The Effect of Temperature on the Stability of PCSK-9 Monoclonal Antibody: An Experimental Study

Abstract Background: PCSK9 monoclonal antibody lowers plasma PCSK9 and LDL-cholesterol levels. The manufacturers recommend drug storage at 2–8°C, and not above 25°C. This study aimed to investigate drug stability at various temperatures that this drug could be exposed to during medication handling and transportation in tropical countries. Methods: Alirocumab and evolocumab were tested in 3 study conditions: room temperature (RT), cooler device with cold pack, and freeze-thaw for 9 and 18 hours. Heated drugs were used as negative control. Free plasma PCSK9 levels from 9 hyperlipidemia subjects were measured with ELISA. Results: Average subject age was 49.2±18.4 years. Percent PCSK9 inhibition significantly declined in heated drugs compared to baseline. Average RT during the study period was 30.4°C. Change in percent PCSK9 inhibition of PCSK9 mAb at RT from baseline was -5.8±4.4 (p=0.005) and -11.0±8.9% (p=0.006) for alirocumab at 9 hours and 18 hours, and -9.7±11.8% (p=0.04) and -15.1±14.3% (p=0.01) for evolocumab at 9 and 18 hours, respectively. In contrast, there were no significant changes in percent PCSK9 inhibition from baseline when PCSK9 mAb was stored in a cooler. In freeze-thaw condition, changes in percent PCSK9 inhibition from baseline to 9 and 18 hours were -5.2±2.9% (p=0.001) and -2.6±4.9% (p=0.16) for alirocumab, and -1.8±4.2% (p=0.24) and 0.4±6.1% (p=0.83) for evolocumab. Conclusion: Proper drug storage according to manufacturer’s recommendation is essential. Drug storage at RT in tropical climate for longer than 9 hours significantly decreased drug efficacy; however, storage in a cooler device with cold pack for up to 18 hours is safe.

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The effect of temperature on the stability of PCSK-9 monoclonal antibody: an experimental study

Lipids in Health and Disease ◽

10.1186/s12944-021-01447-3 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Tanawan Kongmalai ◽

Nalinee Chuanchaiyakul ◽

Chattip Sripatumtong ◽

Tunsuda Tansit ◽

Yuttana Srinoulprasert ◽

...

Keyword(s):

Monoclonal Antibody ◽

Drug Stability ◽

Drug Efficacy ◽

Negative Control ◽

Effect Of Temperature ◽

Freeze Thaw ◽

Drug Storage ◽

Pcsk9 Inhibition ◽

The Stability ◽

Cold Pack

Abstract Background PCSK9 monoclonal antibody lowers plasma PCSK9 and LDL-cholesterol levels. The manufacturers recommend drug storage at 2–8 °C, and not above 25 °C. This study aimed to investigate drug stability at various temperatures that this drug could be exposed to during medication handling and transportation in tropical countries. Methods Alirocumab and evolocumab were tested in 3 study conditions: room temperature (RT), cooler device with cold pack, and freeze-thaw for 9 and 18 h. Heated drugs were used as negative control. Free plasma PCSK9 levels from 9 hyperlipidemia subjects were measured with ELISA. Results Average subject age was 49.2 ± 18.4 years. Percent PCSK9 inhibition significantly declined in heated drugs compared to baseline. Average RT during the study period was 30.4 ±2.6 °C. Change in percent PCSK9 inhibition of PCSK9 mAb at RT from baseline was − 5.8 ± 4.4% (P = 0.005) and − 11.0 ± 8.9% (P = 0.006) for alirocumab at 9 h and 18 h, and − 9.7 ± 11.8% (P = 0.04) and − 15.1 ± 14.3% (P = 0.01) for evolocumab at 9 and 18 h, respectively. In contrast, there were no significant changes in percent PCSK9 inhibition from baseline when PCSK9 mAb was stored in a cooler. In freeze-thaw condition, changes in percent PCSK9 inhibition from baseline to 9 and 18 h were − 5.2 ± 2.9% (P = 0.001) and − 2.6 ± 4.9% (P = 0.16) for alirocumab, and − 1.8 ± 4.2% (P = 0.24) and 0.4 ± 6.1% (P = 0.83) for evolocumab. Conclusion Proper drug storage according to manufacturer’s recommendation is essential. Drug storage at RT in tropical climate for longer than 9 h significantly decreased drug efficacy; however, storage in a cooler device with cold pack for up to 18 h is safe.

