Nano-engineering block copolymer aggregates for drug delivery

Allen, Christine; Maysinger, Dušica; Eisenberg, Adi

doi:10.1016/s0927-7765(99)00058-2

Cited by 1,321 publications

(1,202 citation statements)

References 93 publications

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“…Therefore, we used PEG-b-PBC to load rapamycin because the presence of aromatic moieties in the hydrophobic block will help to increase the compatibility of polymer and drug with hydrophobic ring structures. 23,24 In our previous studies, it was found that the solubility of bicalutamide in micelles was significantly increased by adding the polycarbonate moieties into PEG-b-P(CB-co-LA). 16 Similar to our previous study, we also found that the drug loading increased with increasing hydrophobic block length ( Table 2).…”

Section: Discussionmentioning

confidence: 99%

“…19 The release of drug from polymeric micelles is influenced by several factors including polymer hydrophobic core length and structure, physical state of the core, amount and properties of incorporated drugs, strength of the interaction between drug and hydrophobic core, and location of the drug loading. 27 The drug loaded close to the interface of hydrophobic core and hydrophilic block diffuses faster than drugs loaded deep in the hydrophobic core. As we observed in Figure 5, PEG 114 -b-PBC 17 and PEG 114 -b-PBC 30 demonstrated a similar release profile at the first 8 h, this is probably due to the fast diffusion of drugs loaded close to the interface.…”

Section: Discussionmentioning

confidence: 99%

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Poly(ethylene glycol)-Block-Poly(2-methyl-2-benzoxycarbonyl-propylene Carbonate) Micelles for Rapamycin Delivery: In Vitro Characterization and Biodistribution

Mahato

2011

Journal of Pharmaceutical Sciences

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Our objective was to synthesize an amphiphilic diblock copolymer for micellar delivery of rapamycin. Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate) (PEG-b-PBC) with different hydrophobic core lengths were synthesized from methoxy poly(ethylene glycol) and 2-methyl-2-benzoxycarbonyl-propylene carbonate through ring-opening polymerization using 1,8-diazabicycloundec-7-ene as a catalyst. The critical micelle concentration of PEG-b-PBC was around 10 −8 M and depends on the hydrophobic core length. Rapamycin was effectively incorporated into micelles and drug loading increased with increasing hydrophobic core length, with maximal drug loading of 10% (w/w, drug/polymer), drug loading efficiency of about 85%, and mean particle size of around 70 nm. The drug release profile was also dependent on the hydrophobic core length and the drug release from PEG 114 -b-PBC 30 micelles was the slowest. We also determined the toxicity of rapamycin micelles on insulinoma (INS-1E) $-cells and human islets. Encapsulation of rapamycin into PEG-b-PBC micelles reduced its toxicity. Biodistribution of rapamycin-loaded PEG-b-PBC micelles was determined after systemic administration into mice. Rapamycin-loaded PEG-b-PBC micelles showed little difference in pharmacokinetics and biodistribution characteristics in mice compared with rapamycin carrying nanosuspension. In conclusion, rapamycin formulated with PEG-b-PBC micelles showed significantly reduced toxicity on INS-1E $-cells and human islets, but had similar biodistribution profiles as those of nanosuspensions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Poly(ethylene glycol)-Block-Poly(2-methyl-2-benzoxycarbonyl-propylene Carbonate) Micelles for Rapamycin Delivery: In Vitro Characterization and Biodistribution

Mahato

2011

Journal of Pharmaceutical Sciences

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“…Also, an increase in the length of the hydrophilic block resulted in a decrease in the cmc when the length of the hydrophobic block was held constant for diblock copolymers, PEG-b-PCL. 52 It is not only the hydrophilic-lipophilic balance the factor that governs the association of these copolymers into diverse nanostructured particles; rather, it is also that the specific topology of the different blocks significantly influences the micellar morphology. The self assembly behavior of these rod-coil copolymers was governed by the effect of chain topology on conformational entropy, which restricted their ability to stretch, to accommodate packing within selfassembled structures and their ability to gain conformational entropy when dissolved in solution.…”

