pH Responsiveness of Hexosomes and Cubosomes for Combined Delivery of Brucea javanica Oil and Doxorubicin

Abstract

We report pH-responsive liquid crystalline lipid nanoparticles, which are dual loaded by Brucea javanica oil (BJO) and doxorubicin hydrochloride (DOX) and display a pH-induced inverted hexagonal (pH=7.4) to cubic (pH6.8) phase transition with a therapeutic application in cancer inhibition. Brucea javanica oil is a traditional herbal medicine that strongly inhibits the proliferation and metastasis of various cancers. Doxorubicin is an anti-tumor drug, which prevents DNA replication and hampers protein synthesis through intercalation between the base pairs of the DNA helices. Its dose-dependent cardiotoxicity imposes the need of safe delivery carriers.Here pH-induced changes in the structural and interfacial properties of designed multicomponent drug delivery (monoolein-oleic acid-BJO-DOX) systems are determined by synchrotron small-angle X-ray scattering (SAXS) and the Langmuir film balance technique. The nanocarrier assemblies displayed good physical stability in the studied pH range and adequate particle sizes and zeta potentials. Their interaction with model lipid membrane interfaces was enhanced under acidic pH conditions, which mimic the microenvironment around tumor cells. In vitro cytotoxicity and apoptosis studies with BJO-DOX dual-loaded pH-switchable liquid crystalline nanoparticles (BJO-DOX-LCNPs) were performed with the human breast cancer MCF-7 cells line and MCF-7 cells with doxorubicin resistance (MCF-7/DOX), respectively. The obtained pH-sensitive nanomedicines demonstrated enhanced anti-tumor efficacy. The performed preliminary studies suggested a potential reverse of the resistance of the MCF-7/DOX cells to DOX. These results highlighted the necessity of further understanding of the link between the established pH-dependent drug release profiles of the nanocarriers and the role of their pH-switchable inverted hexagonal, bicontinuous cubic, sponge or emulsified emulsion inner organizations for the therapeutic outcomes.

Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells

“…Nanoparticles are extensively inspected to prepare multifunctional smart materials [26][27][28][29][30] and are widely employed in various biomedical applications [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49].…”

Design and Characterization of Glyceryl Monooleate-Nanostructures Containing Doxorubicin Hydrochloride

“…Several GMO-based nanosystems used for the delivery of DOX [ 21 , 22 , 23 , 24 ] have been widely implemented and described in literature but in this experimental work, for the first time (to the best of our knowledge), a remote loading approach was used to enhance the entrapment efficiency of the drug, which is normally employed to achieve a high retention rate in liposomes [ 25 ]. The cytotoxicity of the nanosystems was also investigated on different breast cancer cell lines (MCF-7 and MDA-MB-231).…”

Microfluidic technologies for the synthesis and manipulation of biomimetic membranous nano-assemblies

“…Triggered release mechanisms of hexosomes tend to involve controlled phase transitions, stimulated by temperature changes and pH. 21,81,82 Techniques used in their formation mirror those used in cubosome assembly, including emulsification followed by solvent evaporation, and lipid film hydration with a secondary probe sonication or high shear homogenisation step. 21,83 Interestingly, microfluidic hydrodynamic flow focusing (MHF) has been used to successfully generate hexosomes of relatively narrow size distribution, although only one example exists to date (Fig.…”