Fabrication of Hybrid Coated Microneedles with Donepezil Utilizing Digital Light Processing and Semisolid Extrusion Printing for the Management of Alzheimer's Disease.

IF 4.5 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Molecular Pharmaceutics Pub Date : 2024-09-02 Epub Date: 2024-08-20 DOI:10.1021/acs.molpharmaceut.4c00377
Paraskevi-Kyriaki Monou, Eleftherios G Andriotis, Eirini Saropoulou, Emmanouil Tzimtzimis, Dimitrios Tzetzis, Georgios Komis, Chrysanthi Bekiari, Nikolaos Bouropoulos, Efterpi Demiri, Ioannis S Vizirianakis, Dimitrios G Fatouros
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Abstract

Microneedle (MN) patches are gaining increasing attention as a cost-effective technology for delivering drugs directly into the skin. In the present study, two different 3D printing processes were utilized to produce coated MNs, namely, digital light processing (DLP) and semisolid extrusion (SSE). Donepezil (DN), a cholinesterase inhibitor administered for the treatment of Alzheimer's disease, was incorporated into the coating material. Physiochemical characterization of the coated MNs confirmed the successful incorporation of donepezil as well as the stability and suitability of the materials for transdermal delivery. Optical microscopy and SEM studies validated the uniform weight distribution and precise dimensions of the MN arrays, while mechanical testing ensured the MNs' robustness, ensuring efficient skin penetration. In vitro studies were conducted to evaluate the produced transdermal patches, indicating their potential use in clinical treatment. Permeation studies revealed a significant increase in DN permeation compared to plain coating material, affirming the effectiveness of the MNs in enhancing transdermal drug delivery. Confocal laser scanning microscopy (CLSM) elucidated the distribution of the API, within skin layers, demonstrating sustained drug release and transcellular transport pathways. Finally, cell studies were also conducted on NIH3T3 fibroblasts to evaluate the biocompatibility and safety of the printed objects for transdermal applications.

Abstract Image

利用数字光处理和半固态挤压打印技术制造多奈哌齐混合涂层微针,用于治疗阿尔茨海默病
微针(MN)贴片作为一种直接向皮肤输送药物的经济有效的技术,正受到越来越多的关注。本研究采用了两种不同的三维打印工艺,即数字光处理(DLP)和半固态挤压(SSE),来生产涂层微针。涂层材料中加入了多奈哌齐(DN),这是一种用于治疗阿尔茨海默病的胆碱酯酶抑制剂。涂层 MN 的理化表征证实了多奈哌齐的成功加入以及材料的稳定性和透皮给药的适用性。光学显微镜和扫描电子显微镜研究验证了 MN 阵列均匀的重量分布和精确的尺寸,而机械测试则确保了 MN 的坚固性,从而保证了有效的皮肤渗透。体外研究对生产的透皮贴片进行了评估,显示了其在临床治疗中的潜在用途。渗透研究显示,与普通涂层材料相比,DN 的渗透率显著增加,这肯定了 MN 在增强透皮给药方面的有效性。共焦激光扫描显微镜(CLSM)阐明了原料药在皮肤层内的分布,证明了药物的持续释放和跨细胞转运途径。最后,还对 NIH3T3 成纤维细胞进行了细胞研究,以评估经皮应用的打印物体的生物相容性和安全性。
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来源期刊
Molecular Pharmaceutics
Molecular Pharmaceutics 医学-药学
CiteScore
8.00
自引率
6.10%
发文量
391
审稿时长
2 months
期刊介绍: Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.
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