Efficiency encapsulation of FK506 with new dual self-assembly multi-hydrophobic-core nanoparticles for preventing keratoplasty rejection.

Nanoparticles self-assembled by amphiphilic co-polymers for loading hydrophobic molecules have been intensively investigated. However, their hydrophobic molecule-loading capacity is low due to the limitation of hydrophobic groups in these co-polymers. In this regard, new lysine oligomer-based multi-hydrophobic side chain polymers (MHCPs) w ere synthesized by polymerization of γ-benzyl-L glutamate N-carboxy anhydride initiated by side-chain primary amino groups in lysine oligomer. Each hydrophobic side chain in MHCPs could be self-assembled by hydrophobic interaction to form multi-hydrophobic-core nanoparticles (MHC-NPs) with silkworm cocoon-, grape cluster-, and butterfly-like shapes (depending on hydrophobic-side-chains lengths). To increase their stability, MHC-NPs w ere dually self-assembled with polyethylene glycol-polyglutamic acid through charge interaction. Each hydrophobic core in MHC-NPs served as a carrier for hydrophobic molecules, endowing their nano-structure with high loading capacity. MHC-NPs w ere employed to load FK506, and the loading amount w as 18% and the loading efficiency w as 80%, which are higher than those of previously reported nano-micelles self-assembled by linear amphiphilic co-polymers. Topical administration of FK506-loaded nanoparticle (FK506-NP) could significantly prolong retention of FK506 on the eye surface. FK506-NP exhibited higher in vivo immunosuppressive effects than free FK506 and commercial FK506 eye drop, as well as a better protective effect against immunotoxicity in the corneal grafts after keratoplasty. This article is protected by copyright. All rights reserved.