Overcoming Endocytosis Deficiency by Cubosome Nanocarriers

Abstract

The use of lipid-based nanoparticles for the delivery of biomacromolecules has attracted considerable attention due to the current interest in protein-based therapeutics. Cubosomes protect the incorporated therapeutics, which are susceptible to degradation by enzymes, thereby improving their bioavailability, and concomitantly enhance cellular uptake. The cubosome nanoparticles presented herein were loaded with bovine serum albumin (BSA) and characterized by small-angle X-ray scattering and dynamic light scattering techniques, while the BSA encapsulation and its release were evaluated in vitro. The ability of this formulation to increase the cellular uptake of albumin by 2-fold was tested on various types of renal tubular cells and confirmed by in vivo renal uptake experiments in mice. The obtained results show that cubosomes are able to deliver BSA inside the cell through distinct uptake and intracellular routing. These data were substantiated, with evidence of a high cubosome-mediated uptake of BSA in Clcn5 knockout mice characterized by defective receptor-mediated endocytosis. The use of cubosomes as a delivery system thus represents a promising approach to overcome the low endocytic uptake in diseased epithelial cells and to treat dysfunctions of the kidney proximal tubule.

Uptake Dynamics of Cubosome Nanocarriers at Bacterial Surfaces and the Routes for Cargo Internalization

“…The innate complexity of the cell wall is largely responsible for difficulties in the development of effective antibiotics. At the same time, cubic phase lipid NCs, i.e., cubosomes, have shown promise to deliver therapeutics to mammalian cell lines by means other than endocytosis; − one avenue is via lipid fusion of the cell membrane and nanoparticle. , These two points naturally lead to the question of how the uptake of these fusogenic NCs occurs in bacterial cells and, particularly for Gram-negative bacteria, if fusogenic NCs may circumvent resistance conveyed by the membrane.…”

In Vitro and In Vivo Toxicity and Biodistribution of Paclitaxel-Loaded Cubosomes as a Drug Delivery Nanocarrier: A Case Study Using an A431 Skin Cancer Xenograft Model

“…A plethora of studies have demonstrated the advantages of cubosomes as drug delivery nanocarriers, including the ability to encapsulate soluble, insoluble, and biomolecular therapeutics (such as proteins, small interfering RNAs, and plasmid DNAs) at high capacity, − the controlled release of encapsulated cargos via pH, and temperature-induced responsiveness, − as well as facilitated cellular uptake. − There are several recent reviews summarizing the vast literature on lipid-based cubosomes since their discovery four decades ago, , with focus on material design principles, , structural characterization techniques, − in vitro interactions, in vivo behaviors and performance as drug delivery systems, and various biomedical and industrial applications. ,− For example, cubosomes have been exploited to encapsulate a variety of chemotherapeutic drugs, including docetaxel, ,, elesclomol, paclitaxel (PTX), 5-fluorouracil, cisplatin, , curcumin, doxorubicin, , etoposide, and camptothecin, and tested for anticancer efficacies of these drug nanocarriers in various cell lines and disease models. In addition, the formulation process of cubosomes based on their self-assembly behavior is simple and quick, offering the potential of large-scale production for clinical translation .…”

Lipid Cubic Systems for Sustained and Controlled Delivery of Antihistamine Drugs

“…When nanoparticles interact and adsorb onto the cell membrane, changes in the zeta potential are seen as the adsorption of ions surrounding their surface, and the surfaces of the hydrodynamic shear and particle mobility are altered . An uptake through the cell’s plasma membrane after an adsorption can occur by means of different mechanisms including phago- or endocytosis. , Endocytosis is the process commonly observed in the internalization of nanoparticles, soluble molecules, proteins, and lipids − and is an energy-dependent process. ,, The mechanism may be either nonspecific or receptor-mediated and has been widely described in the uptake of cubosomes. − After the 12 h exposure to the cubosomes, the zeta potential returned to a more negative value and approached that of the untreated cells, suggesting that the adsorbed cubosomes could have been taken up by the cells after this time. The different cubosome samples exhibited different zeta potentials on their surfaces, from 0.97 ± 0.05 mV for the blank samples to 17.40 ± 0.01 mV with the AZL loaded samples, Table .…”