Stimuli-sensitive thiolated hyaluronic acid based nanofibers: synthesis, preclinical safety and in vitro anti-HIV activity

被引：32

作者：

Agrahari, Vivek ^{[1
]}

Meng, Jianing ^{[1
]}

Ezoulin, Miezan J. M. ^{[1
]}

Youm, Ibrahima ^{[1
,2
]}

Dim, Daniel C. ^{[3
]}

Molteni, Agostino ^{[3
]}

Hung, Wei-Ting ^{[4
]}

Christenson, Lane K. ^{[4
]}

Youan, Bi-Botti C. ^{[1
]}

机构：

[1] Univ Missouri, Sch Pharm, Div Pharmaceut Sci, Lab Future Nanomed & Theoret Chronopharmaceut, Kansas City, MO 64108 USA

[2] Hough Ear Inst, Oklahoma City, OK 73112 USA

[3] Univ Missouri, Sch Med, Kansas City, MO 64108 USA

[4] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA

来源：

NANOMEDICINE | 2016年 / 11卷 / 22期

关键词：

anti-HIV activity; electrospinning; HIV vaginal transmission; nanofibers; preclinical safety; tenofovir; thiolated hyaluronic acid; topical microbicide; vaginal delivery; NANOPARTICLE TRACKING ANALYSIS; DRUG-DELIVERY; BIOMEDICAL APPLICATIONS; CHITOSAN NANOPARTICLES; SEXUAL TRANSMISSION; VAGINAL DELIVERY; HUMAN SEMEN; ELECTROSPUN; PREVENTION; MICROBICIDE;

D O I：

10.2217/nnm-2016-0103

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Aim: To develop a seminal enzyme bioresponsive, mucoadhesive nanofibers (NFs) as safe and effective nanocarriers for the prevention of HIV vaginal transmission. Methods: A novel thiolated hyaluronic acid (HA-SH) polymer was synthesized to fabricate tenofovir (TFV)-loaded electrospun NFs (HA-SH-NFs) and characterized in vitro/in vivo. Results: A triggered drug release (87% w/w) from the engineered HA-SH-NFs (mean diameter similar to 75 nm) occured within 1 h under the influence of seminal hyaluronidase enzyme. HA-SH-NFs were noncytotoxic, induced no damage on the C57BL/6 mice genital-tract and other organs. No significant CD45 cell-infiltration and changes in cytokines level in cervicovaginal tissues were observed. HA-SH-NFs significantly enhanced both TFV retention and bioavailability in vaginal tissue compared with the 1% TFV-gel. The anti-HIV activity of TFV (on pseudotyped virus followed by luciferase assay) was not adversely affected by the electrospinning process. Conclusion: HA-SH-NFs developed in this study could potentially serve as a safe nanotemplate for topical intravaginal delivery of HIV/AIDS microbicides.

引用

页码：2935 / 2958

页数：24

共 95 条

[1]

HYALURONIDASE ACTIVITY IN HUMAN SEMEN - CORRELATION WITH FERTILIZATION IN-VITRO [J].