Bicontinuous cubic phase nanoparticle lipid chemistry affects toxicity in cultured cells

Abstract

Gaining an increased understanding of the toxicity of new lipid nanoparticle formulations such as the class of cubic and hexagonal phase forming nanomaterials called cubosomes™ and hexosomes™ is crucial for their development as therapeutic agents. Surprisingly, the literature on the in vitro and in vivo toxicity of cubic and hexagonal phase forming lipid nanoparticles is negligible, despite a rapidly growing number of publications on their potential use in various therapeutic applications. In this work we have developed methods to study the in vitro cytotoxicity of two chemically distinct cubic phase nanoparticle dispersions using the lipids glycerol monooleate and phytantriol respectively. We have found that the toxicity of phytantriol cubosomes is considerably greater than that of glycerol monooleate cubosomes.The increased toxicity of phytantriol appears to result from its greater ability to disrupt the cellular membrane (haemolytic activity) and oxidative stress. This finding has significant impact and can provide useful guidelines for those conducting further research on the use of cubic phase forming lipids for therapeutic and diagnostic applications both in vitro and in vivo. † Electronic supplementary information (ESI) available. See

Perspective on Nanoparticle Technology for Biomedical Use

“…The highest ROS activity per unit area was observed for 30 nm TiO 2 particles, whereas, the trend for crystal phase was amorphous followed by anatase, anatase-rutile mixture and rutile. Similar observations of crystal phase, chemical composition and size were also reported by other research groups [112–114]. To minimize the toxicity of nanoparticles, either biocompatible base materials or surface modification by several surface coating agents must be used and are discussed in the following section of this article.…”

Development and Optimization of Orally and Topically Applied Liquid Crystal Drug Formulations

“…It has a larger surface area to interact with biological membranes with high fluidity, and greater amounts of drugs can be incorporated independent of their solubility. In contrast to our findings, other studies have demonstrated the presence of cubosomes using different types of LCforming lipids such as glyceryl monooleate GMO or phytantriol PHT 10,22 . We strongly believed that several factors might affect the phase structure of LC formulations, such as temperature, type of LC-forming lipid, physiochemical properties of the entrapped drugs, lipid concentration, and type of surfactant.…”

Nanostructure and cytotoxicity of self-assembled monoolein–capric acid lyotropic liquid crystalline nanoparticles

“…38 However, in order to design a more effective drug delivery carrier, it is essential to understand the phase behavior of MO under the inuence of factors such as temperature, chemical environment, water content, and charge. 43 The results showed that MO cubosomes affected the viability of Chinese hamster ovary (CHO) and human alveolar basal epithelial (A549) cell lines differently. 39 It is interesting that only a small number of studies have focused on investigating the toxicity of nanoparticle dispersions made from lyotropic liquid crystal phase forming lipids.…”