Block copolymer micelles as long-circulating drug vehicles

Kwon, Glen S.; Kataoka, Kazunori

doi:10.1016/0169-409x(95)00031-2

Cited by 779 publications

(579 citation statements)

References 37 publications

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“…Generally high entrapment efficiencies could only be achieved when complex methods were used to prepare the drug loaded micelles or nanoparticles. Often the use of organic solvents and/or heat were necessary (2,3,10,(28)(29)(30)(31)(32)(33). In contrast, the mmePEG750-initiated CAP/TMC copolymers described in this paper form spontaneously a clear solution upon dispersion in water and solubilize in an easy way poorly water-soluble drugs.…”

Section: Discussionmentioning

confidence: 99%

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Biodegradable Self-Assembling PEG-Copolymer as Vehicle for Poorly Water-Soluble Drugs

Ould-Ouali

Ariën²,

Rosenblatt

et al. 2004

Pharm Res

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Purpose. To develop self-assembling systems increasing the solubility of poorly water-soluble drugs. Methods. Low molecular weight liquid biodegradable copolymers were synthesized by ring-opening polymerization using caprolactone (CAP) and trimethylenecarbonate (TMC) as monomers. Various initiators were evaluated. The emulsifying and self-assembling properties were investigated by a water titration method. The selfassembling systems were characterized for size, shape, isotropic behavior, cloud point, surface charge, and critical micellar concentration in order to optimize the polymer synthesis. Finally, the improvement of solubility of model drugs was assessed. Results. Only diblock monomethyl ether PEG-CAP/TMC copolymers synthesized with monomethyl ether polyethyleneglycol 550 to 2000 as initiator have shown self-assembling properties: upon dilution, these copolymers formed an isotropically clear solution with droplet sizes in the range of 20 to 100 nm. The hypothesis that these diblock polymers form micelles was confirmed by their low critical micellar concentration (10 −5 g/ml). The copolymers initated with mmePEG750 had a higher cloud point and better colloidal stability than those initiated with mmePEG 550. The solubility of the poorly water-soluble drugs was increased by 1 to 2 orders of magnitude. Good reproducibility was observed from batch to batch. Conclusions. The polyester diblock copolymer mmePEG750-CAP/ TMC forms spontaneously stable micelles in aqueous medium and increases the solubility of lipophilic drugs. They are very promising vehicles for the oral delivery of poorly water-soluble drugs.

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Section: Discussionmentioning

confidence: 99%

“…However, the incorporation of drugs into diblock polymeric micelles is usually a long and multi-step procedure, which often requires the use of organic solvents (for reviews, see Refs. 2,3,[10][11][12][13][14]. There are various methods for the incorporation of drugs in the blockcopolymer micelles.…”

Section: Introductionmentioning

confidence: 99%

Biodegradable Self-Assembling PEG-Copolymer as Vehicle for Poorly Water-Soluble Drugs

Ould-Ouali

Ariën²,

Rosenblatt

et al. 2004

Pharm Res

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“…To improve therapeutic efficacy while minimizing side effects, various drug delivery and targeting systems have been investigated such as synthetic polymer-drug conjugates (3), liposomes (4), micelles (5,6), nanogels (7), and micro-or nanosphere (8,9). Nano-sized delivery systems are able to passively accumulate drugs in solid tumors by an enhanced permeation and retention (EPR) effect (10).…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin Loaded pH-sensitive Micelle: Antitumoral Efficacy against Ovarian A2780/DOXR Tumor

