[en] Surface modification of lipid nanocapsules (LNC) is necessary to impart stealth properties to these drug carriers and enhance their accumulation into the tumor microenvironment. While pegylation is commonly used to prolong the circulation time of LNC, the increased presence of anti-PEG antibodies in the human population and the internalization issues associated to the PEG shell are strong incentives to search alternatives. This work describes the development of amphiphilic poly(N-vinyl amide)-based (co)polymers, including pH-responsive ones, and their use as LNC modifiers towards improved drug delivery systems. RAFT polymerization gave access to a series of LNC modifiers composed of poly(N-methyl-N-vinyl acetamide), poly(N-vinyl pyrrolidone) or pH-responsive vinylimidazole-based sequence bearing a variety of lipophilic end-groups, namely octadecyl, dioctadecyl or phospholipid groups, for anchoring to the LNC. Decoration of the LNC with these families of poly(N-vinyl amide) derivatives was achieved via both post-insertion and per-formulation methods. This offered valuable and non-toxic LNC protection from opsonization by complement activation, emphasized the benefit of dioctadecyl in the per-formulation approach and highlighted the great potential of poly(N-methyl-N-vinyl acetamide) as PEG alternative. Moreover, incorporation of imidazole moieties in the shell of the carrier imparted pH-responsiveness to the LNC likely to increase the cellular uptake in the acidic tumor microenvironment, opening up new possibilities in the field of active targeting.
Research center :
CERM - Center for Education and Research on Macromolecules - ULiège [BE] CESAM - Complex and Entangled Systems from Atoms to Materials - ULiège [BE]
Toussaint, François ; University of Liège [ULiège] - Complex and Entangled Systems from Atoms to Materials [CESAM] Research Unit - Center for Education and Research on Macromolecules [CERM] - Belgium
Lepeltier, Elise; University of Angers - INSERM - Micro et Nanomedecines Translationnelles [MINT] - France ; IUF - Institut Universitaire de France [IUF] - France
Franconi, Florence; University of Angers - INSERM - Micro et Nanomedecines Translationnelles [MINT] - France
Pautu, Vincent ; University of Angers - INSERM - Micro et Nanomedecines Translationnelles [MINT] - France
Jérôme, Christine ; University of Liège [ULiège] - Complex and Entangled Systems from Atoms to Materials [CESAM] Research Unit - Center for Education and Research on Macromolecules [CERM] - Belgium
Passirani, Catherine; University of Angers - INSERM - Micro et Nanomedecines Translationnelles [MINT] - France
Debuigne, Antoine ; University of Liège [ULiège] - Complex and Entangled Systems from Atoms to Materials [CESAM] Research Unit - Center for Education and Research on Macromolecules [CERM] - Belgium
Language :
English
Title :
Diversely substituted poly(N-vinyl amide) derivatives towards non-toxic, stealth and pH-responsive lipid nanocapsules.
Publication date :
March 2024
Journal title :
Colloids and Surfaces B: Biointerfaces
ISSN :
0927-7765
Publisher :
Elsevier B.V., Netherlands
Volume :
235
Pages :
113788
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
The "LIPEGALT" project
Funders :
F.R.S.-FNRS - Fund for Scientific Research [BE] FWB - Fédération Wallonie-Bruxelles [BE] ULiège. - ARC - Université de Liège. Actions de Recherche Concertées [BE]
Funding text :
The research was supported by the Wallonia-Brussels Federation (grant for Concerted Research Actions, LIPEGALT project, ULiège), carried out in collaboration with Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, ULiege (Prof. G. Piel) and the Gene Expression and Cancer Laboratory (GEC) , GIGA-Molecular Biology of Diseases , ULiege (Dr. D. Mottet). A.D. is FNRS Senior Research Associate and thanks the F.R.S.-FNRS for financial support.
Wang, S., Huang, P., Chen, X., Stimuli-responsive programmed specific targeting in nanomedicine. ACS Nano 10 (2016), 2991–2994, 10.1021/acsnano.6b00870.
Narum, S.M., Le, T., Le, D.P., Lee, J.C., Donahue, N.D., Yang, W., Wilhelm, S., Passive targeting in nanomedicine: fundamental concepts, body interactions, and clinical potential. Nanoparticles Biomed. Appl, 2020, Elsevier, 37–53, 10.1016/B978-0-12-816662-8.00004-7.
