Title : Ectopic high endothelial venule-targeted nano delivery for type 1 diabetes
Abstract:
Targeted drug delivery systems hold the remarkable potential to improve the therapeutic index of diabetes medications. Herein, we developed a targeted delivery platform for type 1 diabetes (T1D) treatment using high endothelial venule (HEV)-targeted nanoparticles. We encapsulated anti-CD3 in PLGA nanoparticles (NPs) and conjugated mAb on the surface of NPs. Our mAb-NP localized to pancreatic lymph nodes (PLNs) and pancreata in NOD mice and encapsulation of anti-CD3 in MECA79-NP enhanced its delivery to these organs. Treatment of hyperglycermic NOD mouse model with mAb-anti-CD3-NP resulted in significant reversal of T1D, as compared to non-treatment, empty NP, and free anti-CD3. mAb-anti-CD3-NP treatment caused a marked increase of regulatory T (Treg) cells in pancreata. Our data suggested that ectopic HEV expressed in pancreata of T1D patients. Our study demonstrates that HEV-targeting nanovehicles constitute a novel drug delivery platform that can augment the effects of immunosuprression as well as reduce the inflammatory risk in treating T1D. Moreover, HEV-targeting therapeutics may be used as means by which drugs are delivered specifically to PLNs and pancreata, thereby prolonging the reversal of T1D patients.
