Potential oral delivery of 7-Ethyl-10-hydroxy-camptothecin (SN-38) using poly(amidoamine) dendrimers

Purpose. To investigate potential application of poly(amidoamine) (PAMAM) dendrimers for improving the delivery of SN-38. Methods. Complexes of SN-38 with generation 4 amine terminated PAMAM dendrimers were synthesized with varying amounts of drug. Stability of the complexes as well as influence of complexation on permeability across and cellular uptake by Caco-2 cells was evaluated. Results. The complexes were stable at pH 7.4 and drug was released at pH 5. A tenfold increase in permeability and more than hundredfold increase in cellular uptake of the complexes with respect to free SN-38 was observed. Conclusions. Studies suggest that complexation with PAMAM dendrimers has the potential to improve the oral bioavailability of SN-38.