Intranasal Delivery of Liposomes to Glioblastoma by Photostimulation of the Lymphatic System

Abstract

The blood–brain barrier (BBB) limits the delivery of majority of cancer drugs and thereby complicates brain tumor treatment. The nasal-brain-lymphatic system is discussed as a pathway for brain drug delivery overcoming the BBB. However, in most cases, this method is not sufficient to achieve a therapeutic effect due to brain drug delivery in a short distance. Therefore, it is necessary to develop technologies to overcome the obstacles facing nose-to-brain delivery of promising pharmaceuticals. In this study, we clearly demonstrate intranasal delivery of liposomes to the mouse brain reaching glioblastoma (GBM). In the experiments with ablation of the meningeal lymphatic network, we report an important role of meningeal pathway for intranasal delivery of liposomes to the brain. Our data revealed that GBM is characterized by a dramatic reduction of intranasal delivery of liposomes to the brain that was significantly improved by near-infrared (1267 nm) photostimulation of the lymphatic vessels in the area of the cribriform plate and the meninges. These results open new perspectives for non-invasive improvement of efficiency of intranasal delivery of cancer drugs to the brain tissues using nanocarriers and near-infrared laser-based therapeutic devices, which are commercially available and widely used in clinical practice.

Early investigation of a novel SI306 theranostic prodrug for glioblastoma treatment

“…Compared to alternative administration methods, IN delivery has several advantages: it is comparatively noninvasive, avoids first‐pass metabolism, increases patient compliance, and minimizes side effects, considering that the healthy organs are not exposed to the therapeutic compound (Veronesi et al, 2020). In addition, the development of IN DDSs such as liposomes to increase aqueous solubility and permeability has already demonstrated a reduction in drug toxicity, and enhancement in pharmacokinetic properties by improving the physiochemical properties of the studied compounds (Semyachkina‐Glushkovskaya et al, 2022). Taking these data into account, new IN DDSs will be investigated and developed to overcome the ADME properties issues of ProSI‐DOTA( 68 Ga) 1 , and to evaluate its in vivo pharmacokinetic profile, paving the way for its future development.…”

Research progress in brain-targeted nasal drug delivery

“…Lipid-soluble compounds can be embedded in phospholipid bilayer membranes, whereas water-soluble compounds can be encapsulated in hydrophilic parts; therefore, liposomes can carry both lipid- and water-soluble drugs ( Duong et al, 2023 ). Owing to their surface charge, liposomes increase the contact time with the mucosa and improve the bioavailability of drugs while also protecting encapsulated biomolecules from degradation by enzymes in the nasal mucosa ( Semyachkina-Glushkovskaya et al, 2022 ). Liposomes cause only slight or no damage to the nasal mucosa, without inducing irritation or ciliary toxicity, and they are suitable for long-term administration ( Semyachkina-Glushkovskaya et al, 2022 ).…”

Low-Level Laser Treatment Induces the Blood-Brain Barrier Opening and the Brain Drainage System Activation: Delivery of Liposomes into Mouse Glioblastoma

“…The number of the GBM cells was counted on the TC20 Bio-Rad automatic cell counter (Bio-Rad, Moscow, Russia), and the viability analysis was determined using a trypan blue dye. The mouse EPNT-5 of GBM cells were transfected with pTagRFP-C DNA plasmid using the published method of liposomal transfection [ 57 , 58 ] followed by selection using geneticin (G418 antibiotic, neomycin analog). The resulting cell line EPNT-5-TagRFP has stable cultural and morphological characteristics.…”