Surface active properties of lipid nanocapsules

RESEARCH ARTICLE Surface active properties of lipid nanocapsules Celia R. A. Mouzouvi1,2, Anita Umerska1*, André K. Bigot3, Patrick Saulnier1 1 ‘Micro et Nanomédecines biomimétiques—MINT‘, INSERM U1066 Université d’Angers, CNRS 6021, Université Bretagne Loire, Angers, France, 2 Laboratoire de Pharmacie Galenique et de technologie Pharmaceutique, UFR Pharmacie, FSS, Université d’Abomey-calavi, Cotonou, Benin, 3 Unité d’Immunologie, Faculté des Sciences de la Santé, Université d’Abomey-calavi, Cotonou, Benin * a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Mouzouvi CRA, Umerska A, Bigot AK, Saulnier P (2017) Surface active properties of lipid nanocapsules. PLoS ONE 12(8): e0179211. https:// doi.org/10.1371/journal.pone.0179211 Editor: Leonardo Fraceto, Universidade Estadual Paulista Julio de Mesquita Filho, BRAZIL Received: January 23, 2017 Accepted: May 25, 2017 Published: August 10, 2017 Copyright: © 2017 Mouzouvi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper. Funding: This study was funded by ‘Service de Cooperation et d’Action Culturelle’ of the French Embassy in Benin, by Z-cube (Italy) and by Ministère de l’Enseignement Superieur et de la Recherche Scientifique du Bénin. Competing interests: The authors have declared that no competing interests exist. Abstract Lipid nanocapsules (LNCs) are biomimetic nanocarriers used for the encapsulation of a broad variety of active ingredients. Similar to surface active compounds, LNCs contain both hydrophilic and hydrophobic parts in their structure. Moreover, the components of LNCs, macrogol 15 hydroxystearate (MHS) and lecithin, are known for their surface active properties. Therefore, the aim of this paper was to investigate the capability of the LNCs to decrease surface tension using two techniques: drop tensiometry and the Wilhelmy plate method. LNCs with diameters ranging from 30 to 100 nm were successfully obtained using a phase inversion technique. The LNCs’ properties, such as size and zeta potential, depend on the composition. LNCs exhibit a lower limiting surface tension compared to MHS (34.8–35.0 mN/m and 37.7– 38.8 mN/m, respectively), as confirmed by both drop tensiometry and the Wilhelmy plate method. LNCs have exhibited a saturated interfacial concentration (SIC) that was 10-fold higher than the critical micellar concentration (CMC) of MHS or the SIC of binary and ternary mixtures of LNC ingredients. The SIC of the LNC formulations depended on the mass mixing ratio of the MHS/triglycerides but not on the presence of lecithin. The CMC/SIC values measured by the Wilhelmy plate method were higher than those obtained using drop tensiometry because of the longer duration of the tensiometry measurement. In conclusion, the surfactantlike properties of the LNCs offer new possibilities for medical and pharmaceutical applications. Introduction Lipid nanocapsules (LNCs) are biomimetic nanocarriers with a structure that is a hybrid between polymeric nanoparticles and liposomes. LNCs contain an oily core composed of medium chain triglycerides surrounded by a surfactant shell made of a PEGylated surfactant and optionally lecithin or other co-surfactants [1,2]. All above-mentioned LNC components are approved by the FDA for oral, topical and parenteral administration [1]. Numerous active ingredients, mainly drugs with lipophilic properties, have already been incorporated into LNCs, including fluticasone propionate [3], essential oils: eugenol, carvacrol and trans-cinnamaldehyde [4], paclitaxel [5] and ibuprofen [6]. Recently, interest in the use LNCs as carriers for hydrophilic compounds (e.g., polymyxin B, calcitonin and antimicrobial peptides) using PLOS ONE | https://doi.org/10.1371/journal.pone.0179211 August 10, 2017 1 / 19 Surface active properties of lipid nanocapsules adsorption processes has been developed [2]. LNCs are carriers for various administration routes, including pulmonary [3,5], intravenous [7], oral and local delivery [8]. The advantages of LNCs include small particle size (20–100 nm), good physical stability (18 months) and manufacturability via a phase inversion temperature method, which is a low energy, organic solvent-free process [8,9]. Physical properties, such as particle size and zeta potential, and biological properties of the LNCs have extensively been studied since 2002 [3,8,10–13]. Although there have been reports on other LNC physical properties, such as elasticity [13], no study on the ability of LNCs to decrease surface tension has been performed to date. Surface tension is the elastic tendency of a fluid surface to acquire a minimum surface area. At a molecular level, this phenomenon results from the difference in energy between molecules at a fluid interface and in the bulk [14]. The interfacial/surface tension is fundamentally important to colloid science [14]. Advancements in surface chemistry have led to countless applications in several industries. For instance, interfaces are critically important in pharmaceutics, biotechnology and biomedicine [15]. In pharmaceutical sciences, interfacial phenomena play an important role in the processing of a variety of formulations. The interactions between particles and interfaces may occur during the processing (e.g., spray drying) or administration (e.g., nebulization). The subsequent behaviour of these formulations in vivo is often governed by an interfacial process. In biological environments, particles interact with various interfaces [16]. The surface activity of the LNCs may have an important influence on their interactions with membranes, including such phenomena as shape changes, vesiculation, membrane disruption and solubilisation. Many compounds, including pharmacologically active molecules, are amphiphilic—they bear a polar head group (either non-ionic or zwitterionic, anionic or cationic) and a hydrophobic portion [17]. In many ways, colloidal particles resemble surfactant molecules [18]. Although nanoparticles with a suitable size and surface chemistry may strongly adsorb at interfaces, there is an ongoing debate whether they can reduce the interfacial tension [18,19]. For instance, Okubo [20] showed that polystyrene particles, which yielded crystalline structures at the interface, were capable of reducing interfacial tension; however, silica particles, which were independent of the structure and polystyrene particles with non-yielding crystalline structures, did not affect the surface tension. Particles have been shown to act as stabilizers in many foam and emulsion systems (Pickering emulsions) and could prove economically attractive as replacements for conventional surfactants [21]. Similar to surface active compoun (...truncated)