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• W2893800767 abstract "Background: Plasma pharmacokinetic (PK) properties of oral or injectable drugs dictate whether the drug is clinically viable or not. Poor PK properties often result in termination of the development of the drug. Optimizing PK properties of drugs is a major challenge in the pharmaceutical industry. Ideally, sufficient circulating time of the drug in the plasma is required, so that it has adequate opportunity to reach the target tissue. Methods: We have used irinotecan, a known drug with poor PK properties, as a prototype to apply our idea of improving PK in plasma by PEGylation. We compared the PK profile of free irinotecan, irinotecan packaged in nanoparticles (NPs) with single polyethylene glycol (PEG) layer and irinotecan packaged in NPs with double PEG layer. PK properties of these formulations were compared in a zebrafish model when given intraperitoneally. Results: Dramatic differences in the PK properties of the three formulations were observed. The AUC, Cmax and T1/2 of irinotecan in each of these formulations differed from each other significantly. Approx. 4.5 - fold higher peak concentration (Cmax) and ~3 - fold higher exposure (AUC0-t) were observed for double PEGylated NPs as compared to free irinotecan and single PEGylated NPs. Conclusion: In summary, our data suggest that double PEGylation of NPs could be a very effective way to improve PK properties of drugs such as irinotecan." @default.
• W2893800767 created "2018-10-05" @default.
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• W2893800767 date "2019-08-20" @default.
• W2893800767 modified "2023-09-23" @default.
• W2893800767 title "Double PEGylation Significantly Improves Pharmacokinetic Properties of Irinotecan Containing Nanoparticles in a Zebrafish Model" @default.
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• W2893800767 doi "https://doi.org/10.2174/2468187308666180925143701" @default.
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