Targeted Propolis-Loaded Poly (Butyl) Cyanoacrylate Nanoparticles: An Alternative Drug Delivery Tool for the Treatment of Cryptococcal Meningitis

Abstract

In this study, we describe a nano-carrier system for propolis that is able to cross an in vitro model of the blood-brain barrier (BBB) and effectively reduce the virulence of Cryptococcus neoformans in animal models. Antimicrobial properties of propolis have been widely studied. However, propolis applications are limited by its low water solubility and poor bioavailability. Therefore, we recently formulated novel poly (n-butyl cyanoacrylate) nanoparticles (PBCA-NP) containing propolis. PBCA-NP are biocompatible, biodegradable and have been shown to effectively cross the BBB using apolipoprotein E (ApoE) as a ligand. Prepared nanoparticles were characterized for particle size, zeta potential, propolis entrapment efficiency and in vitro release. Additionally, the PBCA-NP were functionalized with polysorbate 80, which then specifically adsorbs ApoE. Using an in vitro BBB model of human brain microvascular endothelial cells hCMEC/D3, it was shown that fluorescence labelled ApoE-functionalized PBCA-NP were internalized by the cells and translocated across the cell monolayer. Propolis-loaded PBCA-NP had in vitro, antifungal activity against C. neoformans, which causes meningitis. To utilize the invertebrate model, Galleria mellonella larvae were infected with C. neoformans and treated with propolis-loaded PBCA-NP. The larvae exhibited normal behavior in toxicity testing, and treatment with propolis-loaded PBCA-NP increased survival in the C. neoformans-infected larvae group. In addition, following cryptococcal infection and then 7 days of treatment, the tissue fungal burden of mice treated with propolis-loaded PBCA-NP was significantly lower than control groups. Therefore, our ApoE-functionalized propolis-loaded PBCA-NP can be deemed as a potential targeted nanoparticle in the therapeutic treatment of cerebral cryptococcosis.

Molecular Nanoparticles of Ferric–Tannic Complexes Enhance Brain Magnetic Resonance Imaging and Activate Brain Clearance Pathways

“…The hCMEC/D3 cells were cultured on transwell inserts (24-well, 0.4 μm pore size, Millipore), precoated with collagen type I (1 × 10 5 cells cm –2 ), in the culture medium. The cells were left to grow until they had reached 70–80% confluency, which was confirmed by a transepithelial/transendothelial electrical resistance (TEER) measurement (EVOM2) of 50–60 ohm cm –2 . , Subsequently, the culture medium of the upper compartment was replaced with a fresh medium containing FTs (with and without CsA), while the culture medium of the lower chamber was replaced with a fresh culture medium without FTs. The cells were incubated for another 24 h. At different times of incubation, the culture medium was collected for iron quantification by ICP-OES.…”

Modulation of engineered nanomaterial interactions with organ barriers for enhanced drug transport

“…Other administration routes for brain delivery include delivery by the lymphatic system, which has been shown to be more effective than iv administration, 278 and oral delivery, which is often considered the most convenient administration route, because of the ease of administration and patient compliance. However oral delivery requires formulations to cross both the intestinal barrier and the BBB to reach the brain.…”

From propolis to nanopropolis: An exemplary journey and a paradigm shift of a resinous substance produced by bees

“…Similarly, the poly( n ‐butyl cyanoacrylate) nanoparticles (PBCA‐NPs) containing propolis were prepared, which were biocompatible, biodegradable, and were shown to effectively cross the blood–brain barrier and can be used for the treatment of cryptococcal meningitis (Thammasit et al, 2021). These nanoparticulate systems offer various advantages, including easy fabrication, versatile functionalization, and high entrapment efficiencies for poorly soluble compounds (Graf, McDowell, & Rades, 2009).…”