Therapeutic intradermal delivery of tumor necrosis factor-alpha antibodies using tip-loaded dissolvable microneedle arrays.
Therapeutic intradermal delivery of tumor necrosis factor-alpha antibodies using tip-loaded dissolvable microneedle arrays.
复制标题
DOI：
10.1016/j.actbio.2015.05.036
复制
发表时间：
2015-09
影响因子：
9.7
通讯作者：
Falo LD Jr
中科院分区：
文献类型：
--
作者：
Korkmaz E;Friedrich EE;Ramadan MH;Erdos G;Mathers AR;Burak Ozdoganlar O;Washburn NR;Falo LD Jr
肿瘤坏死因子-α（TNF-α）特异性抗体（anti-TNF-α Ab）已被证明是有效的TNF抑制剂和一系列炎性疾病的有效治疗剂。通常，这些药物全身给药，但足以在外周组织中达到局部有效浓度的全身给药与全身免疫抑制和相关不良事件相关。在这里，我们评估了使用尖端加载的可溶性微针阵列（MNAs）局部皮内递送抗TNF-α Ab。使用微磨/旋转浇铸制造方法由羧甲基纤维素（CMC）产生具有方尖碑形状微针的MNA，所述微针在针尖中掺入抗体货物。我们发现，使用这种室温制造工艺整合到MNAs中的抗TNF-α Ab保持了构象依赖的TNF-α结合活性。此外，这些MNA有效地将抗TNF-α抗体递送至人皮肤的真皮，具有临床适用的释放曲线。为了评价MNA递送的抗TNF-α Ab的功能，我们将含有抗TNF-α Ab的MNA应用于小鼠皮肤上建立的银屑病样病变。MNA抗TNF-α Ab治疗降低了银屑病样炎症的关键生物标志物，包括表皮厚度和IL-1β表达。总之，这些结果证明了MNA将抗TNF-α Ab有效且生物学有效地递送至小鼠和人皮肤的皮内微环境，并支持开发用于临床应用的MNA介导的抗体递送。
Tumor necrosis factor-alpha (TNF-α) specific antibodies (anti-TNF-α Ab) have been shown to be potent TNF inhibitors and effective therapeutics for a range of inflammatory diseases. Typically, these drugs are administered systemically, but systemic dosing sufficient to achieve locally effective concentrations in peripheral tissues has been associated with systemic immunosuppression and related adverse events. Here, we evaluated the use of tip-loaded dissolvable microneedle arrays (MNAs) for localized intradermal delivery of anti-TNF-α Ab. MNAs with obelisk shape microneedles that incorporate the antibody cargo in the needle tips were created from carboxymethylcellulose (CMC) using a micromilling/spin-casting fabrication method. We found that Anti-TNF-α Ab integrated into MNAs using this room temperature fabrication process maintained conformationally dependent TNF-α binding activity. Further, these MNAs efficiently delivered anti-TNF-α antibodies to the dermis of human skin with clinically applicable release profiles. To evaluate MNA delivered anti-TNF-α Ab function, we applied anti-TNF-α Ab containing MNAs to established psoriasiform lesions on the skin of mice. MNA anti-TNF-α Ab treatment reduced key biomarkers of psoriasiform inflammation including epidermal thickness and IL-1β expression. Taken together, these results demonstrate efficient and biologically effective MNA delivery of anti-TNF-α Ab to the intradermal microenvironment of the skin in mice and humans, and support the development of MNA mediated antibody delivery for clinical applications.
登录
查看更多内容
DOI：
10.1016/j.ejpb.2013.10.001
发表时间：
2014-02-01
影响因子：
4.9
作者：
Liu, Shu;Jin, Mei-na;Yamamoto, Akira
通讯作者：
Yamamoto, Akira
影响因子：
4.9
作者：
Gottlieb, AB;Antoni, CE
通讯作者：
Antoni, CE
影响因子：
4.4
作者：
Mathers, Alicia R.;Janelsins, Brian M.;Larregina, Adriana T.
通讯作者：
Larregina, Adriana T.
DOI：
10.1007/b137240
发表时间：
2006-01-01
期刊：
TISSUE ENGINEERING I: SCAFFOLD SYSTEMS FOR TISSUE ENGINEERING
影响因子：
--
作者：
Nair, Lakshmi S.;Laurencin, Cato T.
通讯作者：
Laurencin, Cato T.
影响因子：
2.9
作者：
RANADE, VV
通讯作者：
RANADE, VV