Kim¹,

Lee²,

Park³

et al. 2008

Pharm Res

107

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Purpose-To evaluate pH-sensitive mixed micelles for multidrug resistant (MDR) ovarian tumor targeting and optical imaging of solid tumors.Method-Doxorubicin (DOX) encapsulated pH-sensitive mixed micelles composed of poly(Lhistidine) (MW 5K)-b-PEG(MW 2K) and poly(L-lactic acid)(3K)-b-PEG (2K)-folate (PHSM-f) were prepared. Folate receptor-mediated endocytosis, drug uptake, endosomal disruption and cell viability were investigated at the cellular level. For in vivo tumor growth inhibition tests, multidrug resistant ovarian A2780/DOX R xenografted nude mice were used. Optical imaging was performed by using a Cy5.5 fluorescence dye-labeled mixed micelle system. Cy5.5 fluorescence intensity at the tumor site was measured in KB epidermoid xenografted nude mice.Results-In vitro cell viability and drug distribution in the cytoplasm demonstrated the significantly superior efficacy of PHSM-f to free DOX and a control sample of DOX loaded pH-insensitive micelle composed of poly(L-lactic acid)(3K)-b-PEG(2K)/poly(L-lactic acid)(3K)-b-PEG(2K)-folate (80/20 wt/wt%) (PHIM-f). The mechanisms of these results were proved by folate receptor mediated endocytosis of micelle and endosomal disruption function by it. In addition, the optical imaging demonstrated the future application of the diagnositic area. PHSM-f inhibited the growth of multidrug resistant ovarian tumors efficiently in mice, with minimum weight loss.Conclusions-The pH-sensitive mixed micelle system demonstrates effective antitumor efficacy against the multidrug resistant ovarian tumor A2780/DOX R .

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“…As far as we know, there is no record that links the arrangement of the polymer section to the antifungal activity of the component. Most related literature deals with the design and synthesis of (block co) polymers with as its aim the solubilisation of a membrane active molecule, such as amphtericin B (Kwon and Kataoka, 1995;Yu et al, 1998).…”

Section: Article In Pressmentioning

confidence: 99%

Efficacy of alcohol alkoxylate surfactants differing in the molecular structure of the hydrophilic portion to control Phytophthora nicotianae in tomato substrate culture

2007

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Phytophthora nicotianae is a common and destructive pathogen of numerous ornamental, agronomic and horticultural crops such as tomato, tobacco and citrus. Three monobranched C 13 alcohol alkoxylate non-ionic surfactants were evaluated for in vitro inhibitory activity against the different asexual structures of P. nicotianae. The same surfactants, labelled MBA1301, MBA1303 and MBA1306, were tested for their in vivo control capacity against P. nicotianae root rot of tomato (Lycopersicon esculentum) under glasshouse conditions. MBA1301, MBA1303 and MBA1306 differ in the molecular structure of the hydrophilic portion. The molecular weight of MBA1301 is comparable to that of MBA1303 and is eight times lower than that of MBA1306. The main in vitro activity for MBA1301 and MBA1303 was a direct lytic effect on the zoospores. Zoospore lysis was already observed in the presence of 1 mg ml À1 of these two surfactants and almost no zoospores survived an addition of 5 mg ml À1 surfactant. In addition, MBA1301 and MBA1303 reduced sporangia formation at a concentration of 5 mg ml À1 . Both surfactants only affect mycelium growth at concentrations as high as 100 mg ml À1 . MBA1306 did not show any effect on sporangia formation, zoospore release and mycelium growth of P. nicotianae at a concentration 10 times that of the other two surfactants. A good in vivo control of P. nicotianae on tomato in substrate culture was obtained for MBA1301 and MBA1303 whereas the control capacity of MBA1306 was significantly lower. The results of this research indicate that non-ionic alcohol alkoxylate surfactants can be used to control tomato root rot caused by P. nicotianae in substrate culture. In addition, the size rather than the arrangement of the polymers in the hydrophilic portion of the surfactant molecule determines the efficacy to control tomato root rot caused by P. nicotianae in substrate culture. r

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Block copolymer micelles as long-circulating drug vehicles

Cited by 779 publications

References 37 publications

Biodegradable Self-Assembling PEG-Copolymer as Vehicle for Poorly Water-Soluble Drugs

Biodegradable Self-Assembling PEG-Copolymer as Vehicle for Poorly Water-Soluble Drugs

Doxorubicin Loaded pH-sensitive Micelle: Antitumoral Efficacy against Ovarian A2780/DOXR Tumor

Efficacy of alcohol alkoxylate surfactants differing in the molecular structure of the hydrophilic portion to control Phytophthora nicotianae in tomato substrate culture

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