Micellar Encapsulation of Propofol Reduces its Adsorption on Extracorporeal Membrane Oxygenator (ECMO) Circuit.
ECMO
adsorption
dosing
micelles
propofol
Journal
The AAPS journal
ISSN: 1550-7416
Titre abrégé: AAPS J
Pays: United States
ID NLM: 101223209
Informations de publication
Date de publication:
25 05 2023
25 05 2023
Historique:
received:
30
03
2023
accepted:
30
04
2023
medline:
26
5
2023
pubmed:
25
5
2023
entrez:
24
5
2023
Statut:
epublish
Résumé
Extracorporeal membrane oxygenation (ECMO) is a life-saving cardiopulmonary bypass device used on critically ill patients with refractory heart and lung failure. Patients supported with ECMO receive numerous drugs to treat critical illnesses and the underlying diseases. Unfortunately, most drugs prescribed to patients on ECMO lack accurate dosing information. Dosing can be variable in this patient population because the ECMO circuit components can adsorb drugs and affect drug exposure substantially. Propofol is a widely used anesthetic in ECMO patients and is known to have high adsorption rates in ECMO circuits due to its high hydrophobicity. In an attempt to reduce adsorption, we encapsulated propofol with Poloxamer 407 (Polyethylene-Polypropylene Glycol). Size and polydispersity index (PDI) were characterized using dynamic light scattering. Encapsulation efficiency was analyzed using High performance liquid chromatography. Cytocompatibility of micelles was analyzed against human macrophages and the formulation was finally injected in an ex-vivo ECMO circuit to determine the adsorption of propofol. Size and PDI of micellar propofol were 25.5 ± 0.8 nm and 0.08 ± 0.01, respectively. Encapsulation efficiency of the drug was 96.1 ± 1.3%. Micellar propofol demonstrated colloidal stability at physiological temperature for a period of 7 days, and was cytocompatible with human macrophages. Micellar propofol demonstrated a significant reduction in adsorption of propofol in the ECMO circuit at earlier time points compared to free propofol (Diprivan®). We observed 97 ± 2% recovery of the propofol from the micellar formulation after an infusion. These results demonstrate the potential of micellar propofol to reduce drug adsorption to ECMO circuit.
Identifiants
pubmed: 37225960
doi: 10.1208/s12248-023-00817-2
pii: 10.1208/s12248-023-00817-2
doi:
Substances chimiques
Propofol
YI7VU623SF
Micelles
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
52Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR002538
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.
Références
Buck ML. Pharmacokinetic changes during extracorporeal membrane oxygenation: implications for drug therapy of neonates. Clin Pharmacokinet. 2003;42:403–17.
doi: 10.2165/00003088-200342050-00001
pubmed: 12739981
Sherwin J, Heath T, Watt K. Pharmacokinetics and dosing of anti-infective drugs in patients on extracorporeal membrane oxygenation: a review of the current literature. Clin Ther. 2016;38:1976–94.
doi: 10.1016/j.clinthera.2016.07.169
pubmed: 27553752
pmcid: 5535730
Watt K, Li JS, Benjamin DK, Cohen-Wolkowiez M. Pediatric cardiovascular drug dosing in critically ill children and extracorporeal membrane oxygenation. J Cardiovasc Pharmacol. 2011;58:126–32.
doi: 10.1097/FJC.0b013e318213aac2
pubmed: 21346597
pmcid: 3155009
Palmgrén JJ, Mönkkönen J, Korjamo T, Hassinen A, Auriola S. Drug adsorption to plastic containers and retention of drugs in cultured cells under in vitro conditions. Eur J Pharm Biopharm. 2006;64:369–78.
doi: 10.1016/j.ejpb.2006.06.005
pubmed: 16905298
Preston TJ, Hodge AB, Riley JB, Leib-Sargel C, Nicol KK. In vitro drug adsorption and plasma free hemoglobin levels associated with hollow fiber oxygenators in the extracorporeal life support (ECLS) circuit. J Extra Corpor Technol. 2007;39:234–7.
