Abstract
Amphipols (APols) are polymeric surfactants that keep membrane proteins (MPs) water-soluble in the absence of detergent, while stabilizing them. They can be used to deliver MPs and other hydrophobic molecules in vivo for therapeutic purposes, e.g., vaccination or targeted delivery of drugs. The biodistribution and elimination of the best characterized APol, a polyacrylate derivative called A8–35, have been examined in mice, using two fluorescent APols, grafted with either Alexa Fluor 647 or rhodamine. Three of the most common injection routes have been used, intravenous (IV), intraperitoneal (IP), and subcutaneous (SC). The biodistribution has been studied by in vivo fluorescence imaging and by determining the concentration of fluorophore in the main organs. Free rhodamine was used as a control. Upon IV injection, A8–35 distributes rapidly throughout the organism and is found in most organs but the brain and spleen, before being slowly eliminated (10–20 days). A similar pattern is observed after IP injection, following a brief latency period during which the polymer remains confined to the peritoneal cavity. Upon SC injection, A8–35 remains essentially confined to the point of injection, from which it is only slowly released. An interesting observation is that A8–35 tends to accumulate in fat pads, suggesting that it could be used to deliver anti-obesity drugs.
Similar content being viewed by others
References
Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O (2000) Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J Nutr 130:2943–2948
Charvolin D, Perez J-B, Rouvière F, Giusti F, Bazzacco P, Abdine A, Rappaport F, Martinez KL, Popot J-L (2009) The use of amphipols as universal molecular adapters to immobilize membrane proteins onto solid supports. Proc Natl Acad Sci USA 106:405–410
Destouches D, Page N, Hamma-Kourbali Y, Machi V, Chaloin O, Frechault S, Birmpas C, Katsoris P, Beyrath J, Albanese P, Maurer M, Carpentier G, Strub J-M, Van Dorsselaer A, Muller S, Bagnard D, Briand JP, Courty J (2011) A simple approach to cancer therapy afforded by multivalent pseudopeptides that target cell-surface nucleoproteins. Cancer Res 71:3296–3305
Ding H, Wu F (2012) Image guided biodistribution and pharmacokinetic studies of theranostics. Theranostics 2:1040–1053
Giusti F, Popot J-L, Tribet C (2012) Well-defined critical association concentration and rapid adsorption at the air/water interface of a short amphiphilic polymer, amphipol A8–35: a study by Förster resonance energy transfer and dynamic surface tension measurements. Langmuir 28:10372–10380
Gohon Y, Pavlov G, Timmins P, Tribet C, Popot J-L, Ebel C (2004) Partial specific volume and solvent interactions of amphipol A8–35. Anal Biochem 334:318–334
Gohon Y, Giusti F, Prata C, Charvolin D, Timmins P, Ebel C, Tribet C, Popot J-L (2006) Well-defined nanoparticles formed by hydrophobic assembly of a short and polydisperse random terpolymer, amphipol A8–35. Langmuir 22:1281–1290
Kim D, Park J-H, Kweon D-J, Han GD (2013) Bioavailability of nanoemulsified conjugated linoleic acid for an antiobesity effect. Int J Nanomed 8:451–459
Lai CP, Mardini O, Ericsson M, Prabhakar S, Maguire CA, Chen JW, Tannous BA, Breakefield XO (2014) Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano 8:483–594
Le Bon C, Popot J-L, Giusti F (2014) Labeling and functionalizing amphipols for biological applications. J Membr Biol. doi:10.1007/s00232-014-9655-y
Nasarre C, Roth M, Jacob L, Roth L, Koncina E, Thien A, Labourdette G, Poulet P, Hubert P, Crémel G, Roussel G, Aunis D, Bagnard D (2010) Peptide-based interference of the transmembrane domain of neuropilin-1 inhibits glioma growth in vivo. Oncogene 29:2381–2392
