Investigation of pharmacokinetics and immunogenicity of magnetosomes

Abstract

Magnetosomes are iron oxide or iron sulphide nano-sized particles surrounded by a lipid bilayer synthesised by a group of bacteria known as magnetotactic bacteria (MTB). Magnetosomes have become a promising candidate for biomedical applications and could be potentially used as a drug-carrier. However, pharmacokinetics and immunogenicity of the magnetosomes have not been understood yet which preclude its clinical applications. Herein, we investigated the pharmacokinetics of magnetosomes including Absorption, Distribution, Metabolism, and Elimination (ADME) along with its immunogenicity in vitro and in vivo. The magnetosomes were conjugated with fluorescein isothiocyanate (Mag-FITC) and their conjugation was confirmed through fluorescence microscopy and its absorption in HeLa cell lines was evaluated using flow cytometry analysis. The results revealed a maximum cell uptake of 97% at 200 µg/mL concentration. Further, the biodistribution of Mag-FITC was investigated in vivo by a bioimaging system using BALB/c mice as a subject at different time intervals. The Mag-FITC neither induced death nor physical distress and the same was eliminated post 36 h of injection with meagre intensities left behind. The metabolism and elimination analysis were assessed to detect the iron overload which revealed that magnetosomes were entirely metabolised within 48-h interval. Furthermore, the histopathology and serum analysis reveal no histological damage with the absence of any abnormal biochemical parameters. The results support our study that magnetosomes were completely removed from the blood circulation within 48-h time interval. Moreover, the immunogenicity analysis has shown that magnetosomes do not induce any inflammation as indicated by reduced peaks of immune markers such as IL 1β, IL 2, IL 6, IL8, IFN γ, and TNF α estimated through Indirect ELISA. The normal behaviour of animals with the absence of acute or chronic toxicities in any organs declares that magnetosomes are safe to be injected. This shows that magnetosomes are benign for biological systems enrouting towards beneficial biomedical applications. Therefore, this study will advance the understanding and application of magnetosomes for clinical purposes.

Keywords:

• Magnetosomes
• pharmacokinetics
• immunogenicity
• biodistribution
• histopathology

Acknowledgment

The authors are thankful to Vellore Institute of Technology, Vellore for providing the necessary facilities to carry out this research.

Author contributions

Dr. K. Suthindhiran conceptualised the work on pharmacokinetics and immunogenicity of magnetosomes and performed a formal analysis of every step. The project administration and concerns regarding the resources were provided by Dr. K. Suthindhiran. Ms. M. Haripriyaa proceeded with the acquisition of data for all the analysis and validated the results. Ms. M. Haripriyaa was involved in manuscript preparation followed by drafting the work. After a series of critical evaluations, the raw data was converted into a manuscript, which was overseen and validated by Dr. K. Suthindhiran.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.