Introduction Due to the success of Abraxane® (albumin - paclitaxel nanoparticles), it is now clear that nanoparticles present a suitable method to deliver hydrophobic drugs. However, it must be acknowledged that, the poor colloidal stability, limited bioavailability and low payload are some of the shortcomings associated with Abraxane’s therapeutic effects. We have synthesized a new self-assembling polymer that encapsulate paclitaxel (PTX-N), exhibits good colloidal stability [stable at eq. PTX 1µg/mL], has a higher drug payload and is therapeutically active in experimental tumours. Methods The project was aimed at evaluating the pharmacokinetics (in rats) and tumouricidal activity (in 4T1 tumour bearing BALB/c mice) of PTX-N in comparison to two commercial paclitaxel formulations, Taxol® and Abraxane®. Results Colloidal Stability Abraxane® starts to dissociate below concentration eq. PTX 30 µg/mL, however, PTX-N is still stable at eq. PTX 1µg/mL from DLS data. Rat Pharmacokinetics study Following the intravenous injection of PTX-N, Taxol® and Abraxane® all at 10 mg kg-1 paclitaxel, the AUC0-72h of PTX-N and Abraxane® was 3.95 ± 0.95 and 2.17 ± 0.52 µg.h mL-1 with PTX-N showing a higher AUC0-72h than Abraxane.(p < 0.05). Biodistribution study 4T1 tumor-bearing mice were intravenously injected with all three formulations at a dose of 20 mg kg-1 paclitaxel. Table 1 data indicate that PTX-N delivers more drug to the tumour than Abraxane® (Table 1). Anti-tumour study On intravenous injection of paclitaxel in the three formulations to 4T1-tumour bearing mice, at a dose of 20mg kg-1 paclitaxel, tumor growth after treatment of PTX-N was significantly inhibited compared with other groups. (average tumour weight of PTX-N, Abraxane, Taxol and Saline group is 240, 341, 431 and 640mg, respectively) Conclusion PTX-N showed an improved delivery of paclitaxel to tumours and increased tumouricidal activity when compared to Abraxane and Taxol. Improving the colloidal stability of nanoparticle formulations is correlated with improvements in the tumouricidal activity of these nanoparticle formulations.

Paclitaxel-loaded nanoparticles, (PTX-N), exhibit superior tumor suppression versus Taxol® and Abraxane®.

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