Formulation and Stability Evaluation of Structure-Altered Paclitaxel Nanosuspensions Stabilized by a Biocompatible Amino Acid Copolymer

摘要

To manufacture a stable paclitaxel nanosuspension (PTX-CP-Nanos), poly(L-phenyl-alanine)-b-poly(L-aspartic acid) (PPA-PAA), a multifunctional stabilizer, was synthesized via NCA-based ring-opening copolymerization. PTX-CP-Nanos were manufactured by a microprecipitation-high pressure homogenization method. X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) results indicated that the PTX in PTX-CP-Nanos existed in amorphous state. Particle size and zeta potential of the PTX-CP-Nanos were 226.8 +/- 2.1 nm and -28.4 +/- 0.1 mV, respectively, as indicated by dynamic light scattering method. Transmission electron microscopy (TEM) revealed that the morphology of PTX-CP-Nanos were of rod-like crystals. In addition, it was found that the structure of PTX-CP-Nanos altered to micelles by TEM during dissolution. The dissolution rate of PTX-CP-Nanos was significantly increased compared with the crude crystals but obviously lower than PTX injection, which could be ascribed to the particle size reduction of PTX nanoparticles and the conversion of PTX-CP-Nanos into micelles in the later stage of the dissolution test. The tests of storage stability, dilution stability and plasma stability both showed that PTX-CP-Nanos were significantly more stable than PTX-Nanos stabilized by other traditional surfactants and polymers. The acute toxicity tests demonstrated that PTX-CP-Nanos also had a high systemic safety.