Pyrazinamide-Loaded Pegylated Polypropylene Imine Dendritic Architecture for Reducing Haemolytic Toxicity

Author: Valli Manalan. B., Arul. B. and Kothai

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Abstract

The purpose of the current study was to construct a Pyrazinamide loaded PEGylated fifth generation (5.0G) Poly (Propylene) Imine (PPI) dendrimer and compare its potential haemolytic toxicity. Pyrazinamide (PZA) is a drug that is used to treat Tuberculosis (TB). The dendrimers exhibit superior performance in targeted drug delivery, yet haemolytic toxicity produced by dendrimers can cause acute renal failure. Henceforth, the present research researches the synthesis of dendrimers along with enhanced biocompatibility that aids in reducing haemolytic toxicity concerning dendrimers-mediated drug delivery. The free 5.0G PPI dendrimer, synthesised Pyrazinamide loaded PEGylated fifth generation PPI dendrimer, and PEGylated 5.0G PPI dendrimer are considered as subjects of haemolytic toxicity investigation. UV-spectrophotometric analysis at 269 nm (n=3) calculated the amount of liberated haemoglobin from RBC, and the haemolysis degree was equated with it. Several research findings have revealed that PEGylation is suitable for modifying the core Ethylene Diamine (EDA)-PPI dendrimers of ethylene diamine initiator. According to comparative haemolytic toxicity experiments, the toxicity of free dendrimer was found to be 20.39 0.82, PEGylated dendrimer was 2.72 1.10, and Pyrazinamide loaded PEGylated 5.0G PPI dendrimer was 1.420.52 each. In this work, synthetic systems' haemolytic toxicity levels are lower and can provide bio-actives. Finally, this study conducted ex vivo and in vivo experiments and proved that haemolytic toxicity is reduced in Pyrazinamide Loaded PEGylated 5.0G PPI Dendrimers and drug circulation time is maximised.

Keywords

PPI dendrimers, Pyrazinamide, drug delivery, Haemolytic toxicity, PEGylation

Conclusion

Dendrimers emerge as excellent drug carriers, but their toxicity limits their usage in the medical field. Hence, the research on haemolytic toxicity will be of greater significance for the safe application of dendrimers as the drug carrier system. Dendrimers toxicity relies upon various factors such as generation, size, surface charge, etc. Among the classes of dendrimers, PPI dendrimer remains the most recognised one. In addition to it, dendrimers can improve drug efficiency. Several types of research are being conducted to reduce the haemolytic toxicity in dendrimers by introducing various chemical modifications upon the surface. Hence, this research utilises the pyrazinamide drug, which is used for treating tuberculosis and is loaded into the PPI dendrimer to enhance its efficacy and decrease dendrimer toxicity. The PEGylation is discovered as the appropriate surface modification technique to reduce the haemolytic toxicity in 5.0G PPI dendrimer. The study utilises the EDA as the initiator core for synthesising 5.0G PPI dendrimer and finally loaded the Pyrazinamide. Hence, the Pyrazinamide loaded. PEGylated 5.0 G PPI exhibits low toxicity compared to the free fifth-generation PPI and PEGylated PPI dendrimer. Also, the study was conducted in vivo. Ex vivo experiments revealed lower toxicity levels in Pyrazinamide loaded PEGylated 5.0 G PPI. Through this synthesis.

References

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How to cite this article

Valli Manalan. B., Arul. B. and Kothai (2023). Pyrazinamide-Loaded Pegylated Polypropylene Imine Dendritic Architecture for Reducing Haemolytic Toxicity. Biological Forum – An International Journal, 15(6): 795-800.