Glycol chitosan-based renal docking biopolymeric nanomicelles for site-specific delivery of the immunosuppressant.

• Hydrophobically modified glycol chitosan polymeric nanomicelles (HGC) loaded with hydrophobic drug tacrolimus (TAC). • Selective deposition of TAC into the kidney because of the in-built property of glycol chitosan to target the kidney. • Megalin receptor-mediated endocytosis is involved in the uptake and retention of HGC-TAC nanomicelles in the kidney. • Demonstrates the potential of HGC nanomicelles as a novel strategy to deliver drugs specifically to kidneys without any systemic toxicity. In this study, we propose the use of glycol chitosan for the targeted delivery of hydrophobic drugs such as tacrolimus (TAC) towards the kidney. We synthesized a hydrophobically modified glycol chitosan (HGC) polymeric nanomicelle followed by loading TAC resulting in TAC loaded HGC nanomicelles (HGC-TAC). The HGC-TAC nanomicelles displayed spherical morphology with superior drug loading content and encapsulation efficiency. in vitro and in vivo evaluations demonstrated that HGC-TAC nanomicelles are non toxic and delivered TAC preferentially to kidney while lowering the plasma concentrations. The therapeutic effects of HGC-TAC and unencapsulated ("bare") TAC on the kidneys showed that a single intravenous administration of HGC-TAC achieved a therapeutic efficacy comparable to that obtained from daily intraperitoneal injections of TAC for 14 days without any systemic side effects. Thus, HGC-TAC nanomicelles could be effectively used for delivery of TAC towards the kidney, highlighting its potential as a safe modality for renal-targeted delivery of therapeutics. [ABSTRACT FROM AUTHOR]