1. Academic Validation
  2. Polylactic acid based polymeric nanoparticle mediated co-delivery of navitoclax and decitabine for cancer therapy

Polylactic acid based polymeric nanoparticle mediated co-delivery of navitoclax and decitabine for cancer therapy

  • Nanomedicine. 2022 Nov 18;102627. doi: 10.1016/j.nano.2022.102627.
Neha Mehrotra 1 Mohammad Anees 1 Sachchidanand Tiwari 1 Surender Kharbanda 2 Harpal Singh 3
Affiliations

Affiliations

  • 1 Centre for Biomedical Engineering, Indian Institute of Technology Delhi, India.
  • 2 Hillstream Biopharma, Inc. New Jersey, USA.
  • 3 Centre for Biomedical Engineering, Indian Institute of Technology Delhi, India; Department of Biomedical Engineering, All India Institute of Medical Sciences Delhi, India. Electronic address: [email protected].
Abstract

Combination chemotherapy with systemic administration of drugs in their free form can be challenging due to non-synchronized pharmacokinetics and sub-optimal tumor accumulation. The present study investigates a PLA-based block copolymeric nanocarrier for the co-delivery of navitoclax and decitabine (NAV/DCB NPs) for combination Cancer therapy. NAV/DCB NPs exhibited potent in vitro synergistic cytotoxicity in both acute myeloid leukemia and breast Cancer cell lines. Biodistribution studies of NAV/DCB NPs in tumor bearing mice, showed significant drug accumulation in tumor tissue and detectable quantities in plasma even after 48 h. Good hemocompatibility with reduced in vivo platelet toxicity indicated that encapsulation in PLA-based nanocarrier helped ameliorate navitoclax associated thrombocytopenia. In vivo biological activity of NAV/DCB NPs evaluated in xenograft AML and syngeneic breast Cancer model, demonstrated potent tumor growth inhibition efficacy. PLA-based NAV/DCB dual NPs present a novel, safe and effective nanoformulation for combination Cancer therapy in both solid tumors and hematologic malignancies.

Keywords

AML; Breast cancer; Combination nanomedicine; Decitabine; Navitoclax; cancer therapy.

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