Lipid-
polymer hybrid nanoparticles (NPs) combining the positive attributes of both
liposomes and polymeric NPs are increasingly being considered as promising candidates to carry therapeutic agents safely and efficiently into targeted sites. Herein, a modified emulsification technique was developed and optimized for the targeting
lipid-
polymer hybrid NPs fabrication; the surface properties and stability of the hybrid NPs were systematically investigated, which confirmed that the hybrid NPs consisted of a
poly (lactide-co-glycolide) core with ∼90% surface coverage of the
lipid monolayer and a ∼4.4 nm hydrated
polyethylene glycol (PEG) shell. Optimization results showed that the
lipid:
polymer mass ratio and the
lipid-PEG:
lipid molar ratio could affect the size,
lipid association efficiency and stability of hybrid NPs. Furthermore, a model
chemotherapy drug,
10-hydroxycamptothecin, was encapsulated into hybrid NPs with a higher drug loading compared to PLGA NPs. Surface modification of the
lipid layer and the PEG conjugated targeting
ligand did not affect their drug release kinetics. Finally, the cytotoxicity and cellular uptake studies indicated that the
lipid coverage and the c(RGDyk) conjugation of the hybrid NPs gained a significantly enhanced ability of cell killing and endocytosis. Our results suggested that
lipid-
polymer hybrid NPs prepared by the modified
emulsion technique have great potential to be utilized as an engineered drug delivery system with precise control ability of surface targeting modification.