Applications of Liposomal Drug Delivery Systems to Develop Neuroprotective Agents for the Treatment of Ischemic Stroke

Ischemic stroke is one of the leading causes of severe disability and death. In clinical settings, tissue plasminogen activator (t-PA) for thrombolytic therapy is the only globally approved drug for the treatment of ischemic stroke. However, the proportion of patients who receive t-PA therapy is ext...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2019/03/01, Vol.42(3), pp.319-326
Main Authors: Fukuta, Tatsuya, Ishii, Takayuki, Asai, Tomohiro, Oku, Naoto
Format: Article
Language:English
Subjects:
Blood-brain barrier
Brain
cerebral ischemia–reperfusion injury
Diuretics
Drug delivery
drug delivery system
Drug delivery systems
Drug development
Hemorrhage
Ischemia
ischemic stroke
liposome
Liposomes
Membrane permeability
nanoparticle
Nanoparticles
Neuroprotection
Neuroprotective agents
Patients
Permeability
Reperfusion
Stroke
t-Plasminogen activator
Thrombolysis
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Summary:Ischemic stroke is one of the leading causes of severe disability and death. In clinical settings, tissue plasminogen activator (t-PA) for thrombolytic therapy is the only globally approved drug for the treatment of ischemic stroke. However, the proportion of patients who receive t-PA therapy is extremely limited due to its narrow therapeutic time window (TTW) and the risk of cerebral hemorrhage. Cerebral ischemia–reperfusion (I/R) injury is also a serious problem for patients’ outcomes. Hence, the development of more effective therapies has been desired to prolong the TTW of t-PA and prevent cerebral I/R injury. For delivering drugs into the brain, the blood–brain barrier (BBB) must be overcome since it limits drug penetration into the brain, leading to insufficient therapeutic efficacy. As a distinctive pathology after an ischemic stroke, it was reported that the vascular permeability of the BBB is increased around the ischemic region. We found that nano-sized liposomes can pass through the disrupted BBB and accumulate in the I/R region, and that delivery of neuroprotective agents using a liposomal drug delivery system (DDS) is effective for the treatment of cerebral I/R injury. Moreover, we have recently demonstrated that combination therapy with liposomal drugs and t-PA can suppress the deleterious effects of t-PA and extend its TTW in a rat ischemic stroke model. These findings indicate that applications of nanoparticle DDS technology could be a hopeful approach to drug development for ischemic stroke therapy. In this review, we introduce our findings on ischemic stroke treatment using liposomal DDS and recent advances from other research groups.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b18-00683