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Keywords:

  • cyclodextrins;
  • nanospheres;
  • nanocapsules;
  • complexation;
  • NMR;
  • thermal analysis;
  • controlled release;
  • physical stability;
  • FTIR;
  • particle sizing

Abstract

In the current formulation of clinical use paclitaxel (PCX) is associated with solubilizers that may produce severe side effects. In this study, PCX was complexed to an amphiphilic cyclodextrin (CD), 6-O-CAPRO-β-CD, capable of forming nanoparticles spontaneously in order to mask its physicochemical properties via the formation of inclusion complexes of the drug with amphiphilic CD before the nanoparticle is formed. Complexes have been characterized with various techniques such as 1H NMR, Fourier Transform Infrared (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) confirming the formation of inclusion complex between PCX and 6-O-CAPRO-β-CD. Nanospheres and nanocapsules were prepared directly from the preformed PCX/6-O-CAPRO-β-CD inclusion complex by the nanoprecipitation technique, showing a size from 150 to 250 nm for nanospheres and from 500 to 500 nm for nanocapsules. Zeta potentials of the nanospheres and nanocapsules indicate stable colloidal dispersions within the range of −18 to −39 mV. A 12-month physical stability was demonstrated for blank nanoparticles. PCX encapsulation was high with three-fold increase in loading when nanoparticles are prepared directly from preformed inclusion complexes of the drug with 6-O-CAPRO-β-CD. In vitro liberation profiles of PCX from CD nanoparticles show a prolonged release profile for this drug up to 12 h for nanospheres and 24 h for nanocapsules. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1519–1529, 2008