A new class of drug carriers: micelles of poly(oxyethylene)-poly(oxypropylene) block copolymers as microcontainers for drug targeting from blood in brain

Kabanov, Alexander V.; Batrakova, Elena V.; Melik‐Nubarov, N. S.; Fedoseev, N. A.; Dorodnich, Tatiyana Yu.; Alakhov, Valery; Чехонин, В. П.; Nazarova, I. R.; Kabanov, V.A.

doi:10.1016/0168-3659(92)90199-2

Cited by 281 publications

(169 citation statements)

References 13 publications

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“…Further, due to charge neutralization these complexes are often unstable in aqueous solutions and precipitate, thereby hindering their application in gene delivery [3 8]. One approach recently advanced for drug delivery of water insoluble compounds involves the use of micelles of Pluronic block copolymers [9,10]. Recent work on these systems suggests that they enhance the transport of charged molecules across cell membranes [11,12].…”

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confidence: 99%

Enhancement of the polycation‐mediated DNA uptake and cell transfection with Pluronic P85 block copolymer

et al. 1996

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Polyelectrolyte complexes formed between DNA and poly(N-ethyl-4-vinylpyridinium) cations were shown to effectively transfect mammalian ceils [7]. This work suggests that the polycation-mediated uptake of the plasmid DNA and cell transfection are significantly enhanced when these complexes are administered simultaneously with a poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) copolymer, Pluronic P85. The uptake studies were performed using radioactively labeled pRSV CAT plasmid on NIH 3T3, MDCK, and Jurkat cell lines. The transfection was investigated by ehloramphenicol acetyltransferase assay using 3T3 cells as a model. The effects reported may be useful for the enhancement of the polycation-mediated cell transfection.cytic compartments in the cytoplasm and nucleus of cells [1 3]. Further, due to charge neutralization these complexes are often unstable in aqueous solutions and precipitate, thereby hindering their application in gene delivery [3 8]. One approach recently advanced for drug delivery of water insoluble compounds involves the use of micelles of Pluronic block copolymers [9,10]. Recent work on these systems suggests that they enhance the transport of charged molecules across cell membranes [11,12]. This paper reports a significant increase in cell uptake and transfection of mammalian cells using a combination of DNA-PEVP complexes and micelles of Pluronic P85 block copolymer.

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confidence: 99%

Enhancement of the polycation‐mediated DNA uptake and cell transfection with Pluronic P85 block copolymer

et al. 1996

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“…These micelles represent self-assembled structures with a core formed by the hydrophobic segments and a corona formed by the hydrophilic segments. A great variety of drugs can be non-covalently incorporated into such micelles by simple mixing with the block copolymer solutions (Kabanov et al, 1992). Drug molecules can also be covalently linked to the repeating units of the copolymer segment (Bader et al, 1984).…”

mentioning

confidence: 99%

Anthracycline antibiotics non-covalently incorporated into the block copolymer micelles: in vivo evaluation of anti-cancer activity

Batrakova

Dorodnych²,

Klinskii³

et al. 1996

Br J Cancer

210

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Summary The chemosensitising effects of poly(ethylene oxide)-poly(propylene oxide)-poly-(ethylene oxide) (PEO-PPO-PEO) block copolymers (Pluronic) in multidrug-resistant cancer cells has been described recently (Alakhov VY, Moskaleva EY, Batrakova EV, Kabanov AV 1996, Biocon. Chem., 7, 209). This paper presents initial studies on in vivo evaluation of Pluronic copolymers in the treatment of cancer. The anti-tumour activity of epirubicin (EPI) and doxorubicin (DOX), solubilised in micelles of Pluronic L61, P85 and F108, was investigated using murine leukaemia P388 and daunorubicin-sensitive Sp2/0 and -resistant Sp2/0DNR myeloma cells grown subcutaneously (s.c.). The study revealed that the lifespan of the animals and inhibition of tumour growth were considerably increased in mice treated with drug/copolymer compositions compared with animals treated with the free drugs. The anti-tumour activity of the drug/copolymer compositions depends on the concentration of the copolymer and its hydrophobicity, as determined by the ratio of the lengths of hydrophilic PEO and hydrophobic PPO segments. The data suggest that higher activity is associated with more hydrophobic copolymers. In particular, a significant increase in lifespan (TIC> 150%) and tumour growth inhibition (>90%) was observed in animals with Sp2/0 tumours with EPI/P85 and DOX/L61 compositions. The effective doses of these compositions caused inhibition of Sp2/0 tumour growth and complete disappearance of tumour in 33-50% of animals. Future studies will focus on the evaluation of the activity of Pluronic-based compositions against human drug-resistant tumours.

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“…One early study used micelles of Pluronic ® block copolymers (PEG-b-PPG-b-PEG) as carriers for CNS drug delivery [123,214]. These micelles were conjugated with either polyclonal antibodies against brain α 2 -glycoprotein or insulin as targeting moieties.…”

Section: Polymeric Micellesmentioning

confidence: 99%

“…These micelles were conjugated with either polyclonal antibodies against brain α 2 -glycoprotein or insulin as targeting moieties. Both antibody-and insulin-vectorized micelles were shown to deliver a drug or a fluorescent probe to brain in vivo [214]. Furthermore, there was a considerable increase in neuroleptic activity of a drug (haloperidol) solubilized in the targeted micelles compared to a free drug.…”

Section: Polymeric Micellesmentioning

confidence: 99%

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

Kabanov

Gendelman

2007

Progress in Polymer Science

242

138

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Neurodegenerative and infectious disorders including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and stroke are rapidly increasing as population's age. Alzheimer's disease alone currently affects 4.5 million Americans, and more than $100 billion is spent per year on medical and institutional care for affected people. Such numbers will double in the ensuing decades. Currently disease diagnosis for all disorders is made, in large measure, on clinical grounds as laboratory and neuroimaging tests confirm what is seen by more routine examination. Achieving early diagnosis would enable improved disease outcomes. Drugs, vaccines or regenerative proteins present "real" possibilities for positively affecting disease outcomes, but are limited in that their entry into the brain is commonly restricted across the blood-brain barrier. This review highlights how these obstacles can be overcome by polymer science and nanotechnology. Such approaches may improve diagnostic and therapeutic outcomes. New developments in polymer science coupled with cell-based delivery strategies support the notion that diseases that now have limited therapeutic options can show improved outcomes by advances in nanomedicine.

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A new class of drug carriers: micelles of poly(oxyethylene)-poly(oxypropylene) block copolymers as microcontainers for drug targeting from blood in brain

Cited by 281 publications

References 13 publications

Enhancement of the polycation‐mediated DNA uptake and cell transfection with Pluronic P85 block copolymer

Enhancement of the polycation‐mediated DNA uptake and cell transfection with Pluronic P85 block copolymer

Anthracycline antibiotics non-covalently incorporated into the block copolymer micelles: in vivo evaluation of anti-cancer activity

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

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