Cellular Interaction and Tumoral Penetration Properties of Cyclodextrin Nanoparticles on 3D Breast Tumor Model.

Gamze Varan,Gerrit Borchard,Viorica Patrulea,Erem Bilensoy

doi:10.3390/nano8020067

Gamze Varan, Gerrit Borchard + Show 2 more

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https://doi.org/10.3390/nano8020067

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Abstract

Amphiphilic cyclodextrins are biocompatible oligosaccharides that can be used for drug delivery especially for the delivery of drugs with solubility problems thanks to their unique molecular structures. In this paper, Paclitaxel was used as a model anticancer drug to determine the inclusion complex properties of amphiphilic cyclodextrins with different surface charge. Paclitaxel-loaded cyclodextrin nanoparticles were characterized in terms of mean particle diameter, zeta potential, encapsulation efficacy, drug release profile and cell culture studies. It was determined that the nanoparticles prepared from the inclusion complex according to characterization studies have a longer release profile than the conventionally prepared nanoparticles. In order to mimic the tumor microenvironment, breast cancer cells and healthy fibroblast cells were used in 3-dimensional (3D) cell culture studies. It was determined that the activities of nanoparticles prepared by conventional methods behave differently in 2-dimensional (2D) and 3D cell cultures. In addition, it was observed that the nanoparticles prepared from the inclusion complex have a stronger anti-tumoral activity in the 3D multicellular tumor model than the drug solution. Furthermore, polycationic amphiphilic cyclodextrin nanoparticles can diffuse and penetrate through multilayer cells in a 3D tumor model, which is crucial for an eventual antitumor effect.

Highlights

IntroductionSuccessful breast cancer treatment depends on efficient and safe delivery of chemotherapeutic agents to the tumor site
Breast cancer is the most common cancer in women comprising 30% among all types of cancer [1].Successful breast cancer treatment depends on efficient and safe delivery of chemotherapeutic agents to the tumor site
Anticancer activity of PCX loaded and blank amphiphilic cyclodextrin nanoparticles with different surface charge were evaluated by MCF-7 alone, HDF alone and MCF-7: HDF

Summary

Introduction

Successful breast cancer treatment depends on efficient and safe delivery of chemotherapeutic agents to the tumor site. Conventional chemotherapy is administered mainly through intravenous (IV) infusion and the anticancer drugs need to be in soluble form during this injection/infusion. Paclitaxel (PCX), which is the clinical first choice in breast cancer therapy, is practically insoluble in water. It needs to be formulated with co-solvents like Cremophor. The use of solubilizers was avoided with the United States Food and Drug Adminisration (FDA) approval of albumin nanoparticle bound PCX (Abraxane® ) in 2005 for breast cancer treatment at a significantly lower dose [3]. In a different formulation strategy, amphiphilic cyclodextrin nanoparticles were reported to protect PCX from recrystallization in aqueous dispersion thereby

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