Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles)

Kreuter, Jörg; Alyautdin, R. N.; Kharkevich, D. A.; Иванов, А. А.

doi:10.1016/0006-8993(95)00023-j

Cited by 502 publications

(283 citation statements)

References 7 publications

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“…[21][22][23] Only pegylated polyalkylcyanoacrylate nanoparticles have lower MPS uptake and prolonged blood circulation in vivo. 24 Brain delivery with PBCA nanoparticles Adsorbed onto polysorbate 80-coated PBCA nanoparticles administered intravenously compounds with poor brain diffusion as diverse as doxorubicin, 25,26 loperamide, 27 tubocurarine, 28 the hexapeptide dalargin 6,7 were successfully delivered to the brain, where they induced a pharmacological effect (for review, see Kreuter 29 ). The chemical nature of the overcoating surfactant is of importance, because only polysorbates, not poloxamers (184, 188, 388, or 407), poloxamine 908, Cremophors (EZ or RH40) or polyoxyethylene(23)-laurylether, led to a CNS pharmacological effect of dalargin.…”

Section: General Considerationsmentioning

confidence: 99%

“…1) have been intensely investigated since the first papers in 1995 showing that when coated with the nonionic surfactant polysorbate 80 they permitted to deliver drugs to the brain. 6,7 Despite interesting results, PBCA nanoparticles have limitations, discussed in this review, that may preclude, or at least limit, their potential clinical applications. Nanoparticles made of polylactide homopolymers (PLA) or poly(lac-tide-co-glycolide) heteropolymers (PLGA) may be a promising alternative.…”

Section: Introductionmentioning

confidence: 99%

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Drug transport to brain with targeted nanoparticles

2005

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Summary: Nanoparticle drug carriers consist of solid biodegradable particles in size ranging from 10 to 1000 nm (50 -300 nm generally). They cannot freely diffuse through the bloodbrain barrier (BBB) and require receptor-mediated transport through brain capillary endothelium to deliver their content into the brain parenchyma. Polysorbate 80-coated polybutylcyanoacrylate nanoparticles can deliver drugs to the brain by a still debated mechanism. Despite interesting results these nanoparticles have limitations, discussed in this review, that may preclude, or at least limit, their potential clinical applications. Long-circulating nanoparticles made of methoxypoly(ethylene glycol)-polylactide or poly(lactide-co-glycolide) (mPEG-PLA/ PLGA) have a good safety profiles and provide drug-sustained release. The availability of functionalized PEG-PLA permits to prepare target-specific nanoparticles by conjugation of cell surface ligand. Using peptidomimetic antibodies to BBB transcytosis receptor, brain-targeted pegylated immunonanoparticles can now be synthesized that should make possible the delivery of entrapped actives into the brain parenchyma without inducing BBB permeability alteration. This review presents their general properties (structure, loading capacity, pharmacokinetics) and currently available methods for immunonanoparticle preparation.

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Section: General Considerationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Drug transport to brain with targeted nanoparticles

2005

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“…We have recently demonstrated that polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles (NPs) enabled an improved distribution of doxorubicin 21 as well as of loperamide, 22 tubocurarine, 23 the hexapeptide dalargin 24 and the NMDA receptor antagonist MRZ 2/576 25 into the brain after i.v. administration.…”

mentioning

confidence: 99%

Chemotherapy of glioblastoma in rats using doxorubicin‐loaded nanoparticles

Steiniger

Kreuter

Khalansky

et al. 2004

Intl Journal of Cancer

400

214

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Glioblastomas belong to the most aggressive human cancers with short survival times. Due to the blood-brain barrier, they are mostly inaccessible to traditional chemotherapy. We have recently shown that doxorubicin bound to polysorbate-coated nanoparticles crossed the intact blood-brain barrier, thus reaching therapeutic concentrations in the brain. Here, we investigated the therapeutic potential of this formulation of doxorubicin in vivo using an animal model created by implantation of 101/8 glioblastoma tumor in rat brains. Groups of 5-8 glioblastoma-bearing rats (total n ‫؍‬ 151) were subjected to 3 cycles of 1.5-2.5 mg/kg body weight of doxorubicin in different formulations, including doxorubicin bound to polysorbate-coated nanoparticles. The animals were analyzed for survival (% median increase of survival time, Kaplan-Meier). Preliminary histology including immunocytochemistry (glial fibrillary acidic protein, ezrin, proliferation and apoptosis) was also performed. Rats treated with doxorubicin bound to polysorbate-coated nanoparticles had significantly higher survival times compared with all other groups. Over 20% of the animals in this group showed a long-term remission. Preliminary histology confirmed lower tumor sizes and lower values for proliferation and apoptosis in this group. All groups of animals treated with polysorbatecontaining formulations also had a slight inflammatory reaction to the tumor. There was no indication of neurotoxicity. Additionally, binding to nanoparticles may reduce the systemic toxicity of doxorubicin. This study showed that therapy with doxorubicin bound to nanoparticles offers a therapeutic potential for the treatment of human glioblastoma.

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“…A range of other transporters, for example the glucose carrier GLUT-1 and the system-L transporter of neutral amino acids could also be exploited for drug design and delivery across the BBB (see Begley 1996). Most remarkable are the observations that poly(butyl)cyanoacrylate nanoparticles (230 nm diameter) coated with the detergent polysorbate-80 appear to penetrate the BBB and release quantities of drug within the brain (Kreuter et al 1995, Schroder & Sabel 1996. A re-examination of the nanoparticle delivery approach for experimental CNS trypanosomiasis should be made.…”

Section: Human African Trypanosomiasismentioning

confidence: 99%

Pharmacological Approaches to Antitrypanosomal Chemotherapy

Croft

1999

Mem. Inst. Oswaldo Cruz

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Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles)

Cited by 502 publications

References 7 publications

Drug transport to brain with targeted nanoparticles

Drug transport to brain with targeted nanoparticles

Chemotherapy of glioblastoma in rats using doxorubicin‐loaded nanoparticles

Pharmacological Approaches to Antitrypanosomal Chemotherapy

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