Anti-transferrin receptor-modified amphotericin B-loaded PLA–PEG nanoparticles cure Candidal meningitis and reduce drug toxicity

Abstract

Fatal fungal infections in central nervous system (CNS) can occur through hematogenous spread or direct extension. At present, hydrophobic amphotericin B (AMB) is the most effective antifungal drug in clinical trials. However, AMB is hydrophobic and therefore penetrates poorly into the CNS, and therapeutic levels of AMB are hard to achieve. The transferrin receptor (TfR/CD71) located at the blood–brain barrier mediates transferrin transcytosis. In order to enhance the receptor-mediated delivery of AMB into CNS with therapeutic level, an anti-TfR antibody (OX26)-modified AMB-loaded PLA (poly[lactic acid])–PEG (polyethylene glycol)-based micellar drug delivery system was constructed. The prepared OX26-modified AMB-loaded nanoparticles (OX26-AMB-NPs) showed significant reduction of CNS fungal burden and an increase of mouse survival time. In conclusion, OX26-AMB-NPs represent a promising novel drug delivery system for intracerebral fungal infection.

Enhanced Killing and Antibiofilm Activity of Encapsulated Cinnamaldehyde against Candida albicans

“…To date, several antifungal ( Leal et al, 2015 ) and antibacterial ( Gubernator et al, 2007 ) drugs have been given as encapsulated liposomal formulations to enhance their therapeutic index. In particular, Amp B has been studied exclusively with the aim to reduce its toxicity and side-effects by entrapping into lipid complex and multilamellar (ML) vesicles ( Tang et al, 2015 ). The outermost bilayer of multilamellar phospholipid vesicles fuses with the plasma membrane of the cell, providing increased surface area and invagination of the excess plasma membrane ( Batzri and Korn, 1975 ).…”

Key for crossing the BBB with nanoparticles: the rational design

“…However, these nanoparticles have to face competition with the endogenous ligands of these receptors. This problem can be avoided by using antibodies against transferrin receptors, i.e., OX26, which bind to another binding site of the receptor [74, [80][81][82][83]. However, it has been shown that OX26 is mostly associated with brain capillaries through the brain parenchyma [117].…”

Development and evaluation of novel tumor-targeting paclitaxel-loaded nano-carriers for ovarian cancer treatment: in vitro and in vivo

“…Polylactic acid (PLA) is a synthetic biodegradable polymer that has been approved by the U.S. Food and Drug Administration (FDA) for medical applications [18, 19]. However, because of its weak hydrophilicity, excessively long degradation time, and low drug loading of polar drugs [20, 21], PLA’s applications are limited. To overcome these shortcomings, PEG was combined with PLA to form a block co-polymer in this study [22–24].…”