Versatile Poloxamer 188 - Serving as a Cell Shear Protectant
Time：2024-03-25 Hits：153
I. Cell Shear Protectant Application
Background
With the constant development of modern biological science research, traditional cell shake flasks and cell factories are no longer sufficient to cater to the demands of small-scale semi-production capacity cell culture. The utilization of bioreactors for large-scale cell expansion has gradually emerged as the primary solution to this challenge. Nevertheless, during cell culture in stirred bioreactors, cellular damage is inevitable. This damage primarily stems from two sources:
The introduction of diverse gases into the culture system is necessary to maintain the partial pressure of DO and CO2 within the reactor. However, when these bubbles ascend to the surface of the culture medium and burst, they inflict significant harm to the cells.
The turbulent shear force generated by the stirring mechanism within the reactor also poses a threat to the cells. So, is there a protective agent that can mitigate this cellular damage? poloxamer P188 finds widespread application as a shear protectant in cell culture. It shields cells from the turbulent environment within the bioreactor and exhibits a notable effect in preventing cells from hydrodynamic damage. Typically, poloxamer P188 is used in concentrations ranging from 0.5 to 3.0g/L in cell culture media. Reports indicate that even increasing the concentration to 5g/L does not compromise cell culture performance or product quality. While the exact mechanism of poloxamer P188's protective function remains debatable, most experiments suggest that it may reduce cell attachment to bubbles or alter the fluidity of the cell membrane [1].
Application Mechanism
Why does Poloxamer P188 Mitigate Cell Damage Caused by Turbulent Shear Force?
Poloxamers are triblock copolymers composed of a hydrophobic polypropylene oxide (PPO) core sandwiched between two hydrophilic polyethylene oxide (PEO) chains. Their unique structure allows them to interact with both hydrophilic and hydrophobic environments, making them highly versatile surfactants.
Within the poloxamer family, there are over 50 members, each with distinct molecular weights ranging from 1,600 to 14,600 Da and varying percentages of PPO, ranging from 15% to 86%. These differences account for their varying physicochemical properties, such as their physical state (liquid, paste, or solid) at room temperature. Since their discovery in the 1950s, poloxamers have become an essential class of nonionic polymeric surfactants, finding diverse industrial applications.
Poloxamer P188 stands out as one of the most commonly used poloxamer products. With an average molecular weight of 8400Da and a PEO content of approximately 80%, it is known by various brand names such as PluronicVR F68, LutrolVR F68, and Kolliphor VR P188. Its high hydrophilic-lipophilic balance (HLB) value allows it to effectively reduce surface tension to approximately 50dyn/cm in a 0.1% aqueous solution at room temperature [1].
Seebio® P188 non-ionic surfactant, a formulated 10% concentrate that is endotoxin-tested, exhibits an HLB value of approximately 29. In a 0.1% aqueous solution, it can reduce surface tension to around 50 dyn/cm at room temperature. This product finds its application in cell culture media, where it shields cells from the deleterious effects of hydrodynamic forces and minimizes fluid shear stress damage. Additionally, it can be employed to mitigate foam formation during suspension stirring culture and reduce cell adhesion to the reactor tank wall.
Product Information:
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Item number
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product name
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Packaging
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DCH0535A-50ml
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Seebio® P188 Nonionic Surfactant (100×)
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50ml
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Product parameters：
Culture testing (CHO-K1)：pass
Endotoxin：Depend on COA
Sterility Testing：Negative
II. As a Pharmaceutical Excipient
In addition to serving as a shear protectant in cell culture, Poloxamer 188 is also a widely used polymer excipient. As a nonionic surfactant, it possesses remarkable emulsifying capabilities and safety profiles, making it a valuable addition to pharmaceuticals and medicinal products.
In Pharmaceuticals:
1. As an Emulsifier
Poloxamer stands as the sole synthetic emulsifier currently employed in intravenous emulsions. Amongst its varieties, Poloxamer 188 exhibits the finest emulsifying performance and safety characteristics. It functions as an oil-in-water (O/W) emulsifier, typically employed at a concentration of 0.3% [3].
2. As a Solubilizing Agent
As a nonionic surfactant, Poloxamer 188 enhances the solubility of poorly soluble drugs by forming micelles. Furthermore, it finds applications in phytochemistry. Research demonstrates that Poloxamer 188 effectively solubilizes fat-soluble allelochemicals like ferulic acid and vanillin. Within a safe concentration range, these compounds can be fully dissolved in water, forming a stable system that remains unchanged during experiments, thus facilitating accurate and quantitative studies of allelopathic activities. Additionally, due to its high safety profile, Poloxamer 188 does not adversely affect recipient plants within a broad concentration range, thus avoiding false positive results that may arise from the use of co-solvents during testing [4].
3. Enhancing Drug Dissolution
In its solid form, Poloxamer 188 can be utilized as a carrier for solid dispersions. Within these dispersions, it improves the wettability of drugs and enhances their intrinsic solubility, ultimately altering their inherent dissolution rates [5].
