Poloxamer 188 as surfactant in biological formulations – An alternative for polysorbate 20/80?

Bollenbach, Lukas; Buske, Julia; Mäder, Karsten; Garidel, Patrick

doi:10.1016/j.ijpharm.2022.121706

Cited by 61 publications

(40 citation statements)

References 171 publications

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“…Its T m was found to be approximately 56 • C according to both techniques, while the enthalpy associated to the transition was around 0.04 J/g of solution. The observed T m value for Poloxamer 188 water dispersion was in accordance with the literature: indeed, a single endothermic transition can be recognized, probably related to dehydration of the PEO-rich corona, leading to the formation of micelles or the transformation of micelles into other aggregates [30][31][32]. All hybrid samples showed an endothermic transition in the range 45-55 • C related to the Poloxamer 188 thermal transition, which is affected by the addition of the different non-ionic surfactant according to various weight ratios.…”

Section: Thermal Characterization By Microdscsupporting

confidence: 90%

“…Such phenomena related to poor solubility are to be further examined via the thermal characterization of the nanosystems, where the temperature increase during microDSC characterization can be used for the cmc evaluation [29]. It is important to note that the cmc values of Poloxamer 188 reported from various publications are quite diverse, a phenomenon that might be attributed to the method used for cmc determination (surface tension vs. solubilization/dye methods), as well as to possible differences regarding the purity/grade of the triblock copolymer used [30].…”

Section: Fluorescence Spectroscopy Resultsmentioning

confidence: 99%

“…Therefore, the T m decreased after the introduction of the surfactant molecules to Poloxamer 188 solutions in all prepared samples. recognized, probably related to dehydration of the PEO-rich corona, leading to the formation of micelles or the transformation of micelles into other aggregates [30][31][32]. All hybrid samples showed an endothermic transition in the range 45-55 °C related to the Poloxamer 188 thermal transition, which is affected by the addition of the different nonionic surfactant according to various weight ratios.…”

Section: Thermal Characterization By Microdscmentioning

confidence: 98%

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Non-Ionic Surfactant Effects on Innate Pluronic 188 Behavior: Interactions, and Physicochemical and Biocompatibility Studies

Kontogiannis

Selianitis

Perinelli

et al. 2022

IJMS

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The aim of this research was to prepare novel block copolymer-surfactant hybrid nanosystems using the triblock copolymer Pluronic 188, along with surfactants of different hydrophilic to lipophilic balance (HLB ratio—which indicates the degree to which a surfactant is hydrophilic or hydrophobic) and thermotropic behavior. The surfactants used were of non-ionic nature, of which Tween 80® and Brij 58® were more hydrophilic, while Span 40® and Span 60® were more hydrophobic. Each surfactant has unique innate thermal properties and an affinity towards Pluronic 188. The nanosystems were formulated through mixing the pluronic with the surfactants at three different ratios, namely 90:10, 80:20, and 50:50, using the thin-film hydration technique and keeping the pluronic concentration constant. The physicochemical characteristics of the prepared nanosystems were evaluated using various light scattering techniques, while their thermotropic behavior was characterized via microDSC and high-resolution ultrasound spectroscopy. Microenvironmental parameters were attained through the use of fluorescence spectroscopy, while the cytotoxicity of the nanocarriers was studied in vitro. The results indicate that the combination of Pluronic 188 with the above surfactants was able to produce hybrid homogeneous nanoparticle populations of adequately small diameters. The different surfactants had a clear effect on physicochemical parameters such as the size, hydrodynamic diameter, and polydispersity index of the final formulation. The mixing of surfactants with the pluronic clearly changed its thermotropic behavior and thermal transition temperature (Tm) and highlighted the specific interactions that occurred between the different materials, as well as the effect of increasing the surfactant concentration on inherent polymer characteristics and behavior. The formulated nanosystems were found to be mostly of minimal toxicity. The obtained results demonstrate that the thin-film hydration method can be used for the formulation of pluronic-surfactant hybrid nanoparticles, which in turn exhibit favorable characteristics in terms of their possible use in drug delivery applications. This investigation can be used as a road map for the selection of an appropriate nanosystem as a novel vehicle for drug delivery.

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Section: Thermal Characterization By Microdscsupporting

confidence: 90%

Section: Fluorescence Spectroscopy Resultsmentioning

confidence: 99%

Section: Thermal Characterization By Microdscmentioning

confidence: 98%

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Non-Ionic Surfactant Effects on Innate Pluronic 188 Behavior: Interactions, and Physicochemical and Biocompatibility Studies

Kontogiannis

Selianitis

Perinelli

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Surfactants are thought to protect proteins against interfacial damage by competing with proteins for adsorption sites on different interfaces, such as air–water, solid–water, and oil–water interfaces [ 4 , 5 ]. Owing to their decades of parenteral use in humans and demonstrated safety [ 6 ], polysorbate 80 (PS 80) and polysorbate 20 (PS 20) are considered the choice surfactants used in more than 90% of approved mAbs products [ 7 ]. However, in recent years, there have been increasing concerns about polysorbate degradation and its impact on the safety and quality of these biotherapeutic products.…”

