Cubic-to-inverted micellar and the cubic-to-hexagonal-to-micellar transitions on phytantriol-based cubosomes induced by
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ORIGINAL ARTICLE
Cubic-to-inverted micellar and the cubic-to-hexagonal-to-micellar transitions on phytantriol-based cubosomes induced by solvents Mayra C. G. Lotierzo 1 & Bruna R. Casadei 2 Leandro R. S. Barbosa 1,2
&
Raphael Dias de Castro 1,2
&
Barbara Malheiros 1
&
# Controlled Release Society 2020
Abstract Cubosomes are nanoparticles composed of a specific combination of some types of amphiphilic molecules like lipids, such as phytantriol (PHY), and a nonionic polymer, like poloxamer (F127). Cubosomes have a high hydrophobic volume (> 50%) and are good candidates for drug delivery systems. Due to their unique structure, these nanoparticles possess the ability to incorporate highly hydrophobic drugs. A challenge for the encapsulation of hydrophobic molecules is the use of organic solvents in the sample preparation process. In this study, we investigated the structural influence of four different solvents (acetone, ethanol, chloroform, and octane), by means of small-angle X-ray scattering and cryogenic electron microscopy techniques. In the presence of a high amount of acetone and ethanol (1:5 solvent:PHY volumetric ratio), for instance, a cubic-to-micellar phase transition was observed due to the high presence of these two solvents. Chloroform and octane have different effects over PHYbased cubosomes as compared to acetone and ethanol, both of them induced a cubic-to-inverse hexagonal phase transition. Those effects are attributed to the insertion of the solvent in the hydrophobic region of the cubosomes, increasing its volume and inducing such transition. Moreover, a second phase transition from reversed hexagonal-to-inverted micellar was observed for chloroform and octane. The data also suggest that after 24 h of solvent/cubosome incubation, some structural features of cubosomes change as compared to the freshly prepared samples. This study could shed light on drug delivery systems using PHY-based cubosomes to choose the appropriate solvent in order to load the drug into the cubosome. Keywords Cubosomes . SAXS . Solvents . Organic solvents . Cryo-TEM . Nanoparticles . Phytantriol . Phase diagram . Effects of solvents in nanoparticles
Abbreviations Act Acetone Clf Chloroform Cryo-TEM Cryogenic electron microscopy DH Hydrodynamic diameter DLS Dynamic light scattering EtOH Ethanol F127 Pluronic F-127 LogP Octanol/water partition coefficient
* Leandro R. S. Barbosa [email protected] 1
Department of Biochemical and Pharmaceutical Technology, University of São Paulo, Av. Prof. Lineu Prestes n 580 Bloco 16, São Paulo, SP 05508-000, Brazil
2
Institute of Physics, University of São Paulo, Rua do Matão, 1371, São Paulo 05508-090, Brazil
Oct PHY PHY-CUB SAXS Tm
Octane Phytantriol Cubosome-based phytantriol Small-angle X-ray scattering Melting temperature
Introduction Cubosomes are nanoparticles composed of lyotropic liquid crystals that present cubic inner structures [1]. The most common symmetries found in the cubosomes are the cubic bicontinuous Ia3d, Pn3m, and Im3m [2]. Generally, assigned via small-a
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