Low-energy nano-emulsification approach as a simple strategy to prepare positively charged ethylcellulose nanoparticles

Abstract

16Positively charged ethylcelulose nanoparticles have been obtained from 17 alkylamidoammonium/Span 80 based nano-emulsion templates. Oil-in-water 18 polymeric nano-emulsions form in a broad range of oil-to-surfactant ratios and water 19 contents above 75 wt% by a low-energy method at 25ºC. Nano-emulsions with a 20 water content of 90 wt% showed droplet sizes typically below 300 nm and high 21 positive zeta potential values (~55 mV). If oleylamine is added to the system, smaller 22 droplet sizes and higher zeta potential values (~66 mV) are obtained, but the stability 23 of the nano-emulsions decreases. Although these nano-emulsions are destabilized 24 by creaming, the period of stability is large enough to allow nanoparticle preparation 25 by solvent evaporation. Polymeric nanoparticles obtained show a globular core-shell-26 like morphology, with mean diameters of around 250 nm. The surface charge of the 27 nanoparticles is similar to that of the nano-emulsion template and remains positive 28 after 24 hours dialysis, suggesting slow desorption kinetics of the 29 alkylamidoammonium from the nanoparticle surface. These results indicate that the 30 proposed nano-emulsion approach is a good strategy for the preparation of positively 31 charged nanoparticles from nonionic ethylcellulose polymers. 32 33 KEYWORDS 35 Cationic nano-emulsion; ethylcellulose nanoparticles; cationic nanoparticles; low-36 energy emulsifiaction 37 38 surface. This has been shown with polar molecules, such as PEG derivatives [10], 59 polysorbate 80 [11] or chitosan [12], which are usually added in a late step, after 60 nanoparticle preparation as an alternative to covalent linking. 61 62 A well-known method for nanoparticle preparation is nano-emulsion templating. The 63 preparation of nano-emulsions by low-energy methods is convenient because it 64 allows achieving smaller and more homogeneous droplet sizes than high energy 65 emulsification methods. Although the preparation of O/W nano-emulsions with 66 nonionic surfactants by low-energy emulsification methods has widely been studied alkylamidoammonium derivatives are a class of cationic surfactants which in spite of 95 their frequent use in the home and personal-care industry have not been explored yet, 96to our best knowledge, for biomedical applications. In contrast to their amidoamine 97 counterparts, they have the advantage of being permanently positively charged, 98 regardless of the pH of the dispersing medium, due to the quaternized ammonium 99 end group. In this paper we propose the preparation of positively charged 100 nanoparticles from ethylcellulose nano-emulsion templates formed in a mixed 101 cationic/nonionic surfactant system. The purpose of this paper is to explore the 102 4 feasibility of endowing positive surface charge to ethylcellulose nanoparticles 103 prepared by a low-energy emulsification-solvent evaporation method, by using a 104 cationic alkylamidoammonium surfactant to modulate the surface charge of the 105 nanoparticles, and assess its permanence when exposed to...

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“…As shown in Figure 2b, the nano-emulsions formed display typically a translucent to transparent appearance, depending on the O/S ratio and the HEPES 20 mM content, with a bluish shine due to the Tyndall effect. This appearance is strikingly different from previously reported systems prepared with the same cationic surfactant (CatA) but different nonionic surfactants (namely Span 80 and Cremophor WO7) which showed higher opacity (Leitner et al 2019;Calderó et al 2019). It is also worth mentioning that in the system described herein, the nano-emulsion domain is considerably larger than in the latter mentioned systems.…”

“…It is worth mentioning that HEPES solution contains zwitterionic molecules. The conductivity values attained, as well as the conductivity variation as a function of the aqueous component content are comparable to those obtained with similar systems described earlier, containing the same cationic surfactant but different nonionic surfactants, namely Span 80 (Leitner et al 2019) and Cremophor WO7 (Calderó et al 2019). Phase inversion takes place at about 25 wt% HEPES solution.…”

“…ETHOCEL is a trademark of the Dow Chemical Company). Ethoxyl content was 48.7% and the weightaverage molecular weight (Mw) was 66385 ± 322 Dalton with a polydispersity of 4.3 as determined by Gel Permeation Chromatography (Leitner et al 2019).…”

“…As for bottom-up techniques, the low-energy emulsification approach is an environmentally friendly method, which has been reported for the preparation of ethylcellulose nanoparticles (Spernarth et al 2007;Generalova et al 2009;Calderó et al 2011). Although ethylcellulose is nonionic, recently it has been shown that positively charged ethylcellulose nanoparticle dispersions can be obtained through nano-emulsion templating in cationic:non-ionic surfactant-based systems (Leitner et al 2019;Calderó et al 2019). These oil-in-water (O/W) nano-emulsion templates are obtained by a low-energy method and the positive surface charge of the dispersed systems is attributed to the cationic surfactant.…”

Ethylcellulose nanoparticles prepared from nano-emulsion templates as new folate binding haemocompatible platforms

“…Ethylcellulose nanoparticles show a negative surface charge when prepared with non-ionic ethoxylated surfactants by this approach [8,13]. However, it has been recently demonstrated that they can be endowed with a positive surface charge by using a surfactant mixture including a cationic amphiphilic molecule [12,14]. Positive surface charge of nanoparticles can be exploited to enhance cell uptake [15]; to promote adsorption to negatively charged surfaces [16]; to bind electrostatically molecules such as nucleic acids, drugs, inorganic nanoparticles, biomolecules [17], etc.…”