Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with D,L-lactide/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior

Niwa, Toshiyuki; Takeuchi, Hirofumi; Hino, Tomoaki; Kunou, Noriyuki; Kawashima, Yasunaru

doi:10.1016/0168-3659(93)90097-o

Cited by 432 publications

(210 citation statements)

References 12 publications

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“…Similar to solvent extraction of microsphere particle preparations reviewed by Freitas et al [28] and other nanoparticle formulations [29] this nanoprecipitation method involves dissolving PLGA in a water miscible solvent, such as acetone, and addition to a stabilizing surfactant solution. Briefly, a 1 ml solution of 25 mg/ml PLGA in acetone was added dropwise to 6ml of F68 pluronic surfactant under vortexing.…”

Section: Conjugation Of Glucose Oxidase To Anti-tm and Polymer Beadsmentioning

confidence: 99%

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium

Shuvaev

Christofidou‐Solomidou

Scherpereel

et al. 2007

Journal of Controlled Release

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Vascular drug targeting may improve therapies, yet a thorough understanding of the factors that regulate effects of drugs directed to the endothelium is needed to translate this approach into the clinical domain. To define factors modulating the efficacy and effects of endothelial targeting, we used a model enzyme (glucose oxidase, GOX) coupled with monoclonal antibodies (anti-TM 34 or anti-TM 201 ) to distinct epitopes of thrombomodulin, a surface determinant enriched in the pulmonary endothelium. GOX delivery results in conversion of glucose and oxygen into H 2 O 2 leading to lung damage, a clear physiologic endpoint. Results of in vivo studies in mice showed that the efficiency of cargo delivery and its effect are influenced by a number of factors including: 1) The level of pulmonary uptake of the targeting antibody (anti-TM 201 was more efficient than anti-TM 34 ); 2) The amount of an active drug delivered to the target; 3) The amount of target antigen on the endothelium (animals with suppressed TM levels showed less targeting); and, 4) The substrate availability for the enzyme cargo in the target tissue (hyperoxia augmented GOX-induced injury). Therefore, both activity of the conjugates and biological factors control targeting and effects of enzymatic cargo. Understanding the nature of such "modulating biological factors" will hopefully allow optimization and ultimately applications of drug targeting for "individualized" pharmacotherapy.

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Section: Conjugation Of Glucose Oxidase To Anti-tm and Polymer Beadsmentioning

confidence: 99%

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium

Shuvaev

Christofidou‐Solomidou

Scherpereel

et al. 2007

Journal of Controlled Release

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“…In a modified version of the solvent evaporation method [81][82][83] to produce the precipitation of the polymer and the consequent formation of nanoparticles, it is necessary to promote the diffusion of the solvent of the dispersed phase by dilution with an excess of water when the organic solvent is partly miscible with water or with another organic solvent in the opposite case. Subsequently, the polymer-water saturated solvent phase is emulsified in an aqueous solution containing stabilizer, leading to solvent diffusion to the external phase and the formation of nanospheres or nanocapsules, according to the oil-to-polymer ratio.…”

Section: Emulsification/solvent Diffusion (Esd)mentioning

confidence: 99%

Drug Delivery to The Brain Using Polymeric Nanoparticles: A Review

Bhatt¹,

Ganesh²,

Kothiyal³

2013

Int. J. Pharma Life Sci.

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Nanoparticle drug carriers consist of solid biodegradable particles in size ranging from 10 to 1000 nm (50-300 nm generally). The use of minute particles as drug carriers for targeted treatment has been studied over a long period of time. A selective accumulation of active substances in target tissues has been demonstrated for certain so-called nanocarrier systems that are administered bound to pharmaceutical drugs. Great expectations are placed on nanocarrier systems that can overcome natural barriers such as the blood-brain barrier (BBB) and transport the medication directly to the desired tissue and thus heal neurological diseases that were formerly incurable. Polymeric Nanoparticle have been shown to be promising carriers for CNS drug delivery due to their potential both in encapsulating drugs, hence protecting them from excretion and metabolism, and in delivering active agents across the blood -brain barrier without inflicting any damage to the barrier. Different polymers have been used and different strategies like surface modification have been done to increase the retention time of nanoparticles.

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“…Often, a water insoluble moiety (e.g., a drug or a dye), needs to be encapsulated into a carrier polymer and protected by an emulsifying agent, which also makes the NP water soluble. In particular, the so-called nanoprecipitation method permits preparation of nearly monodisperse NPs in a very simple and reproducible way [5]. Typically, an organic phase, which is usually a dilute polymer solution, e.g., polycaprolactone (PCL) in acetone, plus the hydrophobic moiety to be encapsulated, e.g., a drug or a fluorescent dye, is injected by pressure into an aqueous solution of the emulsifying agent, Fig.…”

mentioning

confidence: 99%

Controlled Nanoparticle Formation by Diffusion Limited Coalescence

et al. 2012

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Polymeric nanoparticles (NPs) have great application potential in science and technology. Their functionality strongly depends on their size. We present a theory for the size of NPs formed by precipitation of polymers into a bad solvent in the presence of a stabilizing surfactant. The analytical theory is based upon diffusion-limited coalescence kinetics of the polymers. Two relevant time scales, a mixing and a coalescence time, are identified and their ratio is shown to determine the final NP diameter. The size is found to scale in a universal manner and is predominantly sensitive to the mixing time and the polymer concentration if the surfactant concentration is sufficiently high. The model predictions are in good agreement with experimental data. Hence the theory provides a solid framework for tailoring NPs with a priori determined size. Polymeric nanoparticles (NPs) are gaining increasing attention because of their numerous applications in, for instance, physics, chemistry and medicine [1]. The NP size and size distribution are the key parameters often determining their functionality. Therefore, one of the main experimental challenges is to prepare NPs with well controlled dimensions tuned for a particular application. Models of NP formation, allowing one to steer the NP preparation process in the right direction, would simplify the size control significantly.A high level of control over particle size is required in, for example, targeted delivery (e.g., oncology). Size influences the circulating half lifetime and is crucial for selective cellular uptake: NPs between 50 and 200 nm in size are desired in passive cancer tumor targeting as they are too large to harm healthy cells but small enough to penetrate into the diseased ones. In brain imaging, fluorescent dye loaded particles of about 100 nm with biocompatible polymer coatings are used because they produce small, sharply defined injection sites and show no toxicity in vivo or in vitro [2][3][4].Although there are several methods for NP preparation, only few of them permit a high level of control on the particle size and the particle size distribution [2]. Often, a water insoluble moiety (e.g., a drug or a dye), needs to be encapsulated into a carrier polymer and protected by an emulsifying agent, which also makes the NP water soluble. In particular, the so-called nanoprecipitation method permits preparation of nearly monodisperse NPs in a very simple and reproducible way [5]. Typically, an organic phase, which is usually a dilute polymer solution, e.g., polycaprolactone (PCL) in acetone, plus the hydrophobic moiety to be encapsulated, e.g., a drug or a fluorescent dye, is injected by pressure into an aqueous solution of the emulsifying agent, Fig. 1(a). As the organic solvent is chosen to be water-miscible, rapid quenching (towards poor solvent conditions) of the hydrophobic polymer and the drug in water takes place. This results in coalescence of the polymer and the drug into submicron particles decorated by surfactant [2,6]. Alternatively, a block copo...

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Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with D,L-lactide/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior

Cited by 432 publications

References 12 publications

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium

Drug Delivery to The Brain Using Polymeric Nanoparticles: A Review

Controlled Nanoparticle Formation by Diffusion Limited Coalescence

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