Bami, M.S., Raeisi Estabragh, M.A., Khazaeli, P., Ohadi, M., Dehghannoudeh, G., pH-responsive drug delivery systems as intelligent carriers for targeted drug therapy: brief history, properties, synthesis, mechanism and application. J. Drug Deliv. Sci. Technol., 70, 2022, 102987, 10.1016/j.jddst.2021.102987.
Huynh, N.T., Passirani, C., Saulnier, P., Benoit, J.P., Lipid nanocapsules: a new platform for nanomedicine. Int. J. Pharm. 379 (2009), 201–209, 10.1016/j.ijpharm.2009.04.026.
Heurtault, B., Saulnier, P., Pech, B., Proust, J.E., Benoit, J.P., A novel phase inversion-based process for the preparation of lipid nanocarriers. Pharm. Res. 19 (2002), 875–880, 10.1023/A:1016121319668.
Garcion, E., Lamprecht, A., Heurtault, B., Paillard, A., Aubert-Pouessel, A., Denizot, B., Menei, P., Benoît, J.-P., A new generation of anticancer, drug-loaded, colloidal vectors reverses multidrug resistance in glioma and reduces tumor progression in rats. Mol. Cancer Ther. 5 (2006), 1710–1722, 10.1158/1535-7163.MCT-06-0289.
Lamprecht, A., Benoit, J.-P., Etoposide nanocarriers suppress glioma cell growth by intracellular drug delivery and simultaneous P-glycoprotein inhibition. J. Control. Release 112 (2006), 208–213, 10.1016/j.jconrel.2006.02.014.
Fathy Abd-Ellatef, G.-E., Gazzano, E., Chirio, D., Ragab Hamed, A., Belisario, D.C., Zuddas, C., Peira, E., Rolando, B., Kopecka, J., Assem Said Marie, M., Sapino, S., Ramadan Fahmy, S., Gallarate, M., Zaki Abdel-Hamid, A.-H., Riganti, C., Curcumin-loaded solid lipid nanoparticles bypass P-glycoprotein mediated doxorubicin resistance in triple negative breast cancer cells. Pharmaceutics, 12, 2020, 96, 10.3390/pharmaceutics12020096.
Allard, E., Passirani, C., Garcion, E., Pigeon, P., Vessières, A., Jaouen, G., Benoit, J.-P., Lipid nanocapsules loaded with an organometallic tamoxifen derivative as a novel drug-carrier system for experimental malignant gliomas. J. Control. Release 130 (2008), 146–153, 10.1016/j.jconrel.2008.05.027.
Allard, E., Huynh, N.T., Vessières, A., Pigeon, P., Jaouen, G., Benoit, J.-P., Passirani, C., Dose effect activity of ferrocifen-loaded lipid nanocapsules on a 9L-glioma model. Int. J. Pharm. 379 (2009), 317–323, 10.1016/j.ijpharm.2009.05.031.
Allard, E., Jarnet, D., Vessières, A., Vinchon-Petit, S., Jaouen, G., Benoit, J.-P., Passirani, C., Local delivery of ferrociphenol lipid nanocapsules followed by external radiotherapy as a synergistic treatment against intracranial 9L glioma xenograft. Pharm. Res. 27 (2010), 56–64, 10.1007/s11095-009-0006-0.
Huynh, N.T., Morille, M., Bejaud, J., Legras, P., Vessieres, A., Jaouen, G., Benoit, J.-P., Passirani, C., Treatment of 9L gliosarcoma in rats by ferrociphenol-loaded lipid nanocapsules based on a passive targeting strategy via the EPR effect. Pharm. Res. 28 (2011), 3189–3198, 10.1007/s11095-011-0501-y.
Laine, A.-L., Huynh, N.T., Clavreul, A., Balzeau, J., Béjaud, J., Vessieres, A., Benoit, J.-P., Eyer, J., Passirani, C., Brain tumour targeting strategies via coated ferrociphenol lipid nanocapsules. Eur. J. Pharm. Biopharm. 81 (2012), 690–693, 10.1016/j.ejpb.2012.04.012.
Huynh, N.T., Passirani, C., Allard-Vannier, E., Lemaire, L., Roux, J., Garcion, E., Vessieres, A., Benoit, J.-P., Administration-dependent efficacy of ferrociphenol lipid nanocapsules for the treatment of intracranial 9L rat gliosarcoma. Int. J. Pharm. 423 (2012), 55–62, 10.1016/j.ijpharm.2011.04.037.