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Su1216 Effect of Temperature, Time and Freeze/Thaw Cycles on the Stability of Fecal Hemoglobin Using Five Commercial Fecal Immunochemical Test (FIT) Methods and One Guaiac Method

Gastroenterology ◽

10.1016/s0016-5085(14)61462-1 ◽

2014 ◽

Vol 146 (5) ◽

pp. S-404 ◽

Cited By ~ 4

Author(s):

Peter Catomeris ◽

Nancy N. Baxter ◽

Sheila Boss ◽

Lawrence Paszat ◽

Linda Rabeneck ◽

...

Keyword(s):

Fecal Immunochemical Test ◽

Effect Of Temperature ◽

Freeze Thaw ◽

Immunochemical Test ◽

The Stability ◽

Temperature Time

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Applicability of Instability Index for In vitro Protein Stability Prediction

Protein and Peptide Letters ◽

10.2174/0929866526666190228144219 ◽

2019 ◽

Vol 26 (5) ◽

pp. 339-347 ◽

Cited By ~ 4

Author(s):

Dilani G. Gamage ◽

Ajith Gunaratne ◽

Gopal R. Periyannan ◽

Timothy G. Russell

Keyword(s):

Protein Stability ◽

Caulobacter Crescentus ◽

Effect Of Temperature ◽

Instability Index ◽

Dipeptide Composition ◽

Experimental Conditions ◽

The Stability ◽

Vitro Protein

Background: The dipeptide composition-based Instability Index (II) is one of the protein primary structure-dependent methods available for in vivo protein stability predictions. As per this method, proteins with II value below 40 are stable proteins. Intracellular protein stability principles guided the original development of the II method. However, the use of the II method for in vitro protein stability predictions raises questions about the validity of applying the II method under experimental conditions that are different from the in vivo setting. Objective: The aim of this study is to experimentally test the validity of the use of II as an in vitro protein stability predictor. Methods: A representative protein CCM (CCM - Caulobacter crescentus metalloprotein) that rapidly degrades under in vitro conditions was used to probe the dipeptide sequence-dependent degradation properties of CCM by generating CCM mutants to represent stable and unstable II values. A comparative degradation analysis was carried out under in vitro conditions using wildtype CCM, CCM mutants and two other candidate proteins: metallo-β-lactamase L1 and α -S1- casein representing stable, borderline stable/unstable, and unstable proteins as per the II predictions. The effect of temperature and a protein stabilizing agent on CCM degradation was also tested. Results: Data support the dipeptide composition-dependent protein stability/instability in wt-CCM and mutants as predicted by the II method under in vitro conditions. However, the II failed to accurately represent the stability of other tested proteins. Data indicate the influence of protein environmental factors on the autoproteolysis of proteins. Conclusion: Broader application of the II method for the prediction of protein stability under in vitro conditions is questionable as the stability of the protein may be dependent not only on the intrinsic nature of the protein but also on the conditions of the protein milieu.

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Evaluation of the effect of temperature on the stability and antimicrobial activity of rifampicin quinone

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2021.113941 ◽

2021 ◽

Vol 197 ◽

pp. 113941

Author(s):

Indorica Sutradhar ◽

Muhammad H. Zaman

Keyword(s):

Antimicrobial Activity ◽

Effect Of Temperature ◽

The Stability

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The effect of temperature and time on the properties of 2D Cs2ZnBr4 perovskite nanocrystals and its application in a Schottky barrier device

Journal of Materials Chemistry C ◽

10.1039/d1tc00264c ◽

2021 ◽

Author(s):

Olusola Akinbami ◽

Grace N Ngubeni ◽

Francis Otieno ◽

Rudo Kadzutu-Sithole ◽

Cebisa Linganiso ◽

...

Keyword(s):

Solar Cell ◽

Schottky Barrier ◽

Effect Of Temperature ◽

Inorganic Perovskite ◽

Perovskite Nanocrystals ◽

The Stability ◽

Barrier Device

2D hybrid perovskites are promising materials for solar cell applications, in particular, cesium based perovskite nanocrystals as they offer the stability that is absent in organic-inorganic perovskite. However, the most...