4. As a Substrate
Poloxamer, with its high molecular weight and hydrophilic properties, serves as a matrix material for various pharmaceutical formulations such as water-soluble suppositories, hydrophilic ointments, gels, and pills. In oral preparations, water-soluble poloxamer primarily functions as a solubilizer and emulsifier. Its ability to enhance the dissolution rate and in vivo absorption of drugs may be attributed to its wetting, solubilizing properties, as well as its ability to slow down gastrointestinal motility and prolong absorption time [2].
5. Role as a Thickening, Dispersing, and Suspending Agent in Liquid Pharmaceuticals
Poloxamer can also be utilized as a precipitating and defoaming agent in protein separation processes.
6. As an Absorption Enhancer
Poloxamer 188 exhibits dual benefits in enhancing drug absorption. Firstly, it slows down intestinal peristalsis, extending the retention time of drugs in the gastrointestinal tract and thereby improving their absorption, which ultimately enhances the bioavailability of oral formulations. Secondly, due to its excellent compatibility with the skin, it increases skin permeability, facilitating the absorption of topical pharmaceutical preparations [6].
In Medical Research
1. Poloxamer 188 can effectively inhibit thrombus formation and prevent skeletal muscle necrosis in adults, offering promising therapeutic benefits [7].
2. Poloxamer 188 in Treating Brain Damage:
Extensive research has demonstrated that poloxamer 188 can significantly reduce inflammation and tissue damage resulting from experimental brain injuries in rats. Furthermore, there is evidence suggesting its neuroprotective effects in other experimental models as well [8,9]. In studies conducted on rats, a single dose of poloxamer 188 was found to combat early neuronal damage after hemorrhage, although it had no significant effect on neuronal damage caused by prolonged hemorrhage. However, with daily administration, poloxamer 188 may provide long-term, effective neuronal protection [10].
Seebio Pharmaceutical Grade Poloxamer 188
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Item number
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Product
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Packaging
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ACH0497B
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Poloxamer 188 pharmaceutical grade
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50ml
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Medicinal poloxamer quality standard reference[2]
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Index
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Chinese Pharmacopoeia 2005 Edition
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United States Pharmacopeia 28th edition
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Average Relative Molecular Weight
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The average molecular weight of 1000 to 7000 should be the labeled amount.90%~110%
Those with average molecular weight above 7000 should be labeled.80%~120%
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7680～9510
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Unsaturation
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0.065±0.035
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0.026±0.008
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Polyoxyethylene
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81.8%±1.9%
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81.8%±1.9%
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Heavy Metal
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Not greater than 20ppm
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Not greater than 20ppm
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Free Ethylene Oxide, Propylene Oxide, Dioxane
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/
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Respectively shall not exceed 1ug/g, 5ug/g, 5ug/g
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Arsenic Salt
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Shall not exceed 0.0002%
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/
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pH
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5.0～7.5
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5.0～7.5
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*Note: Poloxamer 188, as standardized in the Chinese Pharmacopoeia, is suitable only as an oral excipient. Further refinement is necessary for its use as an injection excipient.
参考文献
[1] https://zhuanlan.zhihu.com/p/657726580
[2] Application of poloxamer 188 https://max.book118.com/html/2021/1204/8024041062004051.shtm
[3] Wang Meng, Zhang Junshou, Zhou Jianping. Injection excipient poloxamer 188. Pharmacy Clinical and Research, 2007, 15(1):10-13
[4] Tao Yuehong, Zhang Zhao, Zhang Bengang et al. Application of Poloxamers in the biological detection of fat-soluble allelochemicals. Wuhan Botany Research, 2008, 26(5):533-539
[5] Rina J.Chokshi and Hossein Zia.Improving the Dissolution Rate of Poorly Water Soluble Drug by Solid Dispersion and SolidSolution-Pros and Cons.Drug Delivery, 2007,14:33-45
[6] Wu Gang. Research progress of poloxamer 188. Modern Chinese Doctors, 2008, 46(12):48-49
[7] Wang Hao, Gu Jijin, Deng Yingjie. Research on the preparation of diclofenac sodium submicroemulsion using poloxamer 188 as co-emulsifier. Chinese Pharmacy, 2008, 19(25): 1965-1967
[8] Hitesh R.Patel1,Rakesh P.Patel1,M.M.Patel.Poloxamers:A pharmaceutical excipients with therapeutic behaviors.International Journal of PharmTech Research,2009,11(2):299-303,
[9] John M.Collins,Florin Despa,Paphael C.Lee.Structuraland Functional Recovery of Electropermeabilized SkeletalMuscle in-vivo afterTreatment with Surfactant Poloxamer 188.Biochim Biophys Acta.2007 May;1768(5):1238-1246.
[10] SANDRA B.CADICHON,HOANG M.LE,DAVID A.WRIGHT.Neuroprotective effect of the surfactant poloxamer 188 in amodel of intracranial hemorrhage in rats.Journal of Neurosurgeon,2007 (1 Suppl Pediatrics)106:36-40