Factors affecting drug encapsulation and stability of lipid-polymer hybrid nanoparticles

► Hybrid nanoparticles fail to form when oppositely charged lipid and drug are used. ► Hybrids are larger and have higher drug loading compared to non-hybrids. ► Drug loading of hybrids are influenced by antibiotic solubility and lipophilicity. ► In vitro release of hybrids are governed by the lipophilicity of the antibiotic. ► Hybrid nanoparticles are stable in buffer solutions only when TPGS is included.