Study of Animals About Borneol and Folic Acid Co-modified Doxorubicin Loaded PAMAM Complex in Vivo

OBJECTIVE To design a multifunctional targeting strategy FA-BO-PAMAM/DOX, in which a novel targeting drug carrier(FA-BO-PAMAM) based on the poly (amido amine)(PAMAM) G5 dendrimer modified with borneol(BO) and folic acid(FA) molecules on the periphery and doxorubicin(DOX) loaded in the interior, so as to increase drug delivery in gliomas. METHODS BO and FA molecules was covalent bound on the PAMAM G5 dendrimer, so as the carrier of FA-BO-PAMAM was synthesized. Then DOX was loaded into the carrier, the FA-BO-PAMAM/DOX was prepared. Besides, pharmacokinetic and tissue biodistribution in vivo were evaluated on tumor bearing rats after caudal vein injection with FA-BO-PAMAM/DOX. RESULTS In comparison with DOX solution, groups of BO-PAMAM/DOX and FA-BO-PAMAM/DOX displayed significant longer t_1/2 and blood retention time(P<0.01), with prolonged AUC(P<0.01). Furthermore, drug content was higher in tumor and lower in heart of the groups of BO-PAMAM/DOX and FA-BO-PAMAM/DOX compared with DOX. CONCLUSION After DOX is loaded in to the prepared carrier FA-BO-PAMAM, part of the pharmacokinetic parameters of DOX can be changed significantly, so that the drug can be maintained in plasma longer. FA-BO-PAMAM/DOX exhibits higher tumor inhibition ratio and lower cardiotoxicity, indicating that FA-BO-PAMAM/DOX has clinic value on improving the treatment index of DOX.