Abstract
Glyceryl monooleate (GMO) is one of the most popular amphiphilic lipids, which, in the presence of different amounts of water and a proper amount of stabilizer, can promote the development of well defined, thermodynamically stable nanostructures, called lyotropic liquid crystal dispersions. The aim of this study is based on the design, characterization, and evaluation of the cytotoxicity of lyotropic liquid crystal nanostructures containing a model anticancer drug such as doxorubicin hydrochloride. The drug is efficiently retained by the GMO nanosystems by a remote loading approach. The nanostructures prepared with different non-ionic surfactants (poloxamers and polysorbates) are characterized by different physico-chemical features as a function of several parameters, i.e., serum stability, temperature, and different pH values, as well as the amount of cryoprotectants used to obtain suitable freeze-dried systems. The nanostructures prepared with poloxamer 407 used as a stabilizer show an increased toxicity of the entrapped drug on breast cancer cell lines (MCF-7 and MDA-MB-231) due to their ability to sensitize multidrug-resistant (MDR) tumor cells through the inhibition of specific drug efflux transporters. Moreover, the interaction between the nanostructures and the cells occurs after just a few hours, evidencing a huge cellular uptake of the nanosystems.
Highlights
Glyceryl monooleate (GMO) is often described as a special lipid that plays an important role in drug delivery systems, due to its ability to self-assemble in water and to form a variety of well-defined, thermodynamically stable liquid crystal structures [1]
The peculiar features of nanostructures prepared with PL F-127 highlight the great potential of these systems to encapsulate and modulate the release of doxorubicin hydrochloride
When the remote loading approach is used to improve the efficiency of the entrapment of the bioactive by the nanostructures, a high retention rate of doxorubicin hydrochloride (DOX) is promoted in the vesicles, favoring a constant and prolonged drug release over 72 h
Summary
Glyceryl monooleate (GMO) is often described as a special lipid that plays an important role in drug delivery systems, due to its ability to self-assemble in water and to form a variety of well-defined, thermodynamically stable liquid crystal structures [1]. In the presence of a proper stabilizer [6], liquid crystal phases can be arranged in different supramolecular structures such as cubosomes [7,8] or hexosomes [9,10,11], which could potentially be used for intravenous injection This is because of their scarce viscosity as well as their ability to maintain the internal nanostructure of the bulk systems and keep it intact. The excellent characteristics of these hosting matrices make these nanostructures excellent and promising carriers for various applications in the drug delivery field [13]
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