[Use of cyclodextrins in the formulation of polyalkylcyanoacrylate nanoparticles charged with different active...

Cyclodextrins were used to improve the loading capacity of biodegradable pol(yisobutyl cyanoacrylat)e nanoparticles, which were obtained by anionic polymerization in aqueous medium. We investigated the feasibility of blank nanoparticles in the presence of a series of cyclodextrins (5 mg/ml) and poloxamer 188 (1%). The smaller particles (87 +/- 3 to 103 +/- 6 nm) were obtained in the presence of hydroxypropyl beta- or gamma-cyclodextrin. The nanoparticle loading capacity investigated in the presence of hydroxypropyl beta-cyclodextrin, in the previous conditions, on a series of steroids revealed an increase varying from 5.5 times (megestrol acetate) to 130 times (prednisolone). Differential scanning calorimetry study of the active ingredient (progesterone) in the nanoparticles, revealed an amorphous or molecular state. The in vitro release of the active ingredient occurred very rapidly but reached a plateau depending on the nanoparticle size and the dissolution medium nature. All the active ingredient was released in the presence of esterases. The addition of a preformed hydroxypropyl beta-cyclodextrin/saquinavir inclusion compound to the preparation medium of poly(isobutyl [or] isohexyl cyanoacrylate) nanoparticles, resulted in a 20-fold increase in the encapsulation yield. Presently, poly(isobutyl cyanoacrylate) hydroxypropyl beta-cyclodextrin combined nanoparticles loaded with doxorubicin are in phase II clinical trials.