Abstract

We used a hydrogel-mediated dual drug delivery approach, based on an injectable glycol chitosan (GC) hydrogel, doxorubicin hydrochloride (DOX⋅HCl), and a complex of beta-cyclodextrin (β-CD) and paclitaxel (PTX) (GDCP) for breast cancer therapy in vitro and in vivo. The hydrogel was swollen over 3 days and remained so thereafter. After an initial burst period of 7 hours, the two drugs were released in a sustained manner for 7 days. The in vitro cell viability test showed that GDCP had a better anticancer effect than well plate and DOX⋅HCl/PTX (DP). In addition, the in vivo tests, which evaluated the anticancer effect, systemic toxicity, and histology, proved the feasibility of GDCP as a clinical therapy for breast cancer.

Highlights

  • Breast cancer is one of the most common cancers in women worldwide

  • The results demonstrated that GDCP resulted in more rapid release of doxorubicin hydrochloride (DOX·HCl) and PTX than GDP owing to the effects of β-CD and swollen glycol chitosan (GC) hydrogel in aqueous solution (Figures 1 and 2)

  • GC (≥60% calculated by titration, crystalline, MW ≈ 585,000 g/mol) and glycidyl methacrylate (GM) for visible-light-cured hydrogel preparation were purchased from Sigma-Aldrich

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Summary

Introduction

Breast cancer is one of the most common cancers in women worldwide. Owing to the presence of lymph nodes next to the breast, metastasis of breast cancer often occurs in younger people with active cell proliferation [1]. Most known chemotherapies are accompanied by side effects, such as vomiting, anorexia, and hair loss, because the drugs affect both cancer cells and normal cells [2] To overcome these problems, there have been many studies of systemic drug delivery systems using intravenous injection of nanoparticles [3]. There have been many studies of systemic drug delivery systems using intravenous injection of nanoparticles [3] These nanoparticles face environmental changes, such as changes in pH and salt conditions, and come in contact with various plasma proteins in the blood stream; these environmental factors destabilize nanoparticles through changes in the thermodynamic or kinetic equilibrium [4]. Visible-light-cured glycol chitosan (GC) hydrogel was prepared as a local drug delivery system, and this platform was found to have potential for several solid cancer therapies [6,7,8]

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