What the reader will gain: In this review, the use of two-photon polymerization for fabricating in-plane and out-of-plane hollow microneedle arrays is described. The use of two-photon polymerization-micromolding for fabrication of solid microneedles is also reviewed. In addition, fabrication of microneedles with antimicrobial properties is discussed; antimicrobial microneedles may reduce the risk of infection associated with the formation of channels through the stratum corneum.Take home message: It is anticipated that the use of two-photon polymerization as well as two-photon polymerization-micromolding for fabrication of microneedles and other microstructured drug delivery devices will increase over the coming years. 相似文献
20.
To reduce the effort required to penetrate the skin and optimize drug release profiles, bioceramic microneedle arrays with higher-aspect-ratio needles and a flexible and self-swelling substrate have been developed. Swelling of the substrate can assist in separating it from the needles and leave them in the skin as a drug depot. The preparation procedures for this bioceramic microneedle are described in the paper. Clonidine hydrochloride, the model drug, was released in a controlled manner by the microneedle device in vitro. Results showed that the microneedle array with a flexible and self-swelling substrate released the drug content faster than the array with a rigid substrate. Disintegration of the needle material and diffusion of the drug molecules are believed as the main control mechanisms of the drug release from these microneedle arrays. Ex vivo skin penetration showed that they can effectively penetrate the stratum corneum without an extra device. This work represents a progression in the improvement of bioceramic microneedles for transdermal drug delivery. 相似文献