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Temperature Dependence of Degradation of Colored Oxo-Biodegradable Low-Density Polyethylene Films under Accelerated Thermal Aging

Materials Science Forum ◽

10.4028/www.scientific.net/msf.890.82 ◽

2017 ◽

Vol 890 ◽

pp. 82-85 ◽

Cited By ~ 1

Author(s):

Reymark D. Maalihan ◽

Bryan B. Pajarito

Keyword(s):

Thermal Aging ◽

Degradation Products ◽

Low Density Polyethylene ◽

Effect Of Temperature ◽

Low Density ◽

Polyethylene Films ◽

Hot Air ◽

Taguchi Design Of Experiments ◽

Oxidant Concentration ◽

The Stability

This work reports the effect of temperature on degradation of colored low-density polyethylene (PE) films during thermal aging. Film samples were formulated according to Taguchi design of experiments where colorant, thickness, and pro-oxidant concentration were varied accordingly. Tensile properties of films were monitored with time during heat aging in a hot air oven at 50, 70, and 90 °C. Likewise, surfaces of aged films were analyzed to evaluate the degree of oxidation of PE during thermal aging. The Arrhenius equation was then used to predict the lifetime of PE at an in-use temperature of 30 °C. Results indicate that increasing the temperature reduces the tensile strength and modulus of films. Formation of carbonyl groups as degradation products is also observed at higher temperatures. Consequently, thermal aging at 90 °C offers the highest extent of degradation of exposed films. Regression analysis reveals that white films degrade at a higher rate than yellow and non-colored films. The presence of TiO2 in white films shortens the lifetime of PE while amine stabilizer in yellow films enhances the stability of PE during thermal aging.

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Durability of BFRP and Hybrid FRP Sheets under Freeze-Thaw Cycling

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.163-167.3297 ◽

2010 ◽

Vol 163-167 ◽

pp. 3297-3300 ◽

Cited By ~ 9

Author(s):

Jia Wei Shi ◽

Hong Zhu ◽

Zhi Shen Wu ◽

Gang Wu

Keyword(s):

Mechanical Properties ◽

Test Data ◽

Mechanical Characteristics ◽

Test Results ◽

Freeze Thaw ◽

Frp Composites ◽

Test Parameters ◽

The Stability ◽

Better Than

Coupon tests were conducted to investigate the mechanical characteristics of basalt FRP (BFRP) sheet, basalt-carbon hybrid FRP sheets and the corresponding epoxy rein under the effect of freeze-thaw cycling. FRP sheets and epoxy rein coupons were subjected to up to 200 and 250 freeze-thaw cycles respectively. Test parameters included the number of freeze-thaw cycles and the types of FRP composites. Test results show that (1) BFRP sheet perform better than CFRP or GFRP sheets under high freeze-thaw cycles; (2) exposed hybrid FRP sheets not only show very little loss in mechanical properties, but also contribute to the stability of test data; (3) mechanical properties of rein epoxy decrease significantly with increasing freeze-thaw cycles.

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Higher Performance of DSSC with Dyes from Cladophora sp. as Mixed Cosensitizer through Synergistic Effect

Journal of Biophysics ◽

10.1155/2015/510467 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 27

Author(s):

Andery Lim ◽

Noramaliyana Haji Manaf ◽

Kushan Tennakoon ◽

R. L. N. Chandrakanthi ◽

Linda Biaw Leng Lim ◽

...

Keyword(s):

Synergistic Effect ◽

Structural Changes ◽

Dye Sensitized Solar Cells ◽

Life Time ◽

Effect Of Temperature ◽

Synergistic Activity ◽

Electron Recombination ◽

Positive Interaction ◽

Effective Electron ◽

The Stability

Chlorophyll and xanthophyll dyes extracted from a single source of filamentous freshwater green algae (Cladophora sp.) were used to sensitize dye sensitized solar cells and their performances were investigated. A more positive interaction is expected as the derived dyes come from a single natural source because they work mutually in nature. Cell sensitized with mixed chlorophyll and xanthophyll showed synergistic activity with improved cell performance of 1.5- to 2-fold higher than that sensitized with any individual dye. The effect of temperature and the stability of these dyes were also investigated. Xanthophyll dye was found to be more stable compared to chlorophyll that is attributed in the ability of xanthophyll to dissipate extra energy via reversible structural changes. Mixing the dyes resulted to an increase in effective electron life time and reduced the process of electron recombination during solar cell operation, hence exhibiting a synergistic effect.

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