Lipid-coated hollow mesoporous silica nanospheres for co-delivery of doxorubicin and paclitaxel: Preparation, sustained release, cellular uptake and pharmacokinetics

Abstract

A carrier consisting of lipid-coated hollow mesoporous silica nanospheres (L-HMSN) was produced for the combination of the water-insoluble drug (paclitaxel, PTX) and the water-soluble drug (doxorubicin, DOX). DOX was adsorbed into the nanoscale hollow structure of the hollow mesoporous silica nanospheres (HMSN) by adsorption and PTX was wrapped in the phospholipid layer of the HMSN surface by lipid film hydration method. The characterization results showed that DOX and PTX were present in the nanopheres in an amorphous state. The loaded L-HMSN (DOX/PTX@L-HMSN) in vitro drug release showed a sustained release in phosphate buffered solution (PBS) at pH6.8 and 0.001%SDS. The cellular uptake experiment indicated that L-HMSN was successfully taken up by A549 cells. In addition, the combination of DOX and PTX in L-HMSN exhibited a marked synergistic effect in inhibiting the proliferation of A549 cells. The pharmacokinetic study demonstrated that L-HMSN could significantly improve the relative bioavailability of DOX and PTX. These results confirm that L-HMSN is a promising carrier for successful drug combination.