Background: Improving poorly soluble drugs into druggability was a major problem faced
by pharmaceutists. Nanosuspension can improve the druggability of insoluble drugs by improving the
solubility, chemical stability and reducing the use of additives, which provided a new approach for the
development and application of the insoluble drugs formulation. Paclitaxel (PTX) is a well-known BCS
class IV drug with poor solubility and permeability. Also, many studies have proved that paclitaxel is a
substrate of the membrane-bound drug efflux pump P-glycoprotein (P-gp), therefore it often shows
limited efficacy against the resistant tumors and oral absorption or uptake.
Objective: To manufacture an enhanced-penetration PTX nanosuspension (PTX-Nanos), and evaluate
the physicochemical property, pharmacokinetics and tissue distribution in vivo and cytotoxic effect
Methods: PTX-Nanos were prepared by microprecipitation-high pressure homogenization, with a
good biocompatibility amphiphilic block copolymer poly(L-phenylalanine)-b-poly(L-aspartic acid)
(PPA-PAA) as stabilizer.
Results: The PTX-Nanos had a sustained-dissolution manner and could effectively reduce plasma peak
concentration and extend plasma circulating time as compared to PTX injection, markedly passively
targeting the MPS-related organs, such as liver and spleen. This unique property might enhance treatment
of cancer in these tissues and reduce the side effects in other normal tissues. Moreover, the hybrid
stabilizers could enhance penetration of PTX in PTX-Nanos to multidrug resistance cells.
Conclusion: To sum up, our results showed that the optimal formula could improve the solubility of
PTX and the stability of the product. The PTX-Nanos developed in this research would be a promising
delivery platform in cancer treatment.