Glucan Particles for Macrophage Targeted Delivery of Nanoparticles

Abstract

Glucan particles (GPs) are hollow, porous 2–4 μm microspheres derived from the cell walls of Baker's yeast (Saccharomyces cerevisiae). The 1,3-β-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. GPs have been used for macrophage-targeted delivery of soluble payloads (DNA, siRNA, protein, and small molecules) encapsulated inside the hollow GPs via core polyplex and layer-by-layer (LbL) synthetic strategies. In this communication, we report the incorporation of nanoparticles as cores inside GPs (GP-NP) or electrostatically bound to the surface of chemically derivatized GPs (NP-GP). GP nanoparticle formulations benefit from the drug encapsulation properties of NPs and the macrophage-targeting properties of GPs. GP nanoparticle formulations were synthesized using fluorescent anionic polystyrene nanoparticles allowing visualization and quantitation of NP binding and encapsulation. Mesoporous silica nanoparticles (MSNs) containing the chemotherapeutic doxorubicin (Dox) were bound to cationic GPs. Dox-MSN-GPs efficiently delivered Dox into GP phagocytic cells resulting in enhanced Dox-mediated growth arrest.

Recent advances in oral vaccine development

“…93,94,[98][99][100][101][102][103] Based on the in situ layer-by-layer synthesis through electrostatic interactions, the group of Soto initially engineered yeast cell wall particles for DNA delivery. 104 This encapsulation strategy enables a high nucleic acid capacity and delivery, in addition to the oral bioavailability of β-glucan particles and their inherent β-glucan receptor targeting capacity toward APCs.…”

Molecular Concepts of Macrophage Targeting

“…For the purpose of macrophage targeting through β-glucan receptors, glucan particles (GPs) derived from the cell walls of baker's yeast (Saccharomyces cerevisiae) have been proposed as drug carriers [47][48][49][50]. GPs are hollow, porous 2-4 μm microspheres that can incorporate insoluble preformed nanoparticles as inside cores or drug-containing nanoparticles can be electrostatically bound to the surface of derivatized GPs [50].…”

“…GPs are hollow, porous 2-4 μm microspheres that can incorporate insoluble preformed nanoparticles as inside cores or drug-containing nanoparticles can be electrostatically bound to the surface of derivatized GPs [50]. As well, loading of soluble drugs inside GPs can be accomplished by incubating GPs with a soluble drug solution in a volume just suffi cient to swell the GPs (hydrodynamic volume) with subsequent encapsulation of the drug molecules inside the GPs by physical or chemical trapping [49].…”

1,3-Beta-Glucans: Drug Delivery and Pharmacology

“…Glucan microspheres are derived from the cell walls of Sacchamoryces cerevisiae (Baker's yeast) and are 2-4 µm in size. These are porous and hollow microparticles composed mainly of 1,3--D-glucan and small quantities of chitin [39]. The -glucan on the microspheres serves as a specific target for uptake by immune cells such as macrophages and dendritic cells [40].…”

“…The -glucan on the microspheres serves as a specific target for uptake by immune cells such as macrophages and dendritic cells [40]. Glucan microspheres can be used for delivering various payloads such as proteins [19], DNA [40], siRNA [16,41] and small molecules [39]. Typically small molecules are not easily entrapped within these glucan microspheres and hence the use of nanoparticles is necessary.…”