Nanoparticles accumulate in ischemic core and penumbra region even when cerebral perfusion is reduced

Ishii, Takayuki; Fukuta, Tatsuya; Agato, Yurika; Oyama, Dai; Yasuda, Nodoka; Shimizu, Kosuke; Kawaguchi, Akira T.; Asai, Tomohiro; Oku, Naoto

doi:10.1016/j.bbrc.2012.12.080

Cited by 31 publications

(18 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, when liposomes were associated with contrast agents, researchers observed that they quickly accumulated in the ischemic zone. 134,143,148,152,190 Some formulations have demonstrated their ability to improve in vivo activity of drugs, such as chrysophanol, 133 dexamethasone phosphate, 154 nerve growth factor, 170 Xe, 150,158 FK506, 149 isopropylidene-shikimic acid, 151 asialo-erythropoietin, 153 antisense oligonucleotides, 165 plasmids, 174 quercetin, 166,168 fasudil, 176 nitric oxide, 146 N-acetylleucyl-leucyl-norleucine amide, 178 and a combination of synergistic drugs. 156,175 Very recently, a promising uncoupling new drug -ZL006 (5-(3, 5-dichloro-2-hydroxybenzylamino)-2-hydroxybenzoic acid) -was developed for stroke treatment.…”

Section: Stroke or Cerebral Ischemiamentioning

confidence: 99%

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Vieira

Gamarra

2016

IJN

346

238

View full text Add to dashboard Cite

This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood–brain barrier. Due to their unique physicochemical characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurological diseases, such as Alzheimer’s, Parkinson’s, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain. Covalent ligation of such macromolecules as peptides, antibodies, and RNA aptamers is an effective method for receptor-targeting liposomes, which allows their blood–brain barrier penetration and/or the delivery of their therapeutic molecule specifically to the disease site. Additionally, methods have been employed for the development of liposomes that can respond to external stimuli. It can be concluded that the development of liposomes for brain delivery is still in its infancy, although these systems have the potential to revolutionize the ways in which medicine is administered.

show abstract

Section: Stroke or Cerebral Ischemiamentioning

confidence: 99%

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Vieira

Gamarra

2016

IJN

346

238

View full text Add to dashboard Cite

show abstract

“…12 Liposomes show several advantages, such as biocompatibility or nontoxicity, ability to protect their cargo from degradation by plasma enzymes, and the capacity to transport their load across biological membranes. 23 To date, liposomes have been used clinically as delivery systems for therapeutic chemotherapeutic agents, antibiotics, and antifungals showing an increase in the safety and efficacy of some drugs.…”

Section: Discussionmentioning

confidence: 99%

“…11 Furthermore, it has been reported that BBB disruption occurs at an early stage after cerebral occlusion, allowing macromolecules to pass through the spaces between capillary endothelial cells. 12 Accordingly, nanoparticles might also be able to leak into brain parenchyma during the acute phase of cerebral ischemia. Interestingly, Sahagun et al 13 suggested that both size and charge of drug carriers are important in determining net brain permeation.…”

Section: Introductionmentioning

confidence: 99%

Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats

Campos-Martorell¹,

Cano‐Sarabia²,

Simats³

et al. 2016

IJN

View full text Add to dashboard Cite

Background and aims Although the beneficial effects of statins on stroke have been widely demonstrated both in experimental studies and in clinical trials, the aim of this study is to prepare and characterize a new liposomal delivery system that encapsulates simvastatin to improve its delivery into the brain. Materials and methods In order to select the optimal liposome lipid composition with the highest capacity to reach the brain, male Wistar rats were submitted to sham or transitory middle cerebral arterial occlusion (MCAOt) surgery and treated (intravenous [IV]) with fluorescent-labeled liposomes with different net surface charges. Ninety minutes after the administration of liposomes, the brain, blood, liver, lungs, spleen, and kidneys were evaluated ex vivo using the Xenogen IVIS ® Spectrum imaging system to detect the load of fluorescent liposomes. In a second substudy, simvastatin was assessed upon reaching the brain, comparing free and encapsulated simvastatin (IV) administration. For this purpose, simvastatin levels in brain homogenates from sham or MCAOt rats at 2 hours or 4 hours after receiving the treatment were detected through ultra-high-protein liquid chromatography. Results Whereas positively charged liposomes were not detected in brain or plasma 90 minutes after their administration, neutral and negatively charged liposomes were able to reach the brain and accumulate specifically in the infarcted area. Moreover, neutral liposomes exhibited higher bioavailability in plasma 4 hours after being administered. The detection of simvastatin by ultra-high-protein liquid chromatography confirmed its ability to cross the blood–brain barrier, when administered either as a free drug or encapsulated into liposomes. Conclusion This study confirms that liposome charge is critical to promote its accumulation in the brain infarct after MCAOt. Furthermore, simvastatin can be delivered after being encapsulated. Thus, simvastatin encapsulation might be a promising strategy to ensure that the drug reaches the brain, while increasing its bioavailability and reducing possible side effects.

show abstract

“…In fact, the liposomes actually accumulated in the brain parenchyma during occlusion, indicating that water flow in a blood vessel is not completely stopped by an occlusion. 90) For evaluation of the liposomal trafficking in the ischemic brain, liposomes were labeled with 1-[…”

Section: Treatment For Ischemic Stroke With Liposomal Neuroprotenctantsmentioning

confidence: 99%

Innovations in Liposomal DDS Technology and Its Application for the Treatment of Various Diseases

Oku

2017

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

Liposomes have been widely used as drug carriers in the field of drug delivery systems (DDS), and they are thought to be ideal nano-capsules for targeting DDS after being injected into the bloodstream. In general, DDS drugs meet the needs of aged and super-aged societies, since the administration route of drugs can be changed, the medication frequency reduced, the adverse effects of drugs suppressed, and so on. In fact, a number of liposomal drugs have been launched and used worldwide including liposomal anticancer drugs, and these drugs have appeared on the market owing to various innovations in liposomal DDS technologies. The accumulation of long-circulating liposomes in cancer tissue is driven by the enhanced permeability and retention (EPR) effect. In this review, liposome-based targeting DDS for cancer therapy is briefly discussed. Since cancer angiogenic vessels are the ideal target of drug carriers after their injection and are critical for cancer growth, damaging of these neovessels has been an approach for eradicating cancer cells. Also, the usage of liposomal DDS for the treatment of ischemic stroke is possible, since we observed that PEGylated liposomes accumulate in the site of cerebral ischemia in transient middle cerebral artery occlusion (t-MCAO) model rats. Interestingly, liposomes carrying neuroprotectants partly suppress ischemia/reperfusion injury of these model rats, suggesting that the EPR effect also works in ischemic diseases by causing an increase in the permeability of the blood vessel endothelium. The potential of liposomal DDS against life-threatening diseases might thus be attractive for supporting long-lived societies.

show abstract

Nanoparticles accumulate in ischemic core and penumbra region even when cerebral perfusion is reduced

Cited by 31 publications

References 26 publications

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats

Innovations in Liposomal DDS Technology and Its Application for the Treatment of Various Diseases

Contact Info

Product

Resources

About

Nanoparticles accumulate in ischemic core and penumbra region even when cerebral perfusion is reduced

Cited by 31 publications

References 26 publications

Getting into the brain: liposome-based strategies for effective drug delivery across the blood&ndash;brain barrier

Getting into the brain: liposome-based strategies for effective drug delivery across the blood&ndash;brain barrier

Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats

Innovations in Liposomal DDS Technology and Its Application for the Treatment of Various Diseases

Contact Info

Product

Resources

About

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier