Biomimetic Cationic Nanoparticles Based on Silica: Optimizing Bilayer Deposition from Lipid Films

Abstract

The optimization of bilayer coverage on particles is important for a variety of biomedical applications, such as drug, vaccine, and genetic material delivery. This work aims at optimizing the deposition of cationic bilayers on silica over a range of experimental conditions for the intervening medium and two different assemblies for the cationic lipid, namely, lipid films or pre-formed lipid bilayer fragments. The lipid adsorption on silica in situ over a range of added lipid concentrations was determined from elemental analysis of carbon, hydrogen, and nitrogen and related to the colloidal stability, sizing, zeta potential, and polydispersity of the silica/lipid nanoparticles. Superior bilayer deposition took place from lipid films, whereas adsorption from pre-formed bilayer fragments yielded limiting adsorption below the levels expected for bilayer adsorption.

Keywords: AEROSIL OX-50; N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride; cationic bilayer fragments; colloidal stability; dioctadecyldimethylammonium bromide; elemental analysis for in situ adsorption; films of cationic lipids; optimal bilayer adsorption from films.

Figure 1

Chemical structures for the cationic lipids and silica micrograph. (a) N-[1-(2,3-dioleoyloxypropyl)-N,N,N-trimethylammonium chloride (DOTAP) chemical structure. (b) Silica particles (AEROSIL OX-50) from transmission electron microscopy (TEM) as provided by the supplier. (c) Dioctadecyldimethylammonium bromide (DODAB) chemical structure.

Figure 2

Procedure for dispersing silica/cationic lipid from lipid films. The lipid employed was either DOTAP or DODAB. Vortexing was done at an arbitrary temperature of 56 °C, above the mean phase transition temperature of the DODAB or DOTAP bilayer.

Figure 3

Colloidal stability of silica/cationic lipid dispersions in 1 mM KCl solution over a range of DODAB or DOTAP concentrations at 2 mg/mL silica. DOTAP or DODAB concentrations were 0, 0.05, 0.1, 0.2, 0.3, 0.5, 0.6, and 1.0 mM. BF: Bilayer fragments.

Figure 4

Size distributions for two different but equivalent dispersions: (a) silica (2 mg/mL); (b) silica/DODAB from DODAB BF at 0.5 mM DODAB; (c) silica/DOTAP dispersions from DOTAP films at 0.5 mM DOTAP; (d) silica/DODAB from DODAB films at 0.5 mM DODAB. Silica and lipid interacted for 24 h in 1 mM KCl solution before taking the supernatants and diluting them by 1:20 for sizing. Dz: Z-average diameter.

Figure 5

Adsorption isotherms for DOTAP onto silica. (a) Adsorption isotherms for DOTAP onto silica from DOTAP films in pure water. (b) Adsorption isotherms for DOTAP onto silica from DOTAP films in 1 mM KCl. (c) Mean DOTAP adsorption onto silica from DOTAP films in water or in KCl 1 mM aqueous solution. (d) Cross-section of a silica NP covered by a DOTAP cationic bilayer. The dashed line at 0.266 mM DOTAP represents the theoretical concentration for bilayer adsorption. Silica concentration was 2 mg/mL. Each mean adsorption value and the respective mean standard deviation was obtained from at least two different determinations for each element.

Figure 6

Adsorption isotherms for DODAB onto silica. (a) DODAB adsorption onto silica (2 mg/mL) from DODAB films in pure water. (b) DODAB adsorption on to silica (2 mg/mL) from DODAB BF in pure water. (c) DODAB adsorption onto silica (2 mg/mL) from films in 1 mM KCl water solution. (d) DODAB adsorption onto silica (2 mg/mL) from DODAB BF in 1 mM KCl aqueous solution. The dashed line at 0.288 mM DODAB represents the theoretical concentration for bilayer adsorption. Each mean adsorption value and respective mean standard deviation was obtained from at least two different determinations for each element.

Figure 7

Adsorption isotherms for DODAB from films or BF onto silica. (a) Mean DODAB adsorption onto silica (2 mg/mL) from DODAB films. (b) Mean DODAB adsorption onto silica (2 mg/mL) from DODAB BF. The dashed line at 0.288 mM DODAB represents the theoretical concentration corresponding to bilayer adsorption. Each mean adsorption value and respective mean standard deviation was obtained from at least two different determinations for each element.