pubmed: 18293808
pmcid: 4680688
Preston TJ, Ratliff TM, Gomez D, Olshove VE, Nicol KK, Sargel CL, Chicoine LG. Modified surface coatings and their effect on drug adsorption within the extracorporeal life support circuit. J Extra Corpor Technol. 2010;42:199–202.
pubmed: 21114222
pmcid: 4679959
Unger JK, Kuehlein G, Schroers A, Gerlach JC, Rossaint R. Adsorption of xenobiotics to plastic tubing incorporated into dynamic in vitro systems used in pharmacological research--limits and progress. Biomater. 2001;22:2031–7.
doi: 10.1016/S0142-9612(00)00389-6
Ahsman MJ, Hanekamp M, Wildschut ED, Tibboel D, Mathot RA. Population pharmacokinetics of midazolam and its metabolites during venoarterial extracorporeal membrane oxygenation in neonates. Clin Pharmacokinet. 2010;49:407–19.
doi: 10.2165/11319970-000000000-00000
pubmed: 20481651
Ahsman MJ, Wildschut ED, Tibboel D, Mathot RA. Pharmacokinetics of cefotaxime and desacetylcefotaxime in infants during extracorporeal membrane oxygenation. Antimicrob Agents Chemother. 2010;54:1734–41.
doi: 10.1128/AAC.01696-09
pubmed: 20176908
pmcid: 2863660
Harthan AA, Buckley KW, Heger ML, Fortuna RS, Mays K. Medication adsorption into contemporary extracorporeal membrane oxygenator circuits. J Pediatr Pharmacol Ther. 2014;19:288–95.
pubmed: 25762874
pmcid: 4341414
van der Vorst MM, Wildschut E, Houmes RJ, Gischler SJ, Kist-van Holthe JE, Burggraaf J, van der Heijden AJ, Tibboel D. Evaluation of furosemide regimens in neonates treated with extracorporeal membrane oxygenation. Crit Care. 2006;10:R168.
doi: 10.1186/cc5115
pubmed: 17140428
pmcid: 1794483
Wildschut ED, de Hoog M, Ahsman MJ, Tibboel D, Osterhaus AD, Fraaij PL. Plasma concentrations of oseltamivir and oseltamivir carboxylate in critically ill children on extracorporeal membrane oxygenation support. PLoS One. 2010;5:e10938.
doi: 10.1371/journal.pone.0010938
pubmed: 20532176
pmcid: 2880602
Mulla H, Lawson G, von Anrep C, Burke MD, Upton DU, Firmin RK, Killer H. In vitro evaluation of sedative drug losses during extracorporeal membrane oxygenation. Perfusion. 2000;15:21–6.
doi: 10.1177/026765910001500104
pubmed: 10676864
Mehta NM, Halwick DR, Dodson BL, Thompson JE, Arnold JH. Potential drug sequestration during extracorporeal membrane oxygenation: results from an ex vivo experiment. Intensive Care Med. 2007;33:1018–24.
doi: 10.1007/s00134-007-0606-2
pubmed: 17404709
Thompson KA, Goodale DB. The recent development of propofol (DIPRIVAN). Intensive Care Med. 2000;26(Suppl 4):S400–4.
doi: 10.1007/PL00003783
pubmed: 11310902
Servin F, Desmonts JM, Haberer JP, Cockshott ID, Plummer GF, Farinotti R. Pharmacokinetics and protein binding of propofol in patients with cirrhosis. Anesthesiol. 1988;69:887–91.
doi: 10.1097/00000542-198812000-00014
Lemaitre F, Hasni N, Leprince P, Corvol E, Belhabib G, Fillâtre P, Luyt CE, Leven C, Farinotti R, Fernandez C, Combes A. Propofol, midazolam, vancomycin and cyclosporine therapeutic drug monitoring in extracorporeal membrane oxygenation circuits primed with whole human blood. Crit Care. 2015;19:40.
