Amphotericin B-PEG Conjugates of ZnO Nanoparticles: Enhancement Antifungal Activity with Minimal Toxicity

Saad M Alshahrani; El-Sayed Khafagy; Yassine Riadi; Ahmed Al Saqr; Munerah M Alfadhel; Wael A H Hegazy

doi:10.3390/pharmaceutics14081646

Amphotericin B-PEG Conjugates of ZnO Nanoparticles: Enhancement Antifungal Activity with Minimal Toxicity

Pharmaceutics. 2022 Aug 7;14(8):1646. doi: 10.3390/pharmaceutics14081646.

Authors

Saad M Alshahrani¹, El-Sayed Khafagy^{1

2}, Yassine Riadi³, Ahmed Al Saqr¹, Munerah M Alfadhel¹, Wael A H Hegazy^{4

5}

Affiliations

¹ Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
² Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
³ Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁴ Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
⁵ Department of Pharmaceutical Sciences, Pharmacy Program, Oman College of Health Sciences, Muscat 113, Oman.

Abstract

Amphotericin B (AMB) is commonly used to treat life-threatening systemic fungal infections. AMB formulations that are more efficient and less nephrotoxic are currently unmet needs. In the current study, new ZnO-PEGylated AMB (ZnO-AMB-PEG) nanoparticles (NPs) were synthesized and their antifungal effects on the Candida spp. were investigated. The size and zeta potential values of AMB-PEG and ZnO-AMB-PEG NPs were 216.2 ± 26.9 to 662.3 ± 24.7 nm and -11.8 ± 2.02 to -14.2 ± 0.94 mV, respectively. The FTIR, XRD, and EDX spectra indicated that the PEG-enclosed AMB was capped by ZnO, and SEM images revealed the ZnO distribution on the surface NPs. In comparison to ZnO-AMB NPs and free AMB against C.albicans and C.neoformans, ZnO-AMB-PEG NPs significantly reduced the MIC and MFC. After a week of single and multiple dosage, the toxicity was investigated utilizing in vitro blood hemolysis, in vivo nephrotoxicity, and hepatic functions. ZnO-AMB-PEG significantly lowered WBC count and hematocrit concentrations when compared to AMB and ZnO-AMB. RBC count and hemoglobulin content, on the other hand, were unaltered. ZnO-AMB-PEG considerably lowered creatinine and blood urea nitrogen (BUN) levels when compared to AMB and ZnO-AMB. The difference in liver function indicators was determined to be minor by all formulae. These findings imply that ZnO-AMB-PEG could be utilized in the clinic with little nephrotoxicity, although more research is needed to determine the formulation's in vivo efficacy.

Keywords: PEGylation; ZnO; amphotericin; antifungal; metallic nanoparticles.

Grants and funding

The work was supported by the Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research work through project number (IF-PSAU-2021/03/18826).