Targeting ischemic penumbra Part II: selective drug delivery using liposome technologies

Abstract

In the present review (part II), we discuss the challenges and promises of selective drug delivery to ischemic brain tissue by liposome technologies. In part I of this serial review, we proposed “selective drug delivery to ischemic brain tissue” as a technique for neuroprotective treatment of acute ischemic stroke. To be effective, drugs must pass a series of barriers to arrive at ischemic brain. Brain ischemia results in metabolic and structural changes in the ischemic region, which cause additional obstacles for drug delivery. Liposome drug delivery system can pass these barriers and selectively target ischemic tissue by utilizing ischemia-induced changes in metabolism and molecular structure.

Improving Cerebral Blood Flow Through Liposomal Delivery of Angiogenic Peptides: Potential of 18F-FDG PET Imaging in Ischemic Stroke Treatment

“…Cerebral ischemia causes a broad spectrum of pathophysiologic changes, including blood-brain barrier disruptions and increased vascular permeability: the enhanced permeability and retention effect. Previous studies have shown that an increase in vascular permeability by ischemia may enable selective targeting of drugs at the critical site of action, allowing effective drug delivery to the ischemic hemisphere of the brain (14,15). Our results of g imaging by 99m Tc-HMPAO (supplemental materials) clearly demonstrated liposomal accumulation in the ischemic hemisphere of the brain.…”

Nanoliposome containing cyclosporine A reduced neuroinflammation responses and improved neurological activities in cerebral ischemia/reperfusion in rat

“…It has been confirmed that during ischemia reperfusion, the secondary cerebral damages due to BBB disruption and permeabilization of the vascular endothelial cells permit penetration of nanoliposomes into the ischemic brain . In this experiment, we applied extrusion method to make monodisperse nanoliposomes to enhance penetration of carrier into the brain after I/R induction . We also used DOPE phospholipid in liposome bilayer to involve endosomal escape after the endocytosis where efficient intracellular delivery of CsA is necessary as a peptide .…”

“…Among the novel drug delivery systems, nanoliposomes are well known as safe and designable carrier that can be made for efficient delivery of drugs into the brain tissue after ischemia reperfusion [10][11][12]. It has been confirmed that during ischemia reperfusion, the secondary cerebral damages due to BBB disruption and permeabilization of the vascular endothelial cells permit penetration of nanoliposomes into the ischemic brain [10,12]. In this experiment, we applied extrusion method to make monodisperse nanoliposomes to enhance penetration of carrier into the brain after I/R induction [12].…”

“…Liposomes with unique properties in delivery of protein and peptides can improve deficits in brain targeting [11]. It is evidenced that nanosized liposomes are nontoxic and successful in accumulation of their cargo in brain tissue and reduced effective dose of drug in amelioration of brain injury models [12,13]. Furthermore, in-vitro and in-vivo reports showed that liposomal CsA containing phosphatidylserine (PS) and phosphatidylethanolamine (DOPE) phospholipids dramatically enhanced pharmacologic effects of CsA in experimental models [14,15].…”

Biomechanical and biochemical compatibility in innovative biomaterials

“…A targeted drug delivery is the key to achieve a satisfactory therapeutic outcome, otherwise the drug may end up in a different part of the © Woodhead Publishing Limited, 2012 body, and toxic to healthy tissues. 'Smart' pH-sensitive nanoliposomes are being developed that are stable at physiological pH but in the acidic environment they undergo degradation and release the active substance (Liu et al ., 2011).…”