Lainé, A.-L., Adriaenssens, E., Vessières, A., Jaouen, G., Corbet, C., Desruelles, E., Pigeon, P., Toillon, R.-A., Passirani, C., The in vivo performance of ferrocenyl tamoxifen lipid nanocapsules in xenografted triple negative breast cancer. Biomaterials 34 (2013), 6949–6956, 10.1016/j.biomaterials.2013.05.065.
Lainé, A.-L., Clavreul, A., Rousseau, A., Tétaud, C., Vessieres, A., Garcion, E., Jaouen, G., Aubert, L., Guilbert, M., Benoit, J.-P., Toillon, R.-A., Passirani, C., Inhibition of ectopic glioma tumor growth by a potent ferrocenyl drug loaded into stealth lipid nanocapsules. Nanomed. Nanotechnol. Biol. Med. 10 (2014), 1667–1677, 10.1016/j.nano.2014.05.002.
Topin-Ruiz, S., Mellinger, A., Lepeltier, E., Bourreau, C., Fouillet, J., Riou, J., Jaouen, G., Martin, L., Passirani, C., Clere, N., p722 ferrocifen loaded lipid nanocapsules improve survival of murine xenografted-melanoma via a potentiation of apoptosis and an activation of CD8+ T lymphocytes. Int. J. Pharm., 593, 2021, 120111, 10.1016/j.ijpharm.2020.120111.
Perrier, T., Saulnier, P., Fouchet, F., Lautram, N., Benoît, J.-P., Post-insertion into Lipid NanoCapsules (LNCs): From experimental aspects to mechanisms. Int. J. Pharm. 396 (2010), 204–209, 10.1016/j.ijpharm.2010.06.019.
Lainé, A.-L., Gravier, J., Henry, M., Sancey, L., Béjaud, J., Pancani, E., Wiber, M., Texier, I., Coll, J.-L., Benoit, J.-P., Passirani, C., Conventional versus stealth lipid nanoparticles: formulation and in vivo fate prediction through FRET monitoring. J. Control. Release 188 (2014), 1–8, 10.1016/j.jconrel.2014.05.042.
Heurtault, B., Saulnier, P., Pech, B., Proust, J., Benoı̂t, J., Properties of polyethylene glycol 660 12-hydroxy stearate at a triglyceride/water interface. Int. J. Pharm. 242 (2002), 167–170, 10.1016/S0378-5173(02)00144-8.
Kozma, G.T., Shimizu, T., Ishida, T., Szebeni, J., Anti-PEG antibodies: properties, formation, testing and role in adverse immune reactions to PEGylated nano-biopharmaceuticals. Adv. Drug Deliv. Rev. 154–155 (2020), 163–175, 10.1016/j.addr.2020.07.024.
Zalba, S., ten Hagen, T.L.M., Burgui, C., Garrido, M.J., Stealth nanoparticles in oncology: facing the PEG dilemma. J. Control. Release 351 (2022), 22–36, 10.1016/j.jconrel.2022.09.002.
Ibrahim, M., Ramadan, E., Elsadek, N.E., Emam, S.E., Shimizu, T., Ando, H., Ishima, Y., Elgarhy, O.H., Sarhan, H.A., Hussein, A.K., Ishida, T., Polyethylene glycol (PEG): the nature, immunogenicity, and role in the hypersensitivity of PEGylated products. J. Control. Release 351 (2022), 215–230, 10.1016/j.jconrel.2022.09.031.
Hirsjärvi, S., Dufort, S., Bastiat, G., Saulnier, P., Passirani, C., Coll, J.L., Benoît, J.P., Surface modification of lipid nanocapsules with polysaccharides: from physicochemical characteristics to in vivo aspects. Acta Biomater. 9 (2013), 6686–6693, 10.1016/j.actbio.2013.01.038.
Béduneau, A., Saulnier, P., Hindré, F., Clavreul, A., Leroux, J.-C., Benoit, J.-P., Design of targeted lipid nanocapsules by conjugation of whole antibodies and antibody Fab’ fragments. Biomaterials 28 (2007), 4978–4990, 10.1016/j.biomaterials.2007.05.014.
Karim, R., Lepeltier, E., Esnault, L., Pigeon, P., Lemaire, L., Lépinoux-Chambaud, C., Clere, N., Jaouen, G., Eyer, J., Piel, G., Passirani, C., Enhanced and preferential internalization of lipid nanocapsules into human glioblastoma cells: effect of a surface-functionalizing NFL peptide. Nanoscale 10 (2018), 13485–13501, 10.1039/C8NR02132E.