Section: Introductionmentioning

confidence: 99%

Polysorbates versus Hydroxypropyl Beta-Cyclodextrin (HPβCD): Comparative Study on Excipient Stability and Stabilization Benefits on Monoclonal Antibodies

Zhang¹,

Hong²,

Tan³

et al. 2022

Molecules

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Polysorbates (PS 20 and PS 80) are the most widely used surfactants in biopharmaceutical formulations to protect proteins from denaturation, aggregation, and surface adsorption. To date, around 70% of marketed therapeutic antibodies contain either PS 20 or PS 80 in their formulations. However, polysorbates are chemically diverse mixtures, which are prone to degradation by oxidation and hydrolysis to produce peroxides and fatty acids, which, in turn, induce protein oxidation, aggregation, and insoluble particle formation. These will negatively impact protein quality and stability. Thus, polysorbate degradation has emerged as one of the major challenges in the development and commercialization of therapeutic protein products. KLEPTOSE® HPβCD (hydroxypropyl beta-cyclodextrin), a new multifunctional excipient, has been shown to provide protein stabilization functions in biopharmaceutical downstream processes and in their final formulations. This study aims to evaluate HPβCD, a new molecule of its class, against polysorbates as a stabilizer in biologics formulations. In this study, the chemical stability of KLEPTOSE® HPβCDs is compared with polysorbates (20 and 80) under various stress conditions. When subjected to heat stress, HPβCDs show little change in product recovery (90.7–100.7% recovery for different HPβCDs), while polysorbates 20 and 80 show significant degradation, with only 11.5% and 7.3% undegraded product remaining, respectively. When subjected to other chemical stressors, namely, autoclave, light, and oxidative stresses, HPβCD remains almost stable, while polysorbates show more severe degradation, with 95.5% to 98.8% remaining for polysorbate 20 and 85.5% to 97.4% remaining for polysorbate 80. Further, profiling characterization and degradation analysis reveal that chemical structures of HPβCDs remain intact, while polysorbates undergo significant hydrolytic degradation and oxidation. Lastly, the physicochemical stability of monoclonal antibodies in formulations is investigated. When subjected to light stress, adalimumab, as a model mAb, formulated in the presence of HPβCD, shows a significant decrease in protein aggregation, and superior monomer and total protein recovery compared to PS 80-containing formulations. HPβCD also reduces both agitation and thermal stress-induced protein aggregation and prevents subvisible particle formation compared to PS 80.

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“…It can improve the oral availability of hydrophobic drugs [ 13 ] and stabilize liquid formulations containing biologicals such as antibodies and proteins, although the exact mechanism of the observed stabilizing activity remains unknown [ 14 ]. Recently, several antibody formulations containing F68 were approved for clinical application [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Non-Viral Vectors Based on Pluronic® F68PEI with Application in Oncology Field

et al. 2022

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Copolymers composed of low-molecular-weight polyethylenimine (PEI) and amphiphilic Pluronics® are safe and efficient non-viral vectors for pDNA transfection. A variety of Pluronic® properties provides a base for tailoring transfection efficacy in combination with the unique biological activity of this polymer group. In this study, we describe the preparation of new copolymers based on hydrophilic Pluronic® F68 and PEI (F68PEI). F68PEI polyplexes obtained by doping with free F68 (1:2 and 1:5 w/w) allowed for fine-tuning of physicochemical properties and transfection activity, demonstrating improved in vitro transfection of the human bone osteosarcoma epithelial (U2OS) and oral squamous cell carcinoma (SCC-9) cells when compared to the parent formulation, F68PEI. Although all tested systems condensed pDNA at varying polymer/DNA charge ratios (N/P, 5/1–100/1), the addition of free F68 (1:5 w/w) resulted in the formation of smaller polyplexes (<200 nm). Analysis of polyplex properties by transmission electron microscopy and dynamic light scattering revealed varied polyplex morphology. Transfection potential was also found to be cell-dependent and significantly higher in SCC-9 cells compared to the control bPEI25k cells, as especially evident at higher N/P ratios (>25). The observed selectivity towards transfection of SSC-9 cells might represent a base for further optimization of a cell-specific transfection vehicle.

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Poloxamer 188 as surfactant in biological formulations – An alternative for polysorbate 20/80?

Cited by 61 publications

References 171 publications

Non-Ionic Surfactant Effects on Innate Pluronic 188 Behavior: Interactions, and Physicochemical and Biocompatibility Studies

Non-Ionic Surfactant Effects on Innate Pluronic 188 Behavior: Interactions, and Physicochemical and Biocompatibility Studies

Polysorbates versus Hydroxypropyl Beta-Cyclodextrin (HPβCD): Comparative Study on Excipient Stability and Stabilization Benefits on Monoclonal Antibodies

Novel Non-Viral Vectors Based on Pluronic® F68PEI with Application in Oncology Field

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