Characterizing Lipid‐Coated Mesoporous Silica Nanoparticles as CD169‐Binding Delivery System for Rilpivirine and Cabotegravir

Abstract

Herein, lipid‐coated mesoporous silica nanoparticles (LMSNs) are investigated as biomimetic delivery vehicle for two antiretroviral (ARV) compounds, rilpivirine (RPV), and cabotegravir (CAB). Monosialodihexosylganglioside (GM3) is incorporated into the membrane to facilitate LMSN binding to CD169 (Siglec‐1)‐expressing myeloid cells, that are predominantly expressed in secondary lymphoid tissues in vivo. It is demonstrated that in addition to providing CD169‐binding functionalities, the lipid membrane around the silica core provides stealth properties that dampen the inflammatory cytokine response to ARVs‐loaded LMSN in human monocyte‐derived macrophages. Quantification of RPV and CAB releases from nanoparticles, and assessment of antiviral potency to human immunodeficiency virus 1 (HIV‐1) infection in vitro reveals that RPV and CAB co‐formulated into LMSN retain optimal antiviral potency for 90 days, even upon storage at room temperature, making LMSN an attractive nanoplatform, immune to cold chain requirements. These findings suggest that GM3–LMSN equip the mesoporous silica nanoparticle (MSN) core with lipid‐derived properties for surface passivation and lipid‐mediated binding that are of high interest for achieving an effective delivery of ARVs to tissue reservoirs of HIV‐1 replication.

Current status of silica-based nanoparticles as therapeutics and its potential as therapies against viruses

“…However, compared to LNP, silica has the added advantage of being structurally tunable; its physical characteristics such as its size ( Li et al, 2017 ) and internal nanonetwork structure ( Jadhav et al, 2015 ) can be precisely tuned in order to fulfil specific applications such as controlled release of its payload ( Prabhakar et al, 2016 ). These physical characteristics have been demonstrated to allow silica nanoparticles to deliver combinations of antiviral drugs, such as for the treatment of HIV in animal models ( Zang et al, 2022 ). Silica nanoparticles have also been used to create vaccines.…”

A Facile Method to Coat Nanoparticles with Lipid Bilayer Membrane: Hybrid Silica Nanoparticles Disguised as Biomembrane Vesicles by Particle Penetration of Concentrated Lipid Layers

“…[33] In addition, by loading the core nanoparticle with bioactive substances in advance, it is possible to load drugs inside lipid membranes with extremely high efficiency. [34,35] Lipid membrane-coated nanoparticles have various advantageous properties of the inorganic nanoparticle, such as chemical and optical properties, as well as those of the lipid membrane, such as biocompatibility and the ability to encapsulate drugs.…”