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Cubic-to-inverted micellar and the cubic-to-hexagonal-to-micellar transitions on phytantriol-based cubosomes induced by solvents

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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 PHY-based 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.

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Abbreviations

Act:

Acetone

Clf:

Chloroform

Cryo-TEM:

Cryogenic electron microscopy

D H :

Hydrodynamic diameter

DLS:

Dynamic light scattering

EtOH:

Ethanol

F127:

Pluronic F-127

LogP:

Octanol/water partition coefficient

Oct:

Octane

PHY:

Phytantriol

PHY-CUB:

Cubosome-based phytantriol

SAXS:

Small-angle X-ray scattering

Tm:

Melting temperature

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Acknowledgments

A special thanks to the National Laboratory of Synchrotron Light (LNLS), SAXS-1 beamline, and National Laboratory of Nanotechnology (LNNano), Campinas-SP, for the usage of their facilities.

Funding

Financial support for this research was provided by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (2015/15822-1), and CNPq (155970/2018-6, 308692/2018-7, 420567/2016-0) are also acknowledged. BRC, BM, and LRSB thank CNPq and ML thanks CAPES for research grant.

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Authors and Affiliations

  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

    Mayra C. G. Lotierzo, Raphael Dias de Castro, Barbara Malheiros & Leandro R. S. Barbosa

  2. Institute of Physics, University of São Paulo, Rua do Matão, 1371, São Paulo, 05508-090, Brazil

    Bruna R. Casadei, Raphael Dias de Castro & Leandro R. S. Barbosa

Authors
  1. Mayra C. G. Lotierzo
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  2. Bruna R. Casadei
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  3. Raphael Dias de Castro
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  4. Barbara Malheiros
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  5. Leandro R. S. Barbosa
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Correspondence to Leandro R. S. Barbosa.

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Lotierzo, M.C., Casadei, B.R., de Castro, R.D. et al. Cubic-to-inverted micellar and the cubic-to-hexagonal-to-micellar transitions on phytantriol-based cubosomes induced by solvents. Drug Deliv. and Transl. Res. 10, 1571–1583 (2020). https://doi.org/10.1007/s13346-020-00828-y

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