Liposome-Templated Supramolecular Assembly of Responsive Alginate Nanogels

Abstract

Nanosized gel particles (nanogels) are of interest for a variety of applications, including drug delivery and single-molecule encapsulation. Here, we employ the cores of nanoscale liposomes as reaction vessels to template the assembly of calcium alginate nanogels. For our experiments, a liposome formulation with a high bilayer melting temperature (Tm) is selected, and sodium alginate is encapsulated in the liposomal core. The liposomes are then placed in an aqueous buffer containing calcium chloride, and the temperature is raised up to Tm. This allows permeation of Ca2+ ions through the bilayer and into the core, whereupon these ions gel the encapsulated alginate. Subsequently, the lipid bilayer covering the gelled core is removed by the addition of a detergent. The resulting alginate nanogels have a size distribution consistent with that of the template liposomes (ca. 120-200 nm), as confirmed by transmission electron microscopy and light scattering. Nanogels of different average sizes can be synthesized by varying the template dimensions, and the gel size can be further tuned after synthesis by the addition of monovalent salt to the solution.

Liposomes in tissue engineering and regenerative medicine

“…The diffusion of calcium into the liposome interior resulted in alginate gelation within the liposome of size 748 + 280 nm [197]. Another study reported the production of alginate nanogels with a size distribution between 120 and 200 nm [196]. Liposomes were also used as a template to prepare monodisperse PEG hydrogel nanoparticles [20].…”

“…However, liposomes can be used as templates to produce polymeric nanoparticles and nanogels (figure 12) [20,196,197]. In this approach, the inner compartment of the liposome can be used as the reaction vessel [15,196]. For example, the encapsulation of sodium alginate was performed by the thin-film method.…”

Alginate Particles as Platform for Drug Delivery by the Oral Route: State-of-the-Art

“…For example, Haidar and coworkers produced core-shell hybrid nanoparticles by the layer-by-layer assembly of ALG and chitosan on liposomes for the delivery of a growth factor [155]. Conversely, Hong and collaborators used the core of liposomes with a high bilayer melting temperature as reaction vessels to template the assembly of ALG [156]. In this context, ALG was encapsulated in the liposomal core and exposed to a calcium chloride solution at a temperature above the melting point of the bilayer.…”

“…Then, the liposome was removed with surfactants to give place to 120–200 nm nanoparticles ALG. The process is presented in Figure 14 [156]. As mentioned above, pure drug crystals could also be used to assemble polyelectrolyte layers.…”

Characterization of liposomes with different intraliposomal viscosities

“…4 The intraliposomal aqueous core was gelated by crosslinking of hydrogel polymers for sustained release of the drug. 5,6 However, there has been no systematic study of the effect of intraliposomal viscosity on the flexibility of the lipid vesicle, transfer of molecules through the lipid membrane, and stability of liposomes as a function of the viscosity of the aqueous core of the liposomes. In this study, liposomes with different intraliposomal viscosities were systematically observed to evaluate intraliposomal viscosity as a means to enhance the stability of liposomes and to control the release rate of drugs from liposomes.…”