4.7 Article

CD44 mediated colon cancer targeting mutlifaceted lignin nanoparticles: Synthesis, in vitro characterization and in vivo efficacy studies

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 643, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.ijpharm.2023.123270

Keywords

Lignin nanoparticles; Active targeting; Hyaluronic acid; Solid tumor; Mitochondrial depolarization; hyaluronan/CD44 receptors

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Hyaluronic acid (HA) coated irinotecan loaded lignin nanoparticles (HDLNPs) were synthesized and characterized for their targeted chemotherapeutic potential. The studies demonstrated improved chemotherapeutic efficacy, antioxidant activity, and prolonged drug localization in tumor sites using HDLNPs. Additionally, HDLNPs were found to prevent irinotecan-associated side effects and maintain stability over a long period.
Hyaluronic acid (HA) coated irinotecan loaded lignin nanoparticles (HDLNPs) were synthesized using ionic interaction method. Optimized nanoparticles were characterized for their active chemotherapeutic targeting potential to CD44 receptors overly-expressed on cancer cells. Blood component interaction studies supported hemocompatible nature of HDLNPs and also demonstrated their sustained plasma residence property. Cell antiproliferation and mitochondrial depolarization studies on HT-29 cells suggest significantly (p < 0.01) improved chemotherapeutic efficacy of HDLNPs. In vitro cell based studies showed that nanoparticles have retained antioxidant activity of lignin that can prevent cancer relapse. In vivo biodistribution studies in tumor-bearing Balb/c mice confirmed improved drug localization in tumor site for longer duration. Tumor regression and histopathological studies indicated the efficacy ofligand-assisted targeting chemotherapy over the conventional therapy. Hematological and biochemical estimation suggested that irinotecan-associated myelosuppression, liver steatosis and rare kidney failure can be avoided by its encapsulation in HA-coated lignin nanoparticles. HDLNPs were found to be stable over a period of 12 months.

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