Folate-targeted drug-delivery systems prepared by nano-comminution

BACKGROUND: The size reduction ability of conventional wet comminution has been improved by proper polymeric stabilizer systems, and the resulting nano-comminution methods have led to the commercialization of many poorly water-soluble drugs after improving their bioavailability. During nano-comminution, polymer steric stabilizers physically adsorb onto the surface of drug particles. METHOD: In this study, the cross-linking and subsequent functionalization methods of the physically adsorbed polymers were used to widen the applicability of the nano-comminution. Chitosan was used as a steric stabilizer for two hydrophobic drugs, naproxen and paclitaxel. RESULTS: Chitosan was successfully cross-linked (immobilized) by tripolyphosphate. The cross-linked stable polymer layer on drug nanoparticles was conjugated with folic acid, a model targeting moiety. The chemical reactions were performed without destroying the stabilities of drug nanosuspensions. The cross-linking and conjugation reactions significantly modified the release profiles of drug nanoparticles. CONCLUSION: This simple preparation method can be utilized to prepare novel drug encapsulations and folate-targeted delivery systems.