Fabrication and evaluation of nanocontainers for lipophilic anticancer drug delivery in 3D in vitro model

Abstract

Presently, most of anticancer drugs are high toxic for normal cells and, and as a result, they have severe side effects. Moreover, most of the formulations are lipophilic and have poor selectivity. To overcome these limitations, various drug delivery systems could be proposed. The aim of the current study was to fabricate novel polysaccharide nanocontainers (NC) by one‐step ultrasonication technique and to evaluate their accumulation efficacy and cytotoxicity in 2D (monolayer culture) and 3D (tumor spheroids) in vitro models. NC with mean sizes in a range of 340–420 nm with the core‐shell structure are synthetized and characterized. The NC shell is composed from diethylaminoethyl dextran/xanthan gum polyelectrolyte complex, while the hydrophobic core was loaded with the lipophilic anticancer drug thymoquinone. To enhance NC accumulation in human breast adenocarcinoma MCF‐7 cells, the NC surface was modified with poly‐L‐lysine (PLL) or polyethylene glycol. Cell uptake of the NC loaded with Nile Red into the tumor cells was investigated by laser scanning confocal microscopy, fluorescent flow cytometry and fluorimetry. Modification of the NC with PLL allowed to obtain the optimal drug delivery system with maximal cytotoxicity, which was tested by MTT‐test. The developed NC are promising for lipophilic anticancer drug delivery.

Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

“…A co-liposphere of Cabazitaxel (CBZ) and TQ was made of vitamin E-TPGS tricaprin, and egg phosphatidylcholine improved cellular internalization, which potentiates dose-dependent apoptosis as well as anticancer efficacy against MDA-MB-231 and MCF-7 cell lines [ 176 ]. The poly-L-lysine (PLL) and polyethylene glycol surface-decorated nanocontainers (NC-PLL) complex of diethylaminoethyl dextran/xanthan gum enhanced intracellular accumulation of TQ [ 177 ]. The positive surface charge of the NC-PLL significantly favored nanocontainer binding on the negatively charged cell membrane as compared to nonmodified nanocontainers, resulting in negatively charged NC-PEG.…”

Transfection efficacy and drug release depends upon the PEG derivative in cationic lipoplexes: Evaluation in 3D in vitro model and in vivo

“…Recently, we have developed a simple universal approach based on RGD‐induced cell self‐assembly technique 21 . This approach has been already successfully used by us to generate multicellular spheroids from different tumor cells 31–33 as well as coculture spheroids from tumor and healthy (normal) cells 34 …”

“…Recently, we have developed a simple universal approach based on RGD-induced cell self-assembly technique. 21 This approach has been already successfully used by us to generate multicellular spheroids from different tumor cells [31][32][33] as well as coculture spheroids from tumor and healthy (normal) cells. 34 After 1 h incubation, the PEGylated liposomes were found to be attached to the outer spheroid surface, while after 3 h incubation they were already observed everywhere within the spheroid, including its center.…”

Xanthan: enzymatic degradation and novel perspectives of applications

“…Functional materials based on xanthan can be used to create drug delivery systems (Cortes et al 2020 ). Polysaccharide nanocontainers (NC) composed of a xanthan/diethylaminoethyl polyelectrolyte complex have been developed for the delivery of the lipophilic antitumor drug thymoquinone (Borodina et al 2021 ). The complex does not show the lipophilic properties that often lead to high toxicity in antitumor drugs.…”