Polymer Micelles as Drug Carriers

Batrakova, Elena V.; Bronich, Tatiana K.; Vetro, Joseph A.; Kabanov, Alexander V.

doi:10.1142/9781860949074_0005

Cited by 64 publications

(56 citation statements)

References 190 publications

(263 reference statements)

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“…Some studies focusing on the preparations and applications of prodrugs containing DOX have been reported (Liu et al, 2013;Calderón et al, 2009;Ma et al, 2012). The drug delivery system based on block copolymers containing ionic and non-ionic water-soluble segments (''block ionomers'') was proposed in the last decade (Batrakova et al, 2006;Kataoka et al, 2001;Lavasanifar et al, 2002;Riess, 2003). The block ionomers can form nanoparticles in case they react with oppositely charged molecules in aqueous solutions, resulting in polyion complex (PIC), and nanoparticles with agglomerated hydrophobic segments as the core and non-ionic water-soluble segments as the shell (Kabanov et al, 1995;Harada and Kataoka, 1995).…”

Section: Introductionmentioning

confidence: 99%

The polyion complex nano-prodrug of doxorubicin (DOX) with poly(lactic acid-co-malic acid)-block-polyethylene glycol: preparation and drug controlled release

Zhang

Shi

et al. 2014

Med Chem Res

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A polyion complex nano-prodrug based on the complexation of the ionomer of poly(lactic acid-co-malic acid)-block-polyethylene glycol [Poly(LA-co-MA)-b-PEG] with doxorubicin (DOX) was developed. The ionomer was prepared by a direct polycondensation of D,L-lactic acid (LA), L-malic acid (MA), and monomethyl polyethylene glycol (PEG) using stannous chloride (SnCl 2 ) as the catalyst. The nanoparticles were formed through electrostatic interactions between the side carboxyl groups of MA units in the ionomer and amino groups of DOX. The nanoparticle possessed an amphiphilic structure with a hydrophobic core of the complexed DOX and Poly(LA-co-MA) and a hydrophilic shell of PEG. The nanoparticle solution was stable, and the particle sizes were in the range of 110-140 nm. The DOX was loaded as a prodrug with loading rate as high as 18.2 %. The drug release could be controlled, showing responsiveness of acids and ionic strength. The cumulative release was as high as 94 %. The nanoparticles could be potentially used as anti-cancer drug vehicles.

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Section: Introductionmentioning

confidence: 99%

The polyion complex nano-prodrug of doxorubicin (DOX) with poly(lactic acid-co-malic acid)-block-polyethylene glycol: preparation and drug controlled release

Zhang

Shi

et al. 2014

Med Chem Res

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“…Intermolecular interaction between drug and core-forming block drives drug solubilization, and a sense of drug-polymer compatibility may be gained by the calculation of drug and core-forming block solubility parameters (37). Physical and chemical methods for the loading of drugs in polymeric micelles have been described (38). It is noted that many drug candidates have poor aqueous solubility, and for preclinical studies, drug levels >1.0 mg/mL are required for toxicity evaluation in rodents.…”

Section: Polymeric Micelles For Drug Deliverymentioning

confidence: 99%

Polymeric Micelles for Multi-Drug Delivery in Cancer

et al. 2014

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Abstract. Drug combinations are common in cancer treatment and are rapidly evolving, moving beyond chemotherapy combinations to combinations of signal transduction inhibitors. For the delivery of drug combinations, i.e., multi-drug delivery, major considerations are synergy, dose regimen (concurrent versus sequential), pharmacokinetics, toxicity, and safety. In this contribution, we review recent research on polymeric micelles for multi-drug delivery in cancer. In concurrent drug delivery, polymeric micelles deliver multi-poorly water-soluble anticancer agents, satisfying strict requirements in solubility, stability, and safety. In sequential drug delivery, polymeric micelles participate in pretreatment strategies that "prime" solid tumors and enhance the penetration of secondarily administered anticancer agent or nanocarrier. The improved delivery of multiple poorly water-soluble anticancer agents by polymeric micelles via concurrent or sequential regimens offers novel and interesting strategies for drug combinations in cancer treatment.

