Traumatic brain injury opens blood–brain barrier to stealth liposomes via an enhanced permeability and retention (EPR)-like effect

Abstract

The opening of the tight junctions in the blood-brain barrier (BBB) following traumatic brain injury (TBI) is hypothesized to be sufficient to enable accumulation of large drug carriers, such as stealth liposomes, in a similar manner to the extravasation seen in tumor tissue via the enhanced permeability and retention (EPR) effect. The controlled cortical impact model of TBI was used to evaluate liposome accumulation in mice. Dual-radiolabeled PEGylated liposomes were administered either immediately after induction of TBI or at increasing times post-TBI to mimic the likely clinical scenario. The accumulation of radiolabel in the brain tissue ipsilateral and contralateral to the site of trauma, as well as in other organs, was evaluated. Selective influx of liposomes occurred at 0-8 h after injury, while the barrier closed between 8 and 24 hr after injury, consistent with reports on albumin infiltration. Significantly enhanced accumulation of liposomes occurred in mice subjected to TBI compared to anaesthetized controls, and accumulation was greater in the injured versus the contralateral side of the brain. Thus, stealth liposomes show potential to enhance drug delivery to the site of brain injury with a wide range of encapsulated therapeutic candidates.

Retracted: Ultrasound‐triggered breast tumor sonodynamic therapy through hematoporphyrin monomethyl ether‐loaded liposome

“…Liposomes are multilamellar or unilamellar phospholipidic submicroscopic vesicles allowing incorporation of hydrophilic and lipophilic drug due to their special properties (Rengan et al, 2015;Zhang et al, 2018). Biocompatible liposome can accumulate in tumor tissue via the enhanced permeability and retention (EPR) effect (Boyd, Galle, Daglas, Rosenfeld, & Medcalf, 2015;Kinoshita et al, 2015;Theek et al, 2016). However, liposomes are unstable under over oxidized environment because the phospholipid is easy to be oxidized.…”

Theranostic Oxygen Reactive Polymers for Treatment of Traumatic Brain Injury

“…For example, delivery of catalase and superoxide dismutase, hydrogen peroxide degrading enzymes, using nanoparticles has been shown to protect neurons from oxidative stress and significantly reduce neuronal damage, further solidifying ROS as a therapeutic target. An enhanced permeability and retention (EPR) effect likely occurs in the anticipated region of treatment due to trauma‐induced breakdown of the BBB . Our use of multifunctional, nanoscaled polymers allows for simultaneous treatment and imaging/diagnosis (theranosis) .…”

Evaluation of host–guest system to enhance the tamoxifen efficiency

“…Because of TMX dose-dependent side effects, use of biocompatible targeted NCs for efficient delivery of TMX can provide maximal pharmacological effects with minimal inadvertent side effects (Yu and Bender 2002). On the other hand, TMX does not has sufficient water solubility to be readily delivered to the tumor cells (Boyd et al 2015). Therefore, with the unique properties of CD we were able to enhance the sustained release of TMX for 120 h. Although, the circulation time is better to be evaluated by the in vivo tests, but long release time of Fe 3 O 4 -DPA-PEG-CD-TMX versus free TMX could confirm the superiority of this system in raising the blood circulation time.…”