doi: 10.1186/s13054-015-0772-5
pubmed: 25886890
pmcid: 4335544
Kabanov AV, Alakhov VY. Pluronic block copolymers in drug delivery: from micellar nanocontainers to biological response modifiers. Crit Rev Ther Drug Carrier Syst. 2002;19:1–72.
doi: 10.1615/CritRevTherDrugCarrierSyst.v19.i1.10
pubmed: 12046891
Kwon GS. Polymeric micelles for delivery of poorly water-soluble compounds. Crit Rev Ther Drug Carrier Syst. 2003;20:357–403.
doi: 10.1615/CritRevTherDrugCarrierSyst.v20.i5.20
pubmed: 14959789
Kabanov AV, Batrakova EV, Alakhov VY. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release. 2002;82:189–212.
doi: 10.1016/S0168-3659(02)00009-3
pubmed: 12175737
Imburgia CE, Rower JE, Green DJ, Mcknite AM, Kelley WE, Reilly CA, Watt KM. Remdesivir and GS-441524 extraction by ex vivo extracorporeal life support circuits. ASAIO J. 2022;68:1204–10.
doi: 10.1097/MAT.0000000000001616
pubmed: 34799526
Wright SP. Adjusted P-values for simultaneous inference. Biom. 1992;48:1005–13.
doi: 10.2307/2532694
Benjamini Y, Krieger AM, Yekutieli D. Adaptive linear step-up procedures that control the false discovery rate. Biometrika. 2006;93:491–507.
doi: 10.1093/biomet/93.3.491
He T, He J, Wang Z, Cui Z. Modification strategies to improve the membrane hemocompatibility in extracorporeal membrane oxygenator (ECMO). Adv Compos Hybrid Mater. 2021;4:847–64.
doi: 10.1007/s42114-021-00244-x
pubmed: 33969267
pmcid: 8091652
Kim SC, Kim DW, Shim YH, Bang JS, Oh HS, Wan Kim S, Seo MH. In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy. J Control Release. 2001;72:191–202.
doi: 10.1016/S0168-3659(01)00275-9
pubmed: 11389998
Cabral H, Miyata K, Osada K, Kataoka K. Block copolymer micelles in nanomedicine applications. Chem Rev. 2018;118:6844–92.
doi: 10.1021/acs.chemrev.8b00199
pubmed: 29957926
Daniel JM, Bernard PA, Skinner SC, Bhandary P, Ruzic A, Bacon MK, Ballard HO. Hollow Fiber oxygenator composition has a significant impact on failure rates in neonates on extracorporeal membrane oxygenation: a retrospective analysis. J Pediatr Intensive Care. 2018;7:7–13.
doi: 10.1055/s-0037-1599150
pubmed: 31073461
Lequier L, Horton SB, McMullan DM, Bartlett RH. Extracorporeal membrane oxygenation circuitry. Pediatr Crit Care Med. 2013;14:S7–12.
doi: 10.1097/PCC.0b013e318292dd10
pubmed: 23735989
pmcid: 3742331
Fragomeni G, Terzini M, Comite A, Catapano G. The maximal pore size of hydrophobic microporous membranes does not fully characterize the resistance to plasma breakthrough of membrane devices for extracorporeal blood oxygenation. Front Bioeng Biotechnol. 2019;7:461.
doi: 10.3389/fbioe.2019.00461
pubmed: 31998713
Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm Res. 2006;23:2709–28.
doi: 10.1007/s11095-006-9104-4
pubmed: 17096184
Fakhar-Ud-Din, Khan GM. Development and characterisation of levosulpiride-loaded suppositories with improved bioavailability in vivo. Pharm Dev Technol. 2019;24:63–9.
doi: 10.1080/10837450.2017.1419256
pubmed: 29251521
Alakhov V, Klinski E, Lemieux P, Pietrzynski G, Kabanov A. Block copolymeric biotransport carriers as versatile vehicles for drug delivery. Expert Opin Biol Ther. 2001;1:583–602.
doi: 10.1517/14712598.1.4.583
pubmed: 11727496