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“…Core-shell polymer micelles (PM) are being widely developed as an alternative, less toxic approach to improve the IV administration of low MW drugs with poor aqueous solubility (5, 6). The most developed core-shell PM are formed from amphiphilic diblock (hydrophilic-hydrophobic) copolymers or triblock (hydrophilic-hydrophobic-hydrophilic) copolymers (7–9) such as Pluronic F127 (poloxamer 407) (8) that spontaneously self-assemble into spherical, nano-sized micelles when the unimers are directly or indirectly dissolved in aqueous solution above a threshold concentration (critical micelle concentration, CMC) and solution temperature (critical micelle temperature, CMT) (5) (Fig.1A).…”

Section: Introductionmentioning

confidence: 99%

“…The most developed core-shell PM are formed from amphiphilic diblock (hydrophilic-hydrophobic) copolymers or triblock (hydrophilic-hydrophobic-hydrophilic) copolymers (7–9) such as Pluronic F127 (poloxamer 407) (8) that spontaneously self-assemble into spherical, nano-sized micelles when the unimers are directly or indirectly dissolved in aqueous solution above a threshold concentration (critical micelle concentration, CMC) and solution temperature (critical micelle temperature, CMT) (5) (Fig.1A). Core-shell PM then consist of a hydrophobic core for drug loading and a hydrophilic shell to prevent the aggregation of PM before and after IV administration and, ideally, protect loaded drug while localizing to the site of drug action (5). …”

Section: Introductionmentioning

confidence: 99%

“…Hydrophobic, low MW drugs can be loaded into core-shell polymer micelles by chemically conjugating the drug to the hydrophobic block before self-assembly (10–14) or by physically loading the drug into the hydrophobic core during or after self-assembly (5). Physical loading is generally preferred over chemical conjugation, however, because higher levels of drug loading are possible (15) and because many drug molecules must be additionally modified to facilitate chemical conjugation (5), whereas the hydrophobic block can be easily modified to increase physical drug loading without changing the original drug molecule (16–18).…”

Section: Introductionmentioning

confidence: 99%

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Peripherally Cross-Linking the Shell of Core-Shell Polymer Micelles Decreases Premature Release of Physically Loaded Combretastatin A4 in Whole Blood and Increases its Mean Residence Time and Subsequent Potency Against Primary Murine Breast Tumors After IV Administration

Wakaskar¹,

Bathena²,

Tallapaka³

et al. 2014

Pharm Res

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Purpose Determine the feasibility and potential benefit of peripherally cross-linking the shell of core-shell polymer micelles on the premature release of physically loaded hydrophobic drug in whole blood and subsequent potency against solid tumors. Methods Individual Pluronic F127 polymer micelles (F127 PM) peripherally cross-linked with ethylenediamine at 76% of total PEO blocks (X-F127 PM) were physically loaded with combretastatin A4 (CA4) by the solid dispersion method and compared to CA4 physically loaded in uncross-linked F127 PM, CA4 in DMSO in vitro, or water-soluble CA4 phosphate (CA4P) in vivo. Results X-F127 PM had similar CA4 loading and aqueous solubility as F127 PM up to 10 mg CA4 / mL at 22.9 wt% and did not aggregate in PBS or 90% (v/v) human serum at 37°C for at least 24 h. In contrast, X-F127 PM decreased the unbound fraction of CA4 in whole blood (fu) and increased the mean plasma residence time and subsequent potency of CA4 against the vascular function and growth of primary murine 4T1 breast tumors over CA4 in F127 PM and water-soluble CA4P after IV administration. Conclusions Given that decreasing the fu is an indication of decreased drug release, peripherally cross-linking the shell of core-shell polymer micelles may be a simple approach to decrease premature release of physically loaded hydrophobic drug in the blood and increase subsequent potency in solid tumors.

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Polymer Micelles as Drug Carriers

Cited by 64 publications

References 190 publications

The polyion complex nano-prodrug of doxorubicin (DOX) with poly(lactic acid-co-malic acid)-block-polyethylene glycol: preparation and drug controlled release

The polyion complex nano-prodrug of doxorubicin (DOX) with poly(lactic acid-co-malic acid)-block-polyethylene glycol: preparation and drug controlled release

Polymeric Micelles for Multi-Drug Delivery in Cancer

Peripherally Cross-Linking the Shell of Core-Shell Polymer Micelles Decreases Premature Release of Physically Loaded Combretastatin A4 in Whole Blood and Increases its Mean Residence Time and Subsequent Potency Against Primary Murine Breast Tumors After IV Administration

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