Nanoparticle drug delivery enhances the cytotoxicity of hydrophobic-hydrophilic drug conjugates

We report a drug conjugation approach to concurrently load both hydrophobic and hydrophilic drugs into the same drug delivery nanocarrier in a precisely controllable manner. Using paclitaxel as a model hydrophobic drug and cisplatin as a model hydrophilic drug, we demonstrate the synthesis and characterization of a paclitaxel-cisplatin conjugate via a hydrolysable linker and its easy encapsulation by a lipid-polymer hybrid nanoparticle with controllable drug loading yield and drug release profile. The cytotoxicity of the resulting drug conjugate loaded nanoparticles against human ovarian cancer cells is investigated and compared to that of unencapsulated free drug conjugates. It is found that the cellular cytotoxicity of the hydrophobic-hydrophilic drug conjugates is significantly improved after being encapsulated into the nanoparticles. This is likely because the nanoparticles facilitate the intracellular entry of the amphiphilic drug conjugates and thus overcome their poor transport ability across the lipid bilayer structured cellular membranes.