Cubic Phase Nanoparticles (Cubosome):  Principles for Controlling Size, Structure, and Stability

Abstract

Methods and compositions for producing lipid-based cubic phase nanoparticles were first discovered in the 1990s. Since then a number of studies have been presented, but little is known about how to control key properties such as particle size, morphology, and stability of cubic phase dispersions. In the present work we give examples of how these properties can be tuned by composition and processing conditions. Importantly we show that stable particle dispersions with consistent size and structure can be produced by a simple processing scheme comprising a homogenization and heat treatment step.

Self-Assembled Multicompartment Liquid Crystalline Lipid Carriers for Protein, Peptide, and Nucleic Acid Drug Delivery

“…19,[22][23][24]26,27 The mechanism of fragmentation of the bicontinuous cubic membranes has not been fully elucidated. The established procedures for cubosome production employ powerful energy techniques such as high shear homogenization by microfluidization, ultrasonication, and high-temperature treatment in an autoclave.…”

“…24 Nanoparticles with well-ordered internal cubic structure and periodic bilayer inner organization have been prepared upon heat treatment to a temperature that is above the cloud point of the stabilizing copolymer. 24 At ambient temperatures, the dispersed systems predominantly consist of coexisting cubic and vesicular particles. Cryo-TEM investigations have demonstrated 24 that the majority population of the nanoparticles has vesicle morphologies, which can fuse into nonequilibrium aggregates.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] The investigations, by means of time-resolved SAXS, of the dynamic topological transitions of selfassembled amphiphilic mixtures have allowed the discovery of lipid-based nanocarriers with tunable internal organizations and nanochannel sizes. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] The phase states of nonlamellar lipids, amphiphilic mixtures with lipopolymers or lipophilic conjugates, such as peptide surfactants, squalenoyl (SQ) derivatives, and acylated and peptidolipidyl-modified cyclodextrins, have been studied toward the design of novel controlled drug delivery nanocarriers with enhanced performance. In this Account, we discuss structural studies of lipid and lipid-polymer self-assemblies in aqueous phase that characterized the nanochannel network organization of amphiphilic vehicles for entrapment of proteins and peptides, as well as of DNA.…”

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“…The collected supernatant was then diluted appropriately and estimated using UV visible spectrophotometer at 228 nm. [7] The percent of encapsulation efficiency (EE %) was determined by the following equation:…”

“…Zeta potential of cubosomes: [7] The zeta potential of the cubosomes was determined using Zetasizer and the value of the cubosomes was found to be +43.6 mV which indicates that cubosomes were stable as shown in Figure 7. Figure 9 and10, the drug release was found to increase by increasing GMO concentration from 5 to 50 % (w/w), the lipid concentration was increased, drug release was increased but phase separation was observed as seen in the remaining formulations.…”