Enhanced Bioavailability by Orally Administered Sirolimus Nanocrystals

Abstract

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.

The role of nanotechnology in current COVID-19 outbreak

“…However, the patients are more compatible with the oral administration of the injection [ 56 ]. Some other nanoplatforms that have been applied to produce interferon are a derivate of chitosan NPs [ 25 , 56 , 59 , 83 ], Fe3O4 NPs [ 84 ], Disulfide-based PEGylatednanogels [ 85 ], CD44-targeted glutathione-sensitive hyaluronic acid-mercaptopurine prodrug (HA-GS-MP) [ 86 ],Nanoliposomes [ 87 ], Sirolimus nanocomposites [ 88 ], Sirolimus Nanocrystals [ 89 ] and Calcium phosphate (CaP) NP-based vaccine carrier functionalized with CpG and viral peptides [ 90 ]. These NPs can encapsulate biomaterials and drugs that induce interferon-α.…”

Drug delivery systems as immunomodulators for therapy of infectious disease: Relevance to COVID-19

“…Rapamycin is poorly soluble, undergoes extensive first pass metabolism and its bioavailability can be altered by diet [92] . Nanoformulations of rapamycin have been designed for a number of treatments, including but not limited to: immune suppression in transplant patients, lymphangioleiomyomatosis and age-related diseases including cancer and may have applications in COVID-19 [93] , [94] , [95] , [96] .…”