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

Research output: Contribution to journalArticlepeer-review

Mohamed Hamdi, Enas Elmowafy, Hend Mohamed Abdel-Bar, Akram M. ElKashlan, Khuloud T. Al-Jamal, Gehanne A.S. Awad

Original languageEnglish
Pages (from-to)731-747
Number of pages17
JournalInternational Journal of Biological Macromolecules
Published30 Sep 2022

Bibliographical note

Funding Information: H.A. is a recipient of Newton Musharafa Fellowship. Graphical abstract and Scheme 1 are constructed by Biorender. Publisher Copyright: © 2022 The Authors

King's Authors


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.

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