# Innovative nanostructured lipid-particles of apocynin and clove oil tagged with Chitin oligosaccharide for amelioration of tacrolimus-induced nephrotoxicity

## TL;DR

This study develops a new oral delivery system using nanostructured particles to reduce kidney damage caused by the drug tacrolimus in transplant patients.

## Contribution

The novel contribution is the formulation of nanostructured lipid carriers combining apocynin, clove oil, and chitin oligosaccharide to mitigate tacrolimus-induced nephrotoxicity.

## Key findings

- The optimized formulation showed high encapsulation efficiency and stability for six months.
- Oral administration of the nanostructured particles improved kidney function in rat models of tacrolimus-induced injury.
- The system demonstrated a biphasic drug release profile and significant nephroprotective effects.

## Abstract

Tacrolimus (FK506) is a potent immunosuppressive agent widely employed to prevent allogeneic rejection in transplant recipients. However, its nephrotoxic effects pose significant limitations to long-term therapeutic use. To address this challenge, the present study aims to develop an innovative oral nano-delivery system designed to mitigate FK506-induced nephrotoxicity through the antioxidant properties of Apocynin (APO), clove oil (CO), and chitin oligosaccharide (CTOS). A nanostructured lipid carrier (NSLC) incorporating APO dissolved in CO and functionalized with CTOS was formulated using ultrasonic emulsification. Gelucire 43/01 and CO served as key lipid components in varying ratios. Physicochemical characterization of the developed NSLCs was conducted, assessing particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE%). The optimized formulation (F4) exhibited an EE% of 63.85 ± 1.98, PS of 123 ± 2.21 nm, PDI of 0.17 ± 0.09, and ZP of − 28 ± 1.98, demonstrating a biphasic release profile and stability under refrigerated conditions for six months. In vivo nephroprotective efficacy was evaluated in FK506-induced acute kidney injury (AKI) rat models, where oral administration of APO-loaded NSLCs significantly improved renal function and alleviated nephrotoxicity, as evidenced by biochemical markers and histopathological analyses. These findings underscore the potential of APO-loaded NSLCs as a promising oral phytopharmaceutical strategy for mitigating FK506-associated nephrotoxicity and enhancing therapeutic outcomes in transplant patients. Further studies are warranted to optimize and expand clinical applications.

The online version contains supplementary material available at 10.1038/s41598-025-13978-1.