Enhancing the Solubility and Oral Bioavailability of Poorly Water-Soluble Drugs Using Monoolein Cubosomes

Abstract

Monoolein cubosomes containing either spironolactone (SPI) or nifedipine (NI) were prepared using a high-pressure homogenization technique and characterized in terms of their solubility and oral bioavailability. The mean particle size, polydispersity index (PDI), zeta potential, solubility and encapsulation efficiency (EE) values of the SPI-and NI-loaded cubosomes were determined to be 90.4 nm, 0.187, 13.4 mV, 163 µg/mL and 90.2%, and 91.3 nm, 0.168, 12.8 mV, 189 µg/mL and 93.0%, respectively, which were almost identical to those of the blank cubosome. Small-angle X-ray scattering analyses confirmed that the SPI-loaded, NIloaded and blank cubosomes existed in the cubic space group Im3 m. The lattice parameters of the SPI-and NI-loaded cubosomes were 147.6 and 151.6 Å, respectively, making them almost identical to that of blank cubosome (151.0 Å). The in vitro release profiles of the SPI-and NI-loaded cubosomes showed that they released less than 5% of the drugs into various media over 12-48 h, indicating that most of the drug remained encapsulated within the cubic phase of their lipid bilayer. Furthermore, the in vivo pharmacokinetic results suggested that these cubosomes led to a considerable increase in the systemic oral bioavailability of the drugs compared with pure dispersions of the same materials. Notably, the stability results indicated that the mean particle size and PDI values of these cubosomes were stable for at least 4 weeks. Taken together, these results demonstrate that monoolein cubosomes represent promising drug carriers for enhancing the solubility and oral bioavailability of poorly water-soluble drugs.Key words cubosome; drug carrier; monoolein; nifedipine; spironolactone; high-pressure homogenizationThe low oral bioavailability of poorly water-soluble drugs remains one of the most challenging aspects of drug development. A wide variety of formulation approaches, including lipid nanoparticles, solid dispersions, complexes with cyclodextrin or chitosan-alginates, nanoemulsions and liposomes, have been used to enhance the solubility and bioavailability of several poorly water-soluble drugs. [1][2][3][4][5] Cubosomes have recently attracted considerable interest from formulation scientists in terms of their potential application as drug delivery systems based on their highly ordered, compartmentalized internal structures, high lipid content and large surface area.Cubosomes are inverse bicontinuous cubic lyotropic crystalline nanoparticles that can be loaded with poorly water-soluble drugs in their three-dimensional cubic phases, leading to pronounced increases in the solubility, stability and bioavailability of these drugs.6-9) Cubosomes can be prepared using nontoxic, biocompatible and biodegradable ingredients, and can be readily used to encapsulate lipophilic drugs. Monoolein is a common amphiphilic building block for the preparation of cubosomes, 10) and is relatively cheap compared with other commonly used lipid excipients such as phytantriol. Nonionic triblock copolymer (Pluronic F-127) is ...

<p>AT101-Loaded Cubosomes as an Alternative for Improved Glioblastoma Therapy</p>

“…Moreover, when considering the delivery of hydrophobic drugs, such as AT101, the benefit of using cubosomes is the improvement in the bioavailability of the drug due to its greater solubility in the lipid membrane of formed nanoparticles and finally their dispersion in water-based media. A similar approach to enhancing the solubility and, hence, the bioavailability of hydrophobic drugs by using monoolein-and phytantriol-based cubosomes was described by Ali et al 50,51 The improved cytotoxicity response to GMO-AT101 cubosomes can be further related to the pronounced internalization associated with endocytic pathways, as reported previously by Abdel-Bar et al ( Figure 6). 47 Moreover, AT101 molecules exhibit a high binding affinity to proteins resulting in a reduced AT101 activity.…”

Nature‐Inspired Design and Application of Lipidic Lyotropic Liquid Crystals

“…Sustained release of caffeine may be useful to have alertness longer than the 3 or 4 h corresponding to immediate absorption. A consequence of the controlled release property is that lipidic lyotropic liquid crystalline phases can also be used for amphiphilic and lipophilic substances to increase bioavailability, which is the amount of an active substance, which reaches the plasma after transiting the digestive tract and being absorbed across the gastro‐intestinal barrier. For tocopherol vitamin, for instance, it was demonstrated that the L 1 phase, composed of micelles of positive curvature, made with polysorbate, leads to higher vitamin absorption than commercial soft gel capsules .…”

Role of nanostructures in improvising oral medicine

“…Studies have shown that GMO cubosomes improve the efficiency of AmB via the oral route [53]. On the other hand, monoolein cubosomes enhance the oral bioavailability and solubility of poorly water-soluble drugs [54]. Recent studies have been shown that cubosomes act as efficient oral drug delivery systems in enhancing the release of clopidogrel bisulphate in the intestine [55].…”