In Vitro and in Vivo Evaluation of Novel Dtx-Loaded Multifunctional Heparin-Based Polymeric Micelles Targeting Folate Receptors and Endosomes Publisher Pubmed

Summary: Research shows heparin-based nanoparticles improve cancer drug delivery, reducing tumor growth with less toxicity. #CancerResearch #DrugDelivery

Kazemi M¹ ; Emami J¹ ; Hasanzadeh F² ; Minaiyan M³ ; Mirian M⁴ ; Lavasanifar A⁵ ; Mokhtari M⁶
Source: Recent Patents on Anti-Cancer Drug Discovery Published:2020

Abstract

Background: The development of biocompatible tumor-targeting delivery systems for anticancer agents is essential for efficacious cancer chemotherapy. Nanoparticles, as drug delivery cargoes for cancer therapy, are rapidly improving to overcome the limitations of conventional che-motherapeutic agents. Heparin–modified nanoparticles are currently being considered as one of the favorable carriers for the delivery of chemotherapeutics to cancer tissues. Objective: This study was aimed at evaluating the in vitro and in vivo antitumor activity of a novel targeted, pH-sensitive, heparin-based polymeric micelle loaded with the poorly water-soluble anti-cancer drug, docetaxel (DTX). The micelles could overcome the limited water solubility, non-spe-cific distribution, and insufficient drug concentration in tumor tissues. Methods: DTX-loaded folate targeted micelles were prepared and evaluated for physicochemical properties, drug release, in vitro cellular uptake and cytotoxicity in folate receptor-positive and fo-late receptor-negative cells. Furthermore, the antitumor activity of DTX-loaded micelles was evaluated in the tumor-bearing mice. Some related patents were also studied in this research. Results: The heparin-based targeted micelles exhibited higher in vitro cellular uptake and cytotoxic-ity against folate receptor over-expressed cells due to the specific receptor-mediated endocytosis. DTX-loaded micelles displayed greater antitumor activity, higher anti-angiogenesis effects, and lower systemic toxicity compared with free DTX in a tumor-induced mice model as confirmed by tumor growth monitoring, immunohistochemical evaluation, and body weight shift. DTX-loaded targeting micelles demonstrated no considerable toxicity on major organs of tumor-bearing mice compared with free DTX. Conclusion: Our results indicated that DTX-loaded multifunctional heparin-based micelles with de-sirable antitumor activity and low toxicity possess great potential as a targeted drug delivery system in the treatment of cancer. © 2020 Bentham Science Publishers.