Chitosan-encapsulated Aloe vera nanoparticles outperform carrier-free forms in enhancing MSCs therapy for amikacin nephrotoxicity.

Acute kidney injury (AKI) induced by nephrotoxic drugs like amikacin remains a clinical challenge, with mesenchymal stem cells (MSCs) showing limited efficacy due to poor survival and engraftment. While Aloe vera extract (AVE) possesses renoprotective properties, its bioactive compounds suffer from low bioavailability and instability. The study developed and characterized two nanoformulations of AVE; carrier-free nanoparticles (AVENPS) and chitosan-encapsulated nanoparticles (AVE-CSNPS), to enhance mesenchymal stem cells (MSCs) therapy for amikacin-induced kidney injury. In vitro bioactivities (antioxidant, anti-inflammatory, anticoagulant, and cytotoxicity) were evaluated for both nanoformulations. For in vivo assessment, amikacin-induced AKI mice received: MSCs alone, MSCs + AVE, MSCs + AVENPS, MSCs + CSNPS or MSCs + AVE-CSNPS. Phytochemical characterization revealed both formulations preserved key bioactive compounds, with AVE-CSNPS showing superior retention of flavonoids and essential minerals. Physicochemical analysis demonstrated AVE-CSNPS had optimal characteristics for drug delivery, including larger hydrodynamic size, higher positive zeta potential, and enhanced stability (PDI < 0.3). In vitro, AVE-CSNPS exhibited significantly stronger antioxidant, anti-inflammatory, and anticoagulant effects compared to AVENPS, while showing lower cytotoxicity. In vivo, the MSCs + AVE-CSNPS combination therapy most effectively restored kidney function, normalized oxidative stress markers and pro-inflammatory cytokines. These results demonstrated chitosan encapsulation significantly enhanced Aloe vera’s therapeutic potential and MSCs synergy, offering a promising nano-enabled strategy for renal regeneration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-20918-6.