In vitro and in vivo Assessment of a Generic Form of Albumin-bound Paclitaxel Nanoparticle in Rat
Maryam Dibaei, Behjat Sheikholeslami, Hoda Lavasani, Navid Godarzi, Nastaran Hosseinifar, Mohammad-Reza RouiniIntroduction:
Paclitaxel is widely recognized as a highly effective antineoplastic drug. This study aimed to compare the preclinical pharmacokinetics of the developed NP with two clinically used formulations, Abraxane® and Taxol®
Methods:
An albumin-bound nanoparticle formulation of paclitaxel without Cremophor was designed. For in vitro assessment, particle size, XRD, DSC, and release tests were evaluated. Pharmacokinetic properties of the prepared formulation were compared with those of two formulations currently used in clinical practice after IV administration to rats.
Results:
XRD and DSC analyses confirmed the transition of paclitaxel powder from crystalline to amorphous. Quantitative assessment of paclitaxel revealed a rapid decrease in plasma concentration, with the two NP formulations showing a faster decline than Taxol®. Taxol® demonstrated a higher AUC0-t (19646.03 ± 3123.58 ng.h/mL) compared to NP albumin-bound paclitaxel and Abraxane® (654.94 ± 39.35 and 638.29 ± 115.29 ng.h/mL, respectively).
Discussion:
Kel was consistent between the two albumin-bound formulations, both of which demonstrated a stable rate (~0.06 h-1 ) at which the removal of paclitaxel from systemic circulation occurs. This indicates that both albumin-based paclitaxel formulations show comparable pharmacokinetic and clearance patterns. On the other hand, the higher Kel observed compared to Taxol® suggests an increased systemic clearance, potentially establishing the difference in distribution, exposure, and safety profile associated with the Cremophor-lacking formulation.
Conclusion:
The albumin-bound paclitaxel formulations, i.e. NP albumin-bound paclitaxel and Abraxane®, exhibit similar and consistent patterns of kinetics regarding elimination and a fixed rate of systemic clearance higher than that of Taxol®.