Pautu, V., Lepeltier, E., Mellinger, A., Riou, J., Debuigne, A., Jerome, C., Clere, N., Passirani, C., pH-Responsive lipid nanocapsules: a promising strategy for improved resistant melanoma cell internalization. Cancers, 13, 2021, 2028 https://doi.org/10.3390/cancers13092028 CO - CANCCT.
Berger, M., Toussaint, F., Djemaa, S.Ben, Laloy, J., Pendeville, H., Evrard, B., Jerôme, C., Lechanteur, A., Mottet, D., Debuigne, A., Piel, G., Poly(vinyl pyrrolidone) derivatives as PEG alternatives for stealth, non-toxic and less immunogenic siRNA-containing lipoplex delivery. J. Control. Release 361 (2023), 87–101, 10.1016/j.jconrel.2023.07.031.
Berger, M., Toussaint, F., Ben Djemaa, S., Maquoi, E., Pendeville, H., Evrard, B., Jerôme, C., Leblond Chain, J., Lechanteur, A., Mottet, D., Debuigne, A., Piel, G., Poly(N ‐methyl‐ N ‐vinylacetamide): a strong alternative to PEG for lipid‐based nanocarriers delivering siRNA. Adv. Healthc. Mater., 2023, 2302712, 10.1002/adhm.202302712.
Zard, S.Z., Discovery of the RAFT/MADIX process: mechanistic insights and polymer chemistry implications. Macromolecules 53 (2020), 8144–8159, 10.1021/acs.macromol.0c01441.
Perrier, S., 50th Anniversary perspective: RAFT polymerization - a user guide. Macromolecules 50 (2017), 7433–7447, 10.1021/acs.macromol.7b00767.
Hill, M.R., Carmean, R.N., Sumerlin, B.S., Expanding the scope of RAFT polymerization: recent advances and new horizons. Macromolecules 48 (2015), 5459–5469, 10.1021/acs.macromol.5b00342.
Tilottama, B., Manojkumar, K., Haribabu, P.M., Vijayakrishna, K., A short review on RAFT polymerization of less activated monomers. J. Macromol. Sci. Part A Pure Appl. Chem. 59 (2022), 180–201, 10.1080/10601325.2021.2024076.
Harrisson, S., Liu, X., Ollagnier, J.N., Coutelier, O., Marty, J.D., Destarac, M., RAFT polymerization of vinyl esters: Synthesis and applications. Polymers (Basel) 6 (2014), 1437–1488, 10.3390/polym6051437.
Roka, N., Kokkorogianni, O., Kontoes-Georgoudakis, P., Choinopoulos, I., Pitsikalis, M., Recent advances in the synthesis of complex macromolecular architectures based on poly(N-vinyl pyrrolidone) and the RAFT polymerization technique. Polym. (Basel), 14, 2022, 701, 10.3390/polym14040701.
McDowall, L., Chen, G., Stenzel, M.H., Synthesis of seven-arm poly(vinyl pyrrolidone) star polymers with lysozyme core prepared by MADIX/RAFT polymerization. Macromol. Rapid Commun. 29 (2008), 1666–1671, 10.1002/marc.200800416.
Langlais, M., Coutelier, O., Destarac, M., Thiolactone-functional reversible deactivation radical polymerization agents for advanced macromolecular engineering. Macromolecules 51 (2018), 4315–4324, 10.1021/acs.macromol.8b00770.
Pound, G., McKenzie, J.M., Lange, R.F.M., Klumperman, B., Polymer-protein conjugates from ω-aldehyde endfunctional poly(N-vinylpyrrolidone) synthesised via xanthate-mediated living radical polymerisation. Chem. Commun., 2008, 3193–3195, 10.1039/b803952f.
Dupre-Demorsy, A., Coutelier, O., Destarac, M., Nadal, C., Bourdon, V., Ando, T., Ajiro, H., RAFT polymerization of N-methyl-N-vinylacetamide and related double hydrophilic block copolymers. Macromolecules 55 (2022), 1127–1138, 10.1021/acs.macromol.1c01593.
Huynh, N.T., Passirani, C., Saulnier, P., Benoit, J.P., Lipid nanocapsules: a new platform for nanomedicine. Int. J. Pharm. 379 (2009), 201–209, 10.1016/j.ijpharm.2009.04.026.
B. Heurtault, P. Saulnier, J.-P. Benoit, J.-E. Proust, B. Pechn, J. Richard, Lipid Nanocapsules, methods of preparation and use as a medicament., FR2805761B1, 2022.
