Synthesis of poly(dimethylmalic acid) homo- and copolymers to produce biodegradable nanoparticles for drug delivery: Cell uptake and biocompatibility evaluation in human HepaRG hepatoma cells
[en] Hydrophobic and amphiphilic derivatives of the biocompatible and biodegradable poly(dimethylmalic acid) (PdiMeMLA), varying by the nature of the lateral chains and the length of each block, respectively, have been synthesized by anionic ring-opening polymerization (aROP) of the corresponding monomers using an initiator/base system, which allowed for very good control over the (co)polymers' characteristics (molar masses, dispersity, nature of end-chains). Hydrophobic and core-shell nanoparticles (NPs) were then prepared by nanoprecipitation of hydrophobic homopolymers and amphiphilic block copolymers, respectively. Negatively charged NPs, showing hydrodynamic diameters (Dh) between 50 and 130 nm and narrow size distributions (0.08 < PDI < 0.22) depending on the (co)polymers nature, were obtained and characterized by dynamic light scattering (DLS), zetametry, and transmission electron microscopy (TEM). Finally, the cytotoxicity and cellular uptake of the obtained NPs were evaluated in vitro using the hepatoma HepaRG cell line. Our results showed that both cytotoxicity and cellular uptake were influenced by the nature of the (co)polymer constituting the NPs.
Research center :
CIRMAP - Centre d'Innovation et de Recherche en Matériaux Polymères
Disciplines :
Chemistry
Author, co-author :
Khalil, Ali
Saba, Saad
Ribault, Catherine
Vlach, Manuel
Loyer, Pascal
Cammas-Marion, S.
Coulembier, Olivier ; Université de Mons > Faculté des Sciences > Matériaux Polymères et Composites
Language :
English
Title :
Synthesis of poly(dimethylmalic acid) homo- and copolymers to produce biodegradable nanoparticles for drug delivery: Cell uptake and biocompatibility evaluation in human HepaRG hepatoma cells
R550 - Institut des Sciences et Technologies de la Santé
Name of the research project :
élaboration de NANOparticules fonctionnelles à base de dérivés du poly(acide diméthylmalique) pour la VECTorisation ciblée de principes actifs et de gènes thérapeutiques. - Fédération Wallonie Bruxelles
Blanco, E.; Shen, H.; Ferrari, M. Principles of nanoparticles design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 2015, 33, 941-951.
Bobo, D.; Robinson, K.J.; Islam, J.; Thurecht, K.J.; Corrie, S.R. Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date. Pharm. Res. 2016, 33, 2373-2387.
Moghini, S.M.; Hunter, A.C.; Murray, J.C. Long-circulating and target-specific nanoparticles: Theory to practice. Pharmacol. Rev. 2001, 53, 283-318.
Arvizo, R.R.; Miranda, O.R.; Moyano, D.F.; Walden, C.A.; Giri, K.; Bhattacharya, R.; Robertson, J.D.; Rotello, V.M.; Reid, J.M.; Mukherjee, P. Modulating pharmacokinetics, tumor uptake and biodistribution by engineered nanoparticles. PLoS ONE 2011, 6, e24374.
Mahon, E.; Salvati, A.; Baldelli Bombelli, F.; Lynch, I.; Dawson, K.A. Designing the nanoparticles-biomolecule interface for "targeting and therapeutic delivery". J. Control. Release 2012, 262, 164-174.
Pearce, A.K.; O'Reilly, R.K. Insights