Section: Discussionmentioning

confidence: 99%

Hierarchically organized micellization of thermoresponsive rod‐coil copolymers based on poly[oligo(ethylene glycol) methacrylate] and poly(ε‐caprolactone)

Luzon

Corrales

Catalina

et al. 2010

J. Polym. Sci. A Polym. Chem.

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A series of amphiphilic triblock copolymers, poly [oligo(ethylene glycol) methacrylate] x -block-poly(e-caprolactone)-block-poly[oligo(ethylene glycol) methacrylate] x , POEGMA Co (x), were synthesized. Formation of hydrophobic domains as cores of the micelles was studied by fluorescence spectroscopy. The critical micelle concentrations in aqueous solution were found to be in the range of circa 10 À6 M. A novel methodology by modulated temperature differential scanning calorimetry was developed to determine critical micelle temperature. A significant concentration dependence of cmt was found. Dynamic light scattering measurements showed a bidispersed size distribution.The micelles showed reversible dispersion/aggregation in response to temperature cycles with lower critical solution temperature between 75 and 85 C. The interplay of the two hydrophobic and one thermoresponsive macromolecular chains offers the chance to more complex morphologies. V C 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: [4909][4910][4911][4912][4913][4914][4915][4916][4917][4918][4919][4920][4921] 2010

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“…A linear PLA was synthesized in a similar procedure using L-lactide (5.1 g, 35.4 mmol), di (ethylene glycol) benzyl ether (0.05 g, 0.25 mmol) as an initiator, and two drops of Sn(Oct) 2 . Isolation was conducted with the same procedure as described previously.…”

Section: Synthesis Of Linear-pla (L-pla)mentioning

confidence: 99%

Synthesis and Characterization of Star Poly(ε-caprolactone)-b-Poly(ethylene glycol) and Poly(l-lactide)-b-Poly(ethylene glycol) Copolymers: Evaluation as Drug Delivery Carriers

et al. 2008

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Two types of 32 arm star polymers incorporating amphiphilic block copolymer arms have been synthesized and characterized. The first type, stPCL-PEG 32 , is composed of a polyamidoamine (PAMAM) dendrimer as the core with radiating arms having poly(ε-caprolactone) (PCL) as an inner lipophilic block in the arm and poly(ethylene glycol) (PEG) as an outer hydrophilic block. The second type, stPLA-PEG 32 , is similar but with poly(L-lactide) (PLA) as the inner lipophilic block. Characterization with SEC, 1 H NMR, FTIR, and DSC confirmed the structure of the polymers. Micelle formation by both star copolymers was studied by fluorescence spectroscopy. The stPCL-PEG 32 polymer exhibited unimolecular micelle behavior. It was capable of solubilizing hydrophobic molecules, such as pyrene, in aqueous solution, while not displaying a critical micelle concentration. In contrast, the association behavior of stPLA-PEG 32 in aqueous solution was characterized by an apparent critical micelle concentration of ca. 0.01 mg/mL. The hydrophobic anticancer drug etoposide can be encapsulated in the micelles formed from both polymers. Overall, the stPCL-PEG 32 polymer exhibited a higher etoposide loading capacity (up to 7.8 w/w % versus 4.3 w/w % for stPLA-PEG 32 ) as well as facile release kinetics and is more suitable as a potential drug delivery carrier.

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Nano-engineering block copolymer aggregates for drug delivery

Cited by 1,321 publications

References 93 publications

Poly(ethylene glycol)-Block-Poly(2-methyl-2-benzoxycarbonyl-propylene Carbonate) Micelles for Rapamycin Delivery: In Vitro Characterization and Biodistribution

Poly(ethylene glycol)-Block-Poly(2-methyl-2-benzoxycarbonyl-propylene Carbonate) Micelles for Rapamycin Delivery: In Vitro Characterization and Biodistribution

Hierarchically organized micellization of thermoresponsive rod‐coil copolymers based on poly[oligo(ethylene glycol) methacrylate] and poly(ε‐caprolactone)

Synthesis and Characterization of Star Poly(ε-caprolactone)-b-Poly(ethylene glycol) and Poly(l-lactide)-b-Poly(ethylene glycol) Copolymers: Evaluation as Drug Delivery Carriers

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