Zhong, Z., Feijen, J., Lok, M.C., Hennink, W.E., Christensen, L.V., Yockman, J.W., Kim, Y.-H., Kim, S.W., Low molecular weight linear polyethylenimine- b -poly(ethylene glycol)- b -polyethylenimine triblock copolymers: synthesis, characterization, and in vitro gene transfer properties. Biomacromolecules 6 (2005), 3440–3448, 10.1021/bm050505n.
Passirani, C., Barratt, G., Devissaguet, J.-P., Labarre, D., Interactions of nanoparticles bearing heparin or dextran covalently bound to poly(methyl methacrylate) with the complement system. Life Sci. 62 (1998), 775–785, 10.1016/S0024-3205(97)01175-2.
Ge, Z., Xie, D., Chen, D., Jiang, X., Zhang, Y., Liu, H., Liu, S., Stimuli-responsive double hydrophilic block copolymer micelles with switchable catalytic activity. Macromolecules 40 (2007), 3538–3546, 10.1021/ma070550i.
Peng, C., Huang, K., Han, M., Meng, W., Xiong, Y., Xu, W., Facile synthesis and catalytic activity of well-defined amphiphilic block copolymers based on N -vinylimidazolium. Polym. Adv. Technol. 24 (2013), 1089–1093, 10.1002/pat.3193.
Wamsley, A., Jasti, B., Phiasivongsa, P., Li, X., Synthesis of random terpolymers and determination of reactivity ratios ofN-carboxyanhydrides of leucine, ?-benzyl aspartate, and valine. J. Polym. Sci. Part A Polym. Chem. 42 (2004), 317–325, 10.1002/pola.11020.
Ting, J.M., Navale, T.S., Bates, F.S., Reineke, T.M., Precise compositional control and systematic preparation of multimonomeric statistical copolymers. ACS Macro Lett. 2 (2013), 770–774, 10.1021/mz4003112.
Fineman, M., Ross, S.D., Linear method for determining monomer reactivity ratios in copolymerization. J. Polym. Sci. 5 (1950), 259–262, 10.1002/pol.1950.120050210.
Kelen, T., Tudos, F., Analysis of the linear methods for determining copolymerization reactivity ratios. I. A new improved linear graphic method. J. Macromol. Sci. Part A - Chem. 9 (1975), 1–27, 10.1080/00222337508068644.
Vonarbourg, A., Saulnier, P., Passirani, C., Benoit, J.P., Electrokinetic properties of noncharged lipid nanocapsules: Influence of the dipolar distribution at the interface. Electrophoresis 26 (2005), 2066–2075, 10.1002/elps.200410145.
Hakamatani, T., Asayama, S., Kawakami, H., Synthesis of alkylated poly(1-vinylimidazole) for a new pH-sensitive DNA carrier. Nucleic Acids Symp. Ser. 52 (2008), 677–678, 10.1093/nass/nrn342.
Tarley, C.R.T., Corazza, M.Z., Somera, B.F., Segatelli, M.G., Preparation of new ion-selective cross-linked poly(vinylimidazole-co-ethylene glycol dimethacrylate) using a double-imprinting process for the preconcentration of Pb2+ ions. J. Colloid Interface Sci. 450 (2015), 254–263, 10.1016/j.jcis.2015.02.074.
Liu, G., Li, Y., Sheth, V.R., Pagel, M.D., Imaging in vivo extracellular pH with a single paramagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent. Mol. Imaging 11 (2012), 47–57 〈http://www.ncbi.nlm.nih.gov/pubmed/22418027〉.
Boussif, O., Lezoualc'h, F., Zanta, M.A., Mergny, M.D., Scherman, D., Demeneix, B., Behr, J.P., A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc. Natl. Acad. Sci. 92 (1995), 7297–7301, 10.1073/pnas.92.16.7297.
Asayama, S., Nishinohara, S., Kawakami, H., Zinc-chelated poly(1-vinylimidazole) and a carbohydrate ligand polycation form DNA ternary complexes for gene delivery. Bioconjug. Chem. 22 (2011), 1864–1868, 10.1021/bc2003378.
Vonarbourg, A., Passirani, C., Saulnier, P., Simard, P., Leroux, J.C., Benoit, J.P., Evaluation of pegylated lipid nanocapsules versus complement system activation and macrophage uptake. J. Biomed. Mater. Res. Part A. 78A (2006), 620–628, 10.1002/jbm.a.30711.