Page N, Gros F, Schall N, Décossas M, Bagnard D, Briand J-P, Muller S (2011) HSC70 blockade by the therapeutic peptide P140 affects autophagic processes and endogenous MHCII presentation in murine lupus. Ann Rheum Dis 70:837–843
Popot J-L, Berry EA, Charvolin D, Creuzenet C, Ebel C, Engelman DM, Flötenmeyer M, Giusti F, Gohon Y, Hervé P, Hong Q, Lakey JH, Leonard K, Shuman HA, Timmins P, Warschawski DE, Zito F, Zoonens M, Pucci B, Tribet C (2003) Amphipols: polymeric surfactants for membrane biology research. Cell Mol Life Sci 60:1559–1574
Popot J-L, Althoff T, Bagnard D, Banères J-L, Bazzacco P, Billon-Denis E, Catoire LJ, Champeil P, Charvolin D, Cocco MJ, Crémel G, Dahmane T, de la Maza LM, Ebel C, Gabel F, Giusti F, Gohon Y, Goormaghtigh E, Guittet E, Kleinschmidt JH, Kühlbrandt W, Le Bon C, Martinez KL, Picard M, Pucci B, Rappaport F, Sachs JN, Tribet C, van Heijenoort C, Wien F, Zito F, Zoonens M (2011) Amphipols from A to Z. Annu Rev Biophys 40:379–408
Schoellhammer CM, Blankschtein D, Langer R (2014) Skin permeabilization for transdermal drug delivery: recent advances and future prospects. Expert Opin Drug Deliv 11:393–407
Tifrea DF, Sun G, Pal S, Zardeneta G, Cocco MJ, Popot J-L, de la Maza LM (2011) Amphipols stabilize the Chlamydia major outer membrane protein and enhance its protective ability as a vaccine. Vaccine 29:4623–4631
Tifrea D, Pal S, Cocco MJ, Popot J-L, de la Maza LM (2014) Increased immuno accessibility of MOMP epitopes in a vaccine formulated with amphipols may account for the very robust protection elicited against a vaginal challenge with C. muridarum. J Immunol 192(11):5201–5213
Tribet C, Audebert R, Popot J-L (1996) Amphipols: polymers that keep membrane proteins soluble in aqueous solutions. Proc Natl Acad Sci USA 93:15047–15050
Tribet C, Audebert R, Popot J-L (1997) Stabilization of hydrophobic colloidal dispersions in water with amphiphilic polymers: application to integral membrane proteins. Langmuir 13:5570–5576
Tribet C, Diab C, Dahmane T, Zoonens M, Popot J-L, Winnik FM (2009) Thermodynamic characterization of the exchange of detergents and amphipols at the surfaces of integral membrane proteins. Langmuir 25:12623–12634
Zoonens M, Popot J-L (2014) Amphipols for each season. J Membrane Biol. doi:10.1007/s00232-014-9666-8
Zoonens M, Giusti F, Zito F, Popot J-L (2007) Dynamics of membrane protein/amphipol association studied by Förster resonance energy transfer. Implications for in vitro studies of amphipol-stabilized membrane proteins. Biochemistry 46:10392–10404
Acknowledgments
This work has been carried out within the LABEX ANR-10-LABX-0034 Medalis and received a financial support from French Government managed by “Agence National de la Recherche” under “Programme d’investissement d’avenir” and Fondation pour la Recherche Médicale (FRM/Rotary International), the French Centre National de la Recherche Scientifique, University Paris-7, U.S. National Grant R01AI092129 from the National Institute of Allergy and Infectious Diseases, French Agence Nationale pour la Recherche Grant “X-Or”, ANR SVSE5 2010-BLAN-1535, and Grant “DYNAMO”, ANR-11-LABX-0011-01 from the French “Initiative d’Excellence” Program.
Author information
Authors and Affiliations
Corresponding author
Additional information
Research article submitted for publication in the special issue of J. Membr. Biol. on amphipols and their applications.
Rights and permissions
About this article
Cite this article
Fernandez, A., Le Bon, C., Baumlin, N. et al. In Vivo Characterization of the Biodistribution Profile of Amphipol A8–35. J Membrane Biol 247, 1043–1051 (2014). https://doi.org/10.1007/s00232-014-9682-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00232-014-9682-8