Hyaluronic acid-entecavir conjugates-core/lipid-shell nanohybrids for efficient macrophage uptake and hepatotropic prospects

Drug covalently bound to polymers had formed, lately, platforms with great promise in drug delivery. These drug polymer conjugates (DPC) boosted drug loading and controlled medicine release with targeting ability. Herein, the ability of entecavir (E) conjugated to hyaluronic acid (HA) forming the core of vitamin E coated lipid nanohybrids (EE-HA LPH), to target Kupffer cells and hepatocyte had been proved. The drug was associated to HA with efficiency of 93.48 ± 3.14 % and nanohybrids loading of 22.02 ± 2.3 %. DiI labelled lipidic nanohybrids improved the macrophage uptake in J774 cells with a 21 day hepatocytes retention post intramuscular injection. Finally, in vivo biocompatibility and safety with respect to body weight, organs indices and histopathological alterations were demonstrated. Coating with vitamin E and conjugation of E to HA (a CD44 ligand), could give grounds for prospective application for vectored nano-platform in hepatitis B. [Display omitted] •Hyaluronic acid was efficiently conjugated to entecavir.•Vitamin E coated hyaluronic-entecavir nanohybrids were successfully fabricated.•Nanohybrids exhibited suitable particle size for liver targeting.•Nanohybrids showed a high drug association and one-month controllable release.•Nanohybrids displayed proficient macrophage retention and in vivo distribution.