Pharmacokinetic behaviors of intravenously administered siRNA in glandular tissues

46Citations
Citations of this article
67Readers
Mendeley users who have this article in their library.

Abstract

The pharmacokinetics of small interfering RNAs (siRNAs) is a pivotal issue for siRNA-based drug development. In this study, we comprehensively investigated the behavior of siRNAs in vivo in various tissues and demonstrated that intravenously-injected naked siRNA accumulated remarkably in the submandibular gland, bulbourethral gland, and pancreas, with a respective half-life of ~22.7, ~45.6, and ~30.3 h. This was further confirmed by gel separation of tissue homogenates and/or supernatants. In vivo imaging and cryosectioning suggested that delivery carriers significantly influence the distribution and elimination profiles of siRNA. Gene-silencing assays revealed that neither naked nor liposome-formulated siRNA resulted in gene knockdown in the submandibular and bulbourethral glands after systemic administration, suggesting that these glands function as drug reservoirs that enable slow siRNA release into the circulation. But robust gene-silencing was achieved by local injection of liposome-encapsulated siRNA into the submandibular gland. Our results enhance understanding of the pharmacokinetic properties of siRNAs and we believe that they will facilitate the development of siRNA therapy, especially for the submandibular gland.

References Powered by Scopus

Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles

2247Citations
N/AReaders
Get full text

Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs

1064Citations
N/AReaders
Get full text

RNAi therapeutics: A potential new class of pharmaceutical drugs

1000Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Therapeutic siRNA: state of the art

985Citations
N/AReaders
Get full text

Membrane-destabilizing ionizable lipid empowered imaging-guided siRNA delivery and cancer treatment

137Citations
N/AReaders
Get full text

Clinical advances of siRNA therapeutics

135Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Huang, Y., Cheng, Q., Ji, J. L., Zheng, S., Du, L., Meng, L., … Liang, Z. (2016). Pharmacokinetic behaviors of intravenously administered siRNA in glandular tissues. Theranostics, 6(10), 1528–1541. https://doi.org/10.7150/thno.15246

Readers over time

‘16‘17‘18‘19‘20‘21‘22‘23‘2405101520

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 26

79%

Professor / Associate Prof. 4

12%

Lecturer / Post doc 2

6%

Researcher 1

3%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 12

40%

Medicine and Dentistry 7

23%

Agricultural and Biological Sciences 6

20%

Pharmacology, Toxicology and Pharmaceut... 5

17%

Article Metrics

Tooltip
Social Media
Shares, Likes & Comments: 16

Save time finding and organizing research with Mendeley

Sign up for free
0