Enhanced Bioavailability by Orally Administered Sirolimus Nanocrystals

Jianglong Kong, Kai Wu, Ying Ji, Kui Chen, Jiaxin Zhang, Hui Sun, Yuelan Liang, Wei Liang, Yanan Chang, Jenny Cheng, Junmao Tong, Juan Li, Gengmei Xing, Guogang Chen

Research output: Journal article publicationJournal articleAcademic researchpeer-review

4 Citations (Scopus)


Nanocrystallization can improve the dissolvability of insoluble medicines in water, making them easier to administer. In the present study, sirolimus (SRL) was nanocrystallized, and the transport mechanism and efficacy of both formulations were compared in vitro and in vivo. The results showed that the 120 nm sirolimus nanocrystals (SRL NCs) had better ability to pass through the Caco-2 cell monolayer. SRL NCs were uptaken by Caco-2 cells via multiple endocytosis pathways, and the endoplasmic reticulum (ER), Golgi apparatus, and microtubules were identified as vital organelles for expelling SRL NCs out of the cells. SRL NCs decreased CD4+/CD8+ in normal mice after 14 days of daily gavage administration. Furthermore, SRL NCs enhanced the immune tolerance in an ovalbumin (OVA)-sensitized mouse model. SRL NCs significantly increased the percentage of Tregs (CD25+Foxp3+) among CD4+T cells. Collectively, these findings demonstrate that nanocrystallization of SRL enhances oral bioavailability, transcytosis, and prolongs drug residence time in vivo, while also enhancing SRL efficacy.

Original languageEnglish
Pages (from-to)4612-4621
Number of pages10
JournalACS Applied Bio Materials
Issue number10
Publication statusPublished - 21 Oct 2019
Externally publishedYes


  • bioavailability
  • immune tolerance
  • oral administration
  • sirolimus nanocrystals
  • transport mechanisms

ASJC Scopus subject areas

  • General Chemistry
  • Biomaterials
  • Biomedical Engineering
  • Biochemistry, medical


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