Nanosuspensions in drug delivery

Rabinow, Barrett

doi:10.1038/nrd1494

Cited by 1,350 publications

(810 citation statements)

References 73 publications

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“…In contrast, nanosuspensions carrying submicron-sized crystalline drug particles that are stabilized by coatings of surfactant to produce stable pharmaceutical formulations. 34 The drug loaded into nanoparticles may not dissolve readily upon intravenous administration and may be phagocytosed by Kupffer cells and resident macrophages in the liver and spleen. Furthermore, the drug crystals will slowly dissolve and then diffused out of the cells into the extracellular space.…”

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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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%

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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“…An important fraction (40%) of the new drug candidates emerging from drug discovery programs has poor water solubility and this trend is not expected to change in the future [1,2]. The aqueous solubility of a drug is a prime determinant of its dissolution rate.…”

Section: Introductionmentioning

confidence: 99%

“…with cyclodextrins) and the molecular dispersion of the drug in a hydrophilic polymer matrix [6]. A simpler and more versatile strategy to improve dissolution is to reduce the particle size down to the nanometer size range, and thereby enlarge substantially the specific surface area [2,[5][6][7]. Nanonization may be achieved either through precipitation of dissolved molecules (bottom-up approach) or comminution of larger particles (top-down approach).…”

Section: Introductionmentioning

confidence: 99%

Nanonization of megestrol acetate by laser fragmentation in aqueous milieu

Sylvestre

Tang

Fürtös

et al. 2011

Journal of Controlled Release

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Nanonization is a simple and effective method to improve dissolution rate and oral bioavailability of drugs with poor water solubility. There is growing interest to downscale the nanocrystal production to enable early preclinical evaluation of new drug candidates when compound availability is scarce. The purpose of the present study was to investigate laser fragmentation to form nanosuspensions in aqueous solution of the insoluble model drug megestrol acetate (MA) using very little quantities of the drug. Laser fragmentation was obtained by focusing a femtosecond (fs) or nanosecond (ns) laser radiation on a magnetically stirred MA suspension in water or aqueous solution of a stabilizing agent. The size distribution and physicochemical properties of the drug nanoparticles were characterized, and the in vitro dissolution and in vivo oral pharmacokinetics of a laser fragmented formulation were evaluated. A MA nanosuspension was also prepared by media milling for comparison purpose. For both laser radiations, smaller particles were obtained as the laser power was increased, but at a cost of higher degradation. Significant nanonization was achieved after a 30-min fs laser treatment at 250 mW and a 1-h ns laser treatment at 2500 mW. The degradation induced by the laser process of the drug was primarily oxidative in nature. The crystal phase of the drug was maintained, although partial loss of crystallinity was observed. The in vitro dissolution rate and in vivo bioavailability of the laser fragmented formulation were similar to those obtained with the nanosuspension prepared by media milling, and significantly improved compared to the coarse drug powder. It follows that this laser nanonization method has potential to be used for the preclinical evaluation of new drug candidates.

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“…Drug nanosuspensions represent crystalline drug particles often stabilized by non-ionic PEGcontaining surfactants or with mixtures of lipids [203,204]. They can be manufactured by a variety of techniques such as media milling, high-pressure homogenization or using emulsions and microemulsions as templates [205,206].…”

Section: Nanoparticlesmentioning

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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Nanosuspensions in drug delivery

Cited by 1,350 publications

References 73 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

Nanonization of megestrol acetate by laser fragmentation in aqueous milieu

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

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