Covalent attachment of apolipoprotein A-I and apolipoprotein B-100 to albumin nanoparticles enables drug transport into the brain

Kreuter, Jörg; Hekmatara, T.; Dreis, Sebastian; Vogel, Thomas; Gelperina, Svetlana; Langer, Klaus

doi:10.1016/j.jconrel.2006.12.012

Cited by 243 publications

(130 citation statements)

References 28 publications

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“…The possibility that lipoproteins cross the BBB has been suggested by the presence of lipoprotein receptors on BBB cells, and by the observation that peptides derived from ApoE and ApoB promote transport of linked proteins across the BBB (Balazs et al, 2004;Kreuter et al, 2007;Spencer and Verma, 2007;Candela et al, 2008;Zensi et al, 2009). Nevertheless, there has been no evidence to show that circulating lipoproteins cross the BBB in vivo, or what their function in the brain might be if they did.…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein Particles Cross the Blood–Brain Barrier inDrosophila

Brankatschk

Eaton

2010

J. Neurosci.

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The blood-brain barrier (BBB) regulates passage of nutrients and signaling molecules from the circulation into the brain. Whether lipoproteins cross the BBB in vivo has been controversial, and no clear requirement for circulating lipoproteins in brain development has been shown. We address these issues in Drosophila, which has an functionally conserved BBB, and lipoproteins that resemble those of vertebrates. We show that the Drosophila lipoprotein lipophorin exists in two isoforms. Both isoforms cross the BBB, but accumulate on distinct subsets of cells within the brain. In addition to acting as a lipid carrier, lipophorin carries both sterol-linked and GPI-linked proteins into the circulation and transports them across the BBB. Finally, lipophorin promotes neuroblast proliferation by a mechanism that does not depend on delivery of dietary lipids. Transport of lipophorin and its cargo across the BBB represents a novel mechanism by which peripherally synthesized proteins might enter the brain and influence its development. Furthermore, lipid-linkage may be an efficient method to transport therapeutic molecules across the BBB.

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Section: Discussionmentioning

confidence: 99%

Lipoprotein Particles Cross the Blood–Brain Barrier inDrosophila

Brankatschk

Eaton

2010

J. Neurosci.

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“…It appears to be achieved by covalent coupling with apolipoprotein E, A-I, or B-100, followed by receptor-mediated endocytosis of the nanoparticles by the brain capillary endothelial cells. 21,22 Temozolomide ( The solubility of TMZ in normal saline is 3.1 mg/mL. 24 It has been shown to be one of the most effective antineoplastic agents for treating high-grade glioma and metastatic melanoma.…”

Section: Introductionmentioning

confidence: 99%

Enhanced brain targeting of temozolomide in polysorbate-80 coated polybutylcyanoacrylate nanoparticles

Tian¹,

Lin²,

Feng³

et al. 2011

IJN

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Natural Science Foundation of Fujian Province of China; Xiamen Science and Technology Bureau of ChinaBackground: Polybutylcyanoacrylate (PBCA) nanoparticles coated with polysorbate-80 have been extensively proposed for delivering drugs into the animal brain and have shown great potential for therapeutic applications. In this study, we made an attempt to deliver the chemotherapeutic drug, temozolomide, into the brain by using PBCA nanoparticles. The physicochemical characteristics, in vitro release, and brain targeting ability of the drug-loaded nanoparticles were investigated. Results: Our results show that a significantly higher concentration of temozolomide in the form of polysorbate-80-coated PBCA nanoparticles was observed in the brain (P < 0.05) in comparison with the free drug. Conclusion: This study indicates that polysorbate-80 coated PBCA nanoparticles could be a feasible carrier for temozolomide delivery to the brain. It is anticipated that the developed formulation may improve on targeted therapy for malignant brain tumors in the future

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“…Therefore, the nanoparticles mimic low-density lipoproteins and interact with the brain capillary endothelial cells, finally transferring the drug into the brain via receptor-mediated endocytosis. A recent study examined the effectiveness of other apolipoproteins, such as ApoE3, B-100, and A-I, in brain targeting, 21 showing the existence of more than one nanoparticle-brain endothelium interaction mechanism. We also hypothesize that, due to the small size of the complex particles, many of them escape uptake by phagocytic cells of the liver, spleen, and reticuloendothelial system and may account for the significantly lower accumulation of AmB found in these tissues compared with noncomplexed AmB (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of intravenous amphotericin B-polybutylcyanoacrylate nanoparticles against cryptococcal meningitis in mice

Xu¹,

Gu²,

Zhu³

et al. 2011

IJN

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Amphotericin B deoxycholate (AmB), a classic antifungal drug, remains the initial treatment of choice for deep fungal infections, but it is not appropriate for treatment of cryptococcal meningitis due to its inability to pass through the blood–brain barrier (BBB). We examined the efficacy of amphotericin B-polybutylcyanoacrylate nanoparticles (AmB-PBCA-NPs) modified with polysorbate 80 that had a mean particle diameter less than 100 nanometers (69.0 ± 28.6 nm). AmB-PBCA-NPs were detected in the brain 30 minutes after systemic administration into BALB/c mice and had a higher concentration than systemically administered AmB liposome (AmB-L, P < 0.05); AmB was not detected in the brain. Following infection for 24 hours and then 7 days of treatment, the survival rate of mice in the AmB-PBCA-NP group (80%) was significantly higher than that of the AmB (0%) or AmB-L (60%) treatment groups. Fungal load was also lower when assessed by colony-forming unit counts obtained after plating infected brain tissue ( P < 0.05). Our study indicates that AmB-PBCA-NPs with polysorbate 80 coating have the capacity to transport AmB across the BBB and is an efficient treatment against cryptococcal meningitis in a mouse model.

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Covalent attachment of apolipoprotein A-I and apolipoprotein B-100 to albumin nanoparticles enables drug transport into the brain

Cited by 243 publications

References 28 publications

Lipoprotein Particles Cross the Blood–Brain Barrier inDrosophila

Lipoprotein Particles Cross the Blood–Brain Barrier inDrosophila

Enhanced brain targeting of temozolomide in polysorbate-80 coated polybutylcyanoacrylate nanoparticles

Efficacy of intravenous amphotericin B-polybutylcyanoacrylate nanoparticles against cryptococcal meningitis in mice

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