PEG–PLA nanoparticles prepared by emulsion solvent diffusion using oil-soluble and water-soluble PEG–PLA

Muranaka, Makoto; Hirota, Ken; Ono, Tsutomu

doi:10.1016/j.matlet.2010.01.076

Cited by 14 publications

(9 citation statements)

References 14 publications

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“…In order to prepare impurity-free biocompatible microspheres, we have used amphiphilic water-soluble PEG-b-PLA (w-PEG-PLA). 15 The PEG segment is hydrophilic and biocompatible, while, in contrast, the PLA segment is hydrophobic. Moreover, EA is a good solvent for only the PLA segment, though DCM solves both PEG and PLA segments.…”

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confidence: 99%

“…For these reasons, w-PEG-PLA plays a role of a surfactant in the EA/water emulsion system. 15 Eventually, a monodisperse O/W emulsion prepared by a microfluidic emulsification is simply poured into an excess amount of water, and which accelerates solvent diffusion from the oil droplets into the water and then solidifies the microspheres. This simple ''dilution'' process enables rapid and continuous production of micron-sized monodisperse PLA microspheres from emulsion at ordinary temperatures and pressures.…”

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Continuous fabrication of monodisperse polylactide microspheres by droplet-to-particle technology using microfluidic emulsification and emulsion–solvent diffusion

2011

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Monodisperse polylactide (PLA) microspheres were continuously fabricated by microfluidic emulsification and subsequent dilution into water. The diameter was precisely tuned from 6 to 50 µm by changing the flow rate of the fluids in microfluidics or the PLA concentration in the dispersed phase. The use of amphiphilic oil-soluble poly(ethylene glycol)-b-polylactide (o-PEG-PLA) as a matrix resulted in a highly porous microsphere morphology, and the porosity was controlled by blending PLA. Therefore, monodisperse PLA microspheres with the predetermined surface porosity were continuously produced by just enough reagents and energy. Biodegradable polymeric microspheres have been developed for use in the chemical industry such as in coatings, inks, agrichemicals, foods, and drug delivery carriers. 1-3 In particular, polylactide (PLA) has attracted a great deal of attention all over the world in recent decades because it is producible from renewable resources. PLA is also well known for its biodegradability and biocompatibility. It breaks down into lactic acid units that are nontoxic to the human body. In general, PLA microspheres are prepared by the emulsion-solvent evaporation technique. 4-6 However, this technique has drawbacks such as the presence of toxic solvent residues in the end products, requirement for multi-step preparation, and polydispersity in the microsphere diameter. During emulsion preparation, although dichloromethane (DCM) is commonly used as the organic solvent because of good solubility of PLA and its high volatility, which facilitates easy evaporation from the emulsion droplets, it is harmful to human health so that complete removal of it from the products is required. Surfactants used for emulsification also should be eliminated because of these were non-essentials of human body. Multi-step preparation of microspheres results in greater equipment investment and the total production cost. Moreover, monodispersity in microsphere diameter enhances the quality of final products in all applications and saves further separation processes. In drug delivery applications, for example, monodisperse carriers decrease undesirable side effects and achieve precise control of drug release kinetics and encapsulation efficiency. In recent years, preparation methods for monodisperse microspheres have been developed. For example,

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Continuous fabrication of monodisperse polylactide microspheres by droplet-to-particle technology using microfluidic emulsification and emulsion–solvent diffusion

2011

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“…In this study, we used two different PEG-PLA block copolymers with different PLA segment lengths. 30) One was a water-soluble PEG-PLA (Mw: 6000 (PEG 5000; PLA 1000), hydrophile-lipophile balance (HLB)= 15.65) to stabilize emulsion droplets without any undesirable residue. The other was oil-soluble PEG-PLA (Mw: 42000 (PEG 5000; PLA 37000), HLB= 2.65) for a resultant nanoparticle component.…”

Section: Methodsmentioning

confidence: 99%

“…30) PTX (1 mg) and oil-soluble PEG-PLA (40 mg) were dissolved in 4 mL of ethyl acetate with tracer amounts of 3 H-CHE and 14 C-PTX. The polymer solution was mixed with 8 mL of aqueous solution dissolved water-soluble PEG-PLA (420 mg), followed by sonication emulsification for 5 min at room temperature using a probe-type sonicator (50 W, Ohtake Works, Tokyo).…”

Section: Methodsmentioning

confidence: 99%

Formulation and Evaluation of Paclitaxel-Loaded Polymeric Nanoparticles Composed of Polyethylene Glycol and Polylactic Acid Block Copolymer

Araki

Kono

Ogawara

et al. 2012

Biological & Pharmaceutical Bulletin

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To develop potent paclitaxel (PTX) formulations for cancer chemotherapy, we formulated PTX into polymeric nanoparticles composed of polyethylene glycol (PEG) and polylactic acid (PLA) block copolymer (PN-PTX). First, the physicochemical properties of PN-PTX prepared were assessed; the mean particle size was around 80 nm and the zeta potential was found to be almost neutral. Next, the in vitro PTX release property was assessed by a dialysis method. Although rapid release of PTX was observed just after dosing, around 70% of PTX was stably incorporated in polymeric nanoparticles for a long time in the presence of serum. Then, the in vivo pharmacokinetics of PN-PTX after intravenous administration was investigated in Colon-26 (C26) tumor-bearing mice. Both polymeric nanoparticles and PTX incorporated exhibited a long blood circulating property, leading to enhanced permeability and retention (EPR) effect-driven, time-dependent tumor disposition of PTX. Tumor distribution increased gradually for 24 h, and tissue uptake clearance of polymeric nanoparticles in the liver and spleen was lower than that of PEG liposomes. Since these results indicated that the in vivo disposition characteristics of PN-PTX were very favorable, we then evaluated the anti-tumor effect of PN-PTX in C26 tumor-bearing mice. However, PN-PTX did not exhibit any significant anti-tumor effect, presumably due to the poor PTX release from polymeric nanoparticles. From these results, it is considered that the favorable pharmacokinetic properties of nanoparticles and the drug incorporated do not always lead to its potent in vivo pharmacological activity, suggesting the importance of PTX release properties within tumor tissues.Key words paclitaxel; block-copolymer; nanoparticle; enhanced permeability and retention effect Paclitaxel (PTX) belongs to the taxane family of anti-cancer agents, and has been demonstrated to exert good clinical anticancer efficacy in various cancers including ovarian, breast, head and neck, and non-small cell lung cancers.1) Due to its poor aqueous solubility, the commercially available product for intravenous infusion of PTX, known as Taxol ® , formulates PTX in a 1 : 1 mixture of Cremophor EL (polyethoxylated castor oil) and ethanol. However, Cremophor EL has been considered to be associated with severe adverse effects such as hypersensitivity, neurotoxicity, and nephropathia. Premedication with corticosteroids and antihistamines is therefore used to reduce the intensity and incidence of these side effects. 2,3)Since these problems associated with the current PTX formulation are mainly ascribed to the poor aqueous solubility and non-specific in vivo disposition characteristics of PTX, a lot of attention has been paid to developing a safer PTX dosage form with higher PTX solubilizing capability and better tumor targeting properties while reducing non-specific disposition to other tissues/organs. Various nanoparticulate PTX formulations such as lipid nanoparticles, 4) polymeric micelles, 5-8) liposomes 9-13) and emulsions [14][15...

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“…To date, PEG-b-PLA nanoparticles have been generally prepared by either emulsion-solvent evaporation method [14][15][16][17][18] or emulsion-solvent diffusion method [19][20][21][22][23][24]. Both of these nanoparticle-forming processes, however, are based on the removal of organic solvent from the precursor emulsion droplets in which the PEG-b-PLA nanoparticles and the drugs are dissolved.…”

Section: Introductionmentioning

confidence: 99%

Indocyanine green-laden poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanocapsules incorporating reverse micelles: Effects of PEG-b-PLA composition on the nanocapsule diameter and encapsulation efficiency

Watanabe

Sakamoto

Inooka

et al. 2017

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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Reverse micelles are thermodynamically stable systems, with a capacity to encapsulate hydrophilic molecules in their nanosized core, which is smaller than the core generally obtained with water-in-oil-emulsion droplets. Herein, we present a simple technique for the preparation of poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanocapsules encapsulating a hydrophilic photosensitizer (indocyanine green, ICG), which exploits reverse micelle formation and subsequent emulsion-solvent diffusion. We establish the effect of the PEG-b-PLA composition and the co-surfactant volume on the diameter and water content of the reverse micelles. We demonstrate that the composition of PEG-b-PLA affects also the diameter and encapsulation efficiency of the resulting nanocapsules. We show that the ICG-laden nanocapsules fabricated under the most optimal conditions have a diameter of approximately 100 nm and an ICG encapsulation 3 efficiency of 58%. We believe that the method proposed here is a promising step towards the preparation of hydrophilic drug-laden polymer nanocapsules with a small diameter and therefore suitable for use in drug delivery applications based on enhanced permeability and retention (EPR) effect-driven passive targeting.

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PEG–PLA nanoparticles prepared by emulsion solvent diffusion using oil-soluble and water-soluble PEG–PLA

Cited by 14 publications

References 14 publications

Continuous fabrication of monodisperse polylactide microspheres by droplet-to-particle technology using microfluidic emulsification and emulsion–solvent diffusion

Continuous fabrication of monodisperse polylactide microspheres by droplet-to-particle technology using microfluidic emulsification and emulsion–solvent diffusion

Formulation and Evaluation of Paclitaxel-Loaded Polymeric Nanoparticles Composed of Polyethylene Glycol and Polylactic Acid Block Copolymer

Indocyanine green-laden poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanocapsules incorporating reverse micelles: Effects of PEG-b-PLA composition on the nanocapsule diameter and encapsulation efficiency

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