Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus.
Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus.
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DOI：
10.1126/scitranslmed.3003453
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发表时间：
2012-06-13
影响因子：
17.1
通讯作者：
Hanes J
中科院分区：
文献类型：
--
作者：
Ensign LM;Tang BC;Wang YY;Tse TA;Hoen T;Cone R;Hanes J
覆盖不完全和作用持续时间短限制了阴道给药药物的有效性，包括预防性传播感染的杀菌剂。我们研究了纳米粒子的阴道分布、保留和安全性，这些纳米粒子的表面经过修饰以增强通过粘液的运输。我们发现，粘液穿透颗粒（MPP）在阴道上皮上提供均匀分布，而具有粘膜粘附性的传统纳米颗粒（CP）会被小鼠阴道粘液聚集，导致分布不良。此外，当低渗输送时，MPP 在几分钟内通过粘液平流（而不是扩散）输送到阴道皱襞（皱襞）深处。通过渗透到最深层的粘液层，6 小时后，与 CP 相比，更多的 MPP 保留在阴道中。 24小时后，当用传统的阴道凝胶递送时，模型药物的斑块保留在阴道上皮上，而上皮上涂有通过MPP递送的药物。然后我们开发了由单磷酸阿昔洛韦 (ACVp) 组成的 MPP。当在阴道单纯疱疹病毒 2 (HSV-2) 攻击之前施用时，ACVp-MPP 可以保护 53% 的小鼠，而可溶性药物只能保护 16% 的小鼠。总体而言，MPP 改善了阴道药物的分布和保留，比可溶性药物提供更有效的针对阴道病毒攻击的保护，并且每天给药一周时无毒。
Incomplete coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides for preventing sexually transmitted infections. We investigated vaginal distribution, retention, and safety of nanoparticles with surfaces modified to enhance transport through mucus. We show that mucus-penetrating particles (MPPs) provide uniform distribution over the vaginal epithelium, whereas conventional nanoparticles (CPs) that are mucoadhesive are aggregated by mouse vaginal mucus, leading to poor distribution. Moreover, when delivered hypotonically, MPPs were transported advectively (versus diffusively) through mucus deep into vaginal folds (rugae) within minutes. By penetrating into the deepest mucus layers, more MPPs were retained in the vaginal tract after 6 h compared to CPs. After 24 h, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPP. We then developed MPPs composed of acyclovir monophosphate (ACVp). When administered prior to vaginal herpes simplex virus 2 (HSV-2) challenge, ACVp-MPPs protected 53% of mice, compared to only 16% protected by soluble drug. Overall, MPPs improved vaginal drug distribution and retention, provided more effective protection against vaginal viral challenge than soluble drug, and were non-toxic when administered daily for one week.
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影响因子：
16.1
作者：
Lai, Samuel K.;Wang, Ying-Ying;Hanes, Justin
通讯作者：
Hanes, Justin
DOI：
10.2217/nnm.10.1
发表时间：
2010-02
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Mamo T;Moseman EA;Kolishetti N;Salvador-Morales C;Shi J;Kuritzkes DR;Langer R;von Andrian U;Farokhzad OC
通讯作者：
Farokhzad OC
影响因子：
2.9
作者：
Barnhart, KT;Pretorius, ES;Mauck, C
通讯作者：
Mauck, C
影响因子：
5.8
作者：
Chatterton, BE;Penglis, S;Hunt, B
通讯作者：
Hunt, B
影响因子：
1.6
作者：
Hubscher, CH;Brooks, DL;Johnson, JR
通讯作者：
Johnson, JR