Development of controlled release microspheres for targeted drug delivery system using camptothecin as a model drug: An in vitro-in vivo correlation

Camptothecin is an antitumor agent which upon intravenous administration exists as both the lactone and the carboxylate forms. While the lactone form is active, the carboxylate form is inactive but toxic. The lactone and the carboxylate forms of the drug were analyzed individually using an isocratic reversed phase HPLC method. The lower limits of detection for lactone and carboxylate was 0.1 ng/mL and 1 ng/mL respectively.; Microspheres were prepared using camptothecin, bovine serum albumin and magnetite. In vitro dissolution studies were carried out for 7 days in phosphate buffer at pH 7.4. Particle size and shape analysis were conducted using an electron microscope. The results indicated that the release of camptothecin was affected by oil used, stirring speed, and duration of heating. Electro micrographs at 10,000 X magnification showed the spheres to be spherical and separated. In vitro studies showed that the microspheres were magnetically responsive.; This study demonstrated that magnetically responsive albumin microspheres containing camptothecin can be reliably targeted to the desired site in a rat model. In addition, the targeted microspheres remained localized for many hours after removal of the magnetic field; this suggested that the microspheres were engulfed within the cells and the drug released at the site.; Three different controlled released camptothecin microsphere formulations and a solution of camptothecin were injected (0.5 mg/kg) slowly, intraperitoneally. Two compartment model was employed to determine the pharmacokinetic parameters. Statistical analysis at 95% confidence interval established that there was a significant difference (p {dollar}<{dollar} 0.5) in the {dollar}rm tsb{lcub}1/2beta{rcub}, alpha, beta, Csb{lcub}max{rcub}, Tsb{lcub}max{rcub},{dollar} and (AUC){dollar}sb0spinfty{dollar} following the administration of camptothecin in a solution form and in controlled release microsphere formulations. In vitro-in vivo correlation was obtained when K{dollar}sb{lcub}rm a{rcub}{dollar} and C{dollar}sb{lcub}rm max{rcub}{dollar} values were individually correlated with in vitro release rate constant (K), with the regression coefficient of 0.998 and 0.87, respectively.