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. 2025 Aug 8;15(1):29011.
doi: 10.1038/s41598-025-13978-1.

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

Amir Elsayed Maghrabia  1   2 , Mariza Fouad Boughdady  3 , Sherry Mohamed Khater  4 , Irhan Ibrahim Abu Hashim  3 , Mahasen Mohammed Meshali  3
Affiliations

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

Amir Elsayed Maghrabia et al. Sci Rep. .

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.

Keywords: Apocynin; Clove oil; Nanostructured lipid carrier; Nephrotoxicity; Phytopharmaceuticals; Targeted.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The study protocol was reviewed and accepted by the ethical committee of the Faculty of Pharmacy, Mansoura University, Mansoura, Egypt, following the “Principles of Laboratory Animal Care, National Materials Institute of Health Publication (No. 85 − 23, revised 1985)” (Ethical Approval Code 2024 − 163).

Figures

Fig. 1
Fig. 1
FT-IR spectra of (a) APO, (b) CO, (c) GE, (d) CTOS, (e) physical mixture, (f) plain optimal formula, and (g) optimal formula (F4).
Fig. 2
Fig. 2
DSC spectra of (a) APO, (b) CO, (c) GE, (d) CTOS, (e) physical mixture, (f) plain optimal formula, and (g) optimal formula (F4).
Fig. 3
Fig. 3
XRD diffractograms of (a) APO, (b) CO, (c) GE, (d) CTOS, (e) physical mixture, (f) plain optimal formula, and (g) optimal formula (F4).
Fig. 4
Fig. 4
TEM images of APO-loaded NSLC optimal formula (F4).
Fig. 5
Fig. 5
SEM images of the APO-loaded NSLCs optimal formula (F4).
Fig. 6
Fig. 6
The in vitro release pattern of APO from aqueous solution in comparison with the optimal formula (F4) at three different pH media: (a) pH 1.2, (b) pH 6.8, and (c) pH 7.4. Each point represents the mean ± SD (n = 3).
Fig. 7
Fig. 7
Effect of APO on FK506-induced histopathological changes in kidneys of different experimental groups: (a) Normal control group; (b) Positive control group; (c) Pure APO group, and (d) APO-NSLCs (F4). (n = 6 per group, Low magnification X:100, bar:100 μm).
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