New Synthetic Amphiphilic Polymers for Steric Protection of Liposomes in Vivo

Torchilin, Vladimir P.; Trubetskoy, Vladimir S.; Whiteman, Kathleen R.; Caliceti, Paolo; Ferruti, Paolo; Veronese, Francesco M.

doi:10.1002/jps.2600840904

Cited by 162 publications

(98 citation statements)

References 27 publications

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“…Since GLUTs can facilitate the glucose transport from the blood to the brain, glucose analogs should be good candidates for drug transport through the BBB. 15,16 In previous studies, different glycol-conjugates as candidates for the treatment of CNS diseases have been synthesized, which could increase BBB permeability through the affinity with GLUT1, such as dopamine, 17,18 glycosyl-derivatives of ibuprofen, 19 among others. Besides the prodrugs, glucose-modified liposomes using ethylene glycols with short chain length as the linkers have also been investigated.…”

Section: Introductionmentioning

confidence: 99%

Investigation of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers for brain targeting

Xie

Yao²,

Qin³

et al. 2012

IJN

111

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Background An intimidating challenge to transporting drugs into the brain parenchyma is the presence of the blood–brain barrier (BBB). Glucose is an essential nutritional substance for brain function sustenance, which cannot be synthesized by the brain. Its transport primarily depends on the glucose transporters on the brain capillary endothelial cells. In this paper, the brain-targeted properties of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers were compared and evaluated to establish an optimized drug-delivery system. Methods Coumarin 6-loaded liposomes (GLU200-LIP, GLU400-LIP, GLU1000-LIP, and GLU2000-LIP) composed of phospholipids and glucose-derived cholesterols were prepared by thin-film dispersion-ultrasound method. The BBB model in vitro was developed to evaluate the transendothelial ability of the different liposomes crossing the BBB. The biodistribution of liposomes in the mice brains was identified by in vivo and ex vivo nearinfrared fluorescence imaging and confocal laser scanning microscopy and further analyzed quantitatively by high-performance liquid chromatography. Results Glucose-derived cholesterols were synthesized and identified, and coumarin 6-loaded liposomes were prepared successfully. The particle sizes of the four types of glucose-modified liposomes were around or smaller than 100 nm with a polydispersity index less than 0.300. GLU400-LIP, GLU1000-LIP, and GLU2000-LIP achieved higher cumulative cleared volumes on BBB model in vitro after 6 hours compared with GLU200-LIP ( P < 0.05) and were significantly higher than that of the conventional liposome ( P < 0.001). The qualitative and quantitative biodistribution results in the mice showed that the accumulation of GLU1000-LIP in the brain was the highest among all the groups ( P < 0.01 versus LIP). Conclusion The data indicated that GLU400-LIP, GLU1000-LIP, and GLU2000-LIP all possess the potential of brain targeting, among which GLU1000-LIP, as a promising drug-delivery system, exhibited the strongest brain delivery capacity.

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Section: Introductionmentioning

confidence: 99%

Investigation of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers for brain targeting

Xie

Yao²,

Qin³

et al. 2012

IJN

111

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“…N-Acryloylmorpholine was used for many years to synthesize cross-linked networks for gel-phase synthesis of peptides, [16 -18] semi-permeable membranes for plasma separation, [20 -22] polymeric supports for gel chromatography [23] and capillary electrophoresis. [24] Linear poly(Nacryloylmorpholine) was also used for drug delivery applications, protecting liposomes from blood clearance, [25] or increasing the lifetime of enzymes both in vitro and in vivo. [26] N-acryloylmorpholine was homopolymerized in the presence of a chain transfer agent to give end-functionalized low molecular weight oligomers, [27,28] and copolymerized forming a linear copolymer [8] or a graft copolymer.…”

Section: Introductionmentioning

confidence: 99%

Kinetic Study of Free-Radical Solution Copoly- merization ofN-Acryloylmorpholine with an Activated Ester-Type Monomer,N-Acryloxysuccinimide

D’Agosto

Charreyre

Véron

et al. 2001

Macromol. Chem. Phys.

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The kinetics of free radical solution (co)polymerization of N‐acryloylmorpholine (NAM) and N‐acryloxysuccinimide (NAS) have been investigated at 60°C in 1,4‐dioxane using 2,2′‐azoisobutyronitrile as the initiator. First, the kp/kt1/2 value for the homopolymerization of NAM monomer was estimated to be 4.97 mol–1/2·L1/2· s–1/2, which is indicative of a high ability of NAM to homopolymerize. Then, the reactivity ratios were determined to be rNAS = 0.63 ± 0.03 and rNAM = 0.75 ± 0.01. This binary comonomer system behaves like a perfectly random one, allowing the synthesis of macromolecules homogeneous in composition. Average copolymer compositions determined by 1H NMR and 13C NMR spectroscopy were in good agreement with the theoretical ones. Finally, monomer sequence distribution was studied by 13C NMR analysis.

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“…15 Some other hydrophilic polymers may be used as hydrophilic blocks. 16 Among possible alternatives to PEO, poly(N-vinyl-2-pyrrolidone) (PVP), which is highly biocompatible 17 and could be employed in diblock polymer micelles, 18 polyvinyl alcohol (PVA), and poly(vinyl alcohol-co vinyl oleate) co-polymer, which was used to prepare micelles enhancing transcutaneous permeation of retinyl palmitate, have been proposed. 19 PVA substituted with oleic acid has also been used for carrying lipophilic drugs.…”

Section: Passive Targetingmentioning

confidence: 99%

Receptor binding peptides for target-selective delivery of nanoparticles encapsulated drugs

Accardo¹,

Aloj²,

Aurilio³

et al. 2014

IJN

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Active targeting by means of drug encapsulated nanoparticles decorated with targeting bioactive moieties represents the next frontier in drug delivery; it reduces drug side effects and increases the therapeutic index. Peptides, based on their chemical and biological properties, could have a prevalent role to direct drug encapsulated nanoparticles, such as liposomes, micelles, or hard nanoparticles, toward the tumor tissues. A considerable number of molecular targets for peptides are either exclusively expressed or overexpressed on both cancer vasculature and cancer cells. They can be classified into three wide categories: integrins; growth factor receptors (GFRs); and G-protein coupled receptors (GPCRs). Therapeutic agents based on nanovectors decorated with peptides targeting membrane receptors belonging to the GPCR family overexpressed by cancer cells are reviewed in this article. The most studied targeting membrane receptors are considered: somatostatin receptors; cholecystokinin receptors; receptors associated with the Bombesin like peptides family; luteinizing hormone-releasing hormone receptors; and neurotensin receptors. Nanovectors of different sizes and shapes (micelles, liposomes, or hard nanoparticles) loaded with doxorubicin or other cytotoxic drugs and externally functionalized with natural or synthetic peptides are able to target the overexpressed receptors and are described based on their formulation and in vitro and in vivo behaviors

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New Synthetic Amphiphilic Polymers for Steric Protection of Liposomes in Vivo

Cited by 162 publications

References 27 publications

Investigation of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers for brain targeting

Investigation of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers for brain targeting

Kinetic Study of Free-Radical Solution Copoly- merization ofN-Acryloylmorpholine with an Activated Ester-Type Monomer,N-Acryloxysuccinimide

Receptor binding peptides for target-selective delivery of nanoparticles encapsulated drugs

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