(T1130-02-09) Design of Hyaluronic Acid-Coated Nanoliposomes for Active Targeting of Ibrutinib

Purpose: Ibrutinib (IBR) is a Bruton’s tyrosine kinase inhibitor (BTK), used for the treatment of B-cell lymphoma. IBR is BCS class II drug which has low solubility as well as low oral bioavailability that is < 4% because of first pass metabolism. Hyaluronic acid (HA) is a biocompatible and biodegradable linear polysaccharide which is of interest for tumor targeting through cell surface CD44 receptors. HA binds with high affinity to CD44 receptors, which are overexpressed in many tumors and involved in cancer metastasis. This research was aimed to develop liposomes of IBR to increase the delivery, cellular uptake, reduce toxicity to non-targeted area.

Methods: IBR loaded liposomes were prepared by thin film hydration method and evaluated for particle size, zeta potential, entrapment efficiency, drug release and hemolysis study.

Results: The particle size of IBR loaded liposomes and HA conjugated liposomes was 96.18±5.8 nm and 142.5±3.9 nm (Figure 1) as well as the zeta potential were -5.75±1.47 mV and -13.1±2.08 respectively. Encapsulation efficiency of the liposomes was 71.77±3.47%. TEM image of the liposomes and conjugated liposomes confirmed that the liposomes were of spherical shape. The Fluorescein isothiocyanate (FITC) loaded liposomes were found to be spherical shape (Figure 2). In vitro release data showed that HA conjugated liposomes extended the drug release in to the PBS pH 7.4. The hemolysis study exhibited good hemocompatibility of the liposomes. The pharmacokinetic performance was also improved with conjugated liposomes as compared to free drug.

Conclusion: The findings exhibited HA conjugated liposomes can be a promising approach for the treatment of B-cell lymphoma.

References: Sun D, Zhou JK, Zhao L, Zheng ZY, Li J, Pu W, Liu S, Liu XS, Liu SJ, Zheng Y, Zhao Y. Novel curcumin liposome modified with hyaluronan targeting CD44 plays an anti-leukemic role in acute myeloid leukemia in vitro and in vivo. ACS Applied Materials & Interfaces. 2017 May 24;9(20):16857-68.

Particle size of HA conjugated liposomes

FITC loaded liposomes