Fabrication and Characterization of Dissolvable Microneedle Arrays for Effective

可溶性微针阵列的制备和表征，以实现有效的

• 批准号: 8533780
• 负责人: Louis D Falo
• 金额: $ 37.3万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8533780
• 关键词: Address; Adjuvant; Antigens; Biology; Characteristics; Clinical; Clinical Trials; Complex; Coupled; Cutaneous; Data; Dermatology; Dermis; Development; Devices; Drug Delivery Systems; Economics; Effectiveness; Encapsulated; Engineering; Epidermis; Failure; Goals; Human; Immunization; Immunization Programs; In Vitro; Knowledge; Laboratories; Lead; Life; Mechanics; Mediating; Methods; Modeling; Molds; Needles; Oral; Patients; Penetration; Positioning Attribute; Prevention; Process; Property; Publishing; Reproducibility; Research Design; Research Personnel; Skin; Speed; Stretching; Techniques; Technology; Temperature; Testing; Therapeutic Agents; Time; Translations; Vaccines; Variant; base; clinically relevant; design; experience; human disease; immunogenicity; in vivo; novel; prevent; public health relevance; therapeutic vaccine; viscoelasticity

DESCRIPTION (provided by applicant): Transdermal delivery of biologics using microneedle-array (MNA) based devices offers attractive theoretical advantages over prevailing oral and needle-based drug delivery methods. However, considerable practical limitations in design, fabrication, and testing are preventing the discovery of clinically relevant array designs. The goal of this project is to rationally design a cutaneous delivery platform based on a dissolvable microneedle array that enables efficient, precise, and reproducible delivery of biologically active molecules to human skin. Importantly, we propose to accomplish this with a microneedle array delivery platform that is directly applicable to patient-friendly, clinical delivery of a broad range of therapeutic agents. We have assembled a multi-disciplinary team of investigators with broad and directly relevant experience in mechanical engineering, cutaneous biology, and dermatology. Together we have developed novel and comprehensive micro-milling based fabrication technologies that uniquely position us to accomplish this goal. Through studies proposed here, we will identify geometric and mechanical properties of microneedle and array configurations that impact the effectiveness and reproducibility of MNA drug delivery. This new knowledge will be applied to the design and fabrication of MNAs with physical characteristics compatible with effective intracutaneous drug delivery. PUBLIC HEALTH RELEVANCE: Transdermal delivery of biologics using microneedle-array (MNA) based devices offers attractive theoretical advantages over prevailing oral and needle-based drug delivery methods. However, considerable practical limitations in design, fabrication, and testing are preventing the discovery of clinically relevant array designs. The goal of this project is to rationally design a cutaneous delivery platform based on a dissolvable microneedle array that enables efficient, precise, and reproducible delivery of biologically active molecules to human skin. Importantly, we propose to accomplish this with a microneedle array delivery platform that is directly applicable to patient-friendly, clinical delivery of a broad range of therapeutic agents.

描述（由申请人提供）：使用基于微针阵列（MNA）的装置进行生物制剂的透皮给药，与流行的口服和基于针的药物给药方法相比，具有吸引人的理论优势。然而，在设计、制造和测试方面的相当大的实际限制阻碍了临床相关阵列设计的发现。该项目的目标是合理设计一种基于可溶解微针阵列的皮肤递送平台，该平台能够将生物活性分子高效、精确和可重复地递送到人体皮肤。重要的是，我们建议用微针阵列递送平台来实现这一点，该微针阵列递送平台直接适用于广泛范围的治疗剂的患者友好的临床递送。我们组建了一支多学科的研究团队，在机械工程、皮肤生物学和皮肤病学方面具有广泛而直接的相关经验。我们共同开发了新颖而全面的基于微铣削的制造技术，使我们能够实现这一目标。通过这里提出的研究，我们将确定影响MNA药物递送的有效性和再现性的微针和阵列配置的几何和机械特性。这一新的知识将被应用到设计和制造的MNAs的物理特性兼容有效的皮内给药。 公共卫生关系：使用基于微针阵列（MNA）的装置的生物制剂的经皮递送提供了优于流行的口服和基于针的药物递送方法的有吸引力的理论优势。然而，在设计、制造和测试方面的相当大的实际限制阻碍了临床相关阵列设计的发现。该项目的目标是合理设计一种基于可溶解微针阵列的皮肤递送平台，该平台能够将生物活性分子高效、精确和可重复地递送到人体皮肤。重要的是，我们建议用微针阵列递送平台来实现这一点，该微针阵列递送平台直接适用于广泛范围的治疗剂的患者友好的临床递送。

项目成果

Dissolvable microneedle arrays for intradermal delivery of biologics: fabrication and application.

• DOI: 10.1007/s11095-013-1137-x
• 发表时间: 2014-01
• 期刊: PHARMACEUTICAL RESEARCH
• 影响因子: 3.7
• 作者: Bediz, Bekir;Korkmaz, Emrullah;Khilwani, Rakesh;Donahue, Cara;Erdos, Geza;Falo, Louis D., Jr.;Ozdoganlar, O. Burak
• 通讯作者: Ozdoganlar, O. Burak

Therapeutic intradermal delivery of tumor necrosis factor-alpha antibodies using tip-loaded dissolvable microneedle arrays.

• DOI: 10.1016/j.actbio.2015.05.036
• 发表时间: 2015-09
• 期刊: Acta biomaterialia
• 影响因子: 9.7
• 作者: Korkmaz E;Friedrich EE;Ramadan MH;Erdos G;Mathers AR;Burak Ozdoganlar O;Washburn NR;Falo LD Jr
• 通讯作者: Falo LD Jr