Sparged Animal Cell Bioreactors: Mechanism of Cell Damage and Pluronic F‐68 Protection

Murhammer, David W.; Goochee, Charles F.

doi:10.1021/bp00005a012

Cited by 170 publications

(92 citation statements)

References 33 publications

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“…1 These have an extensive range of applications in the medical field such as drug solubilization, controlled drug release. [2][3][4] Moreover, Pluronic have recently attracted a great deal of attention as excellent membrane sealants with low toxicity. [5][6][7] Of particular interest is poloxamer 188 (Pluronic F68), an approximately 8400 g/mol poloxamer of the form PEO 76 -PPO 29 -PEO 76 that has been proven as a surfactant sealing agent for permeabilized lipid bilayers.…”

Section: Introductionmentioning

confidence: 99%

Effects of pluronic F68 micellization on the viability of neuronal cells in culture

Samith

Mino

Ramos-Moore

et al. 2013

J of Applied Polymer Sci

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Triblock copolymers with surface-active properties, referred to as Pluronic, have shown potential medical applications such as drug delivery to selective targets in the human body. In particular, the transport of anti-inflammatory substances to the brain is required for illness treatment, thus the study of delivery agents that cross the blood-brain barrier is relevant. In this article we study the effects of the micelle formation on the morphologic and cytotoxic properties of Pluronic F68. We determinate the critical micellar concentration (CMC) by standard tensiometric and absorbance measurements, and also we analyze the morphology of polymers by atomic force microscopy. Our observations indicate that the morphological properties of F68 are drastically modified in the CMC range, as well as the ability to increase the viability of neuroblastoma cells maintained under culture conditions, as compared with nontreated cells. Our conclusions highlight the close correlation between morphological and physiochemical properties of Pluronic, which must be further understood in order to achieve highly controlled pharmacological uses.

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Section: Introductionmentioning

confidence: 99%

Effects of pluronic F68 micellization on the viability of neuronal cells in culture

Samith

Mino

Ramos-Moore

et al. 2013

J of Applied Polymer Sci

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“…The study of agitation rate without sparged aeration is usually inconclusive due to bubble entrainment at high agitation rates before a low Kolmogoroff eddy size is reached (Murhammer and Goochee, 1990). In this work, the determination of the critical agitation rate at a reasonably high aeration rate and the determination of the critical aeration rate under conditions of gas dispersion and turbulence based on cell growth parameters allowed an efficient optimization Figure 5.…”

Section: Discussionmentioning

confidence: 92%

Optimization of the production of virus-like particles in insect cells

Cruz

Cunha

Peixoto

et al. 1998

Biotechnol. Bioeng.

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In this work the maximal operational hydrodynamic conditions (agitation and aeration rate) that cause no adverse effect in Sf‐9 cells growth in SF900II serum‐free medium were determined. Shear stresses higher than 1 N m−2 and aeration rates higher than 0.04 vvm affect cell growth and when these conditions increase to 1.5 N m−2 and 0.11 vvm, cell growth is completely inhibited with significant cell morphology changes and a strong decrease in viability. Although the pO2 did not show a significant effect upon cell growth in the range from 10 to 50%, cell infection and specific productivity were dramatically affected. The production was optimal at a pO2 of 25% with decreases higher than 50% being observed when the pO2 decreased to 10 or increased to 50%. The maximum product quality, i.e., the percentage of product in the form of high molecular weight particles, is not coincident with maximum product titer. Although the highest Pr55gag particle titer was obtained at 96 hours post infection (hpi) and at pO2 of 25%, the best product quality (defined by gel filtration chromatography and Western immunoblot) was obtained at 48 hpi, independently of the pO2 used. The effect of overcritical conditions upon productivity was also studied. As obtained for cell growth, cell infection is affected by shear stresses above 1 N m−2 and by aeration rates higher than 0.04 vvm, with decreases in Pr55gag particle titer higher than 70%, even when the overcritical values are still far from the limit at which cell death occurs. The results obtained and the optimization strategy used allowed the maximization of the oxygen supply without damaging the cells, with important consequences on the scale‐up of a production process involving this insect cell/baculovirus expression system. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 60: 408–418, 1998.

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“…15,16 Pluronic P85 (PEO 26 PPO 40 PEO 26 ) has the ability to inhibit various transporters, such as breast cancerresistant protein, multidrug resistance protein 2 (MDR 2 ), and P-glycoprotein (Pgp, also known as MDR 1 ), thereby enhancing the cellular accumulation of anticancer and other drugs that are normally excluded from cells by these transporters. 17 Pluronic F127 (PEO 100 PPO 65 PEO 100 ), or poloxamer 407, easily forms micelles and has been used as an efficient carrier for various hydrophobic drugs.…”

Section: Introductionmentioning

confidence: 99%

Differentiation of human stem cells is promoted by amphiphilic pluronic block copolymers

Doğan¹,

Yalvaç²,

Şahın³

et al. 2012

IJN

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Stem cell usage provides novel avenues of tissue regeneration and therapeutics across disciplines. Apart from ethical considerations, the selection and amplification of donor stem cells remain a challenge. Various biopolymers with a wide range of properties have been used extensively to deliver biomolecules such as drugs, growth factors and nucleic acids, as well as to provide biomimetic surface for cellular adhesion. Using human tooth germ stem cells with high proliferation and transformation capacity, we have investigated a range of biopolymers to assess their potential for tissue engineering. Tolerability, toxicity, and their ability to direct differentiation were evaluated. The majority of pluronics, consisting of both hydrophilic and hydrophobic poly(ethylene oxide) chains, either exerted cytotoxicity or had no significant effect on human tooth germ stem cells; whereas F68 increased the multi-potency of stem cells, and efficiently transformed them into osteogenic, chondrogenic, and adipogenic tissues. The data suggest that differentiation and maturation of stem cells can be promoted by selecting the appropriate mechanical and chemical properties of polymers. It has been shown for the first time that F68, with its unique molecular characteristics, has a great potential to increase the differentiation of cells, which may lead to the development of new tissue engineering strategies in regenerative medicine.

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Sparged Animal Cell Bioreactors: Mechanism of Cell Damage and Pluronic F‐68 Protection

Cited by 170 publications

References 33 publications

Effects of pluronic F68 micellization on the viability of neuronal cells in culture

Effects of pluronic F68 micellization on the viability of neuronal cells in culture

Optimization of the production of virus-like particles in insect cells

Differentiation of human stem cells is promoted by amphiphilic pluronic block copolymers

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