Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage

Abstract

Delayed cerebral vasospasm following subarachnoid hemorrhage causes severe ischemic neurologic deficits leading to permanent neurologic dysfunction or death. Reduced intravascular and perivascular nitric oxide (NO) availability is a primary pathophysiology of cerebral vasospasm. In this study, we evaluated NO-loaded echogenic liposomes (NO-ELIP) for ultrasound-facilitated NO delivery to produce vasodilation for treatment of vasospasm following subarachnoid hemorrhage. We investigated the vasodilative effects of NO released from NO-ELIP both ex vivo and in vivo. Liposomes containing phospholipids and cholesterol were prepared, and NO was encapsulated. The encapsulation and release of NO from NO-ELIP were determined by the syringe/vacuum method and ultrasound imaging. The ex vivo vasodilative effect of NO-ELIP was investigated using rabbit carotid arteries. Arterial vasodilation was clearly observed with NO-ELIP exposed to Doppler ultrasound whereas there was little vasodilative effect without exposure to Doppler ultrasound in the presence of red blood cells. Penetration of NO into the arterial wall was determined by fluorescent microscopy. The vasodilative effects of intravenously administered NO-ELIP in vivo were determined in a rat subarachnoid hemorrhage model. NO-ELIP with ultrasound activation over the carotid artery demonstrated effective arterial vasodilation in vivo resulting in improved neurologic function. This novel methodology for ultrasound-controlled delivery of NO has the potential for therapeutic treatment of vasospasm following subarachnoid hemorrhage. This ultrasound-controlled release strategy provides a new avenue for targeted bioactive gas and therapeutic delivery for improved stroke treatment.

Near-infrared fluorescence imaging-guided focused ultrasound-mediated therapy against Rheumatoid Arthritis by MTX-ICG-loaded iRGD-modified echogenic liposomes

“…In contrast, low-frequency ultrasound is a highly effective and relatively safe trigger for controlled drug release from nanoparticles. Kim et al fabricated nitric oxide (NO)-loaded nanoparticles that released the gas at the subarachnoid hemorrhage lesions upon ultrasonic stimulation to therapeutically effective levels 13 .…”

The Role of Nanomaterials in Stroke Treatment: Targeting Oxidative Stress

“…They can also be modified with ligands for receptor targeting, such as transferrin, and this leads to enhanced translocation across the BBB [ 48 ]. Additionally, echogenic liposomes (ELIP) can be guided by ultrasound to the target site [ 49 ].…”

“…Nanoceria were modified with aminocaproic acid and PEG, which reduced the apoptosis of macrophages and accumulation in the ipsilateral cerebral hemisphere where the aneurysm was ruptured [ 38 ]. Meanwhile, curcumin, encapsulated in PLGA nanoparticles and NO-loaded ELIP (NO-ELIP), extenuates EBI [ 49 , 107 ]. Aneurysmal repair essentially functions as a prophylactic for future hemorrhages, and platinum coils are used in clinical practice.…”

Increasing Doxorubicin Loading in Lipid-Shelled Perfluoropropane Nanobubbles via a Simple Deprotonation Strategy

“…Among these, US is considered as an ideal modality for this purpose because it is widely available, relatively inexpensive, safe from hazardous ionizing radiation, and is a non-invasive module for simultaneous real-time imaging and triggering release from vehicle (Böhmer et al, 2009;Deckers and Moonen, 2010;Zhu et al, 2016). A variety of drug-loaded nanoparticles (NPs) such as liposomes or micelles in combination with therapeutic agents have been used in USmediated drug delivery approach (Husseini et al, 2002;Pruitt and Pitt, 2002;Kim et al, 2013). However, the clinical application of NPs is limited due to their corresponding high resonant frequency which does not allow them to be easily be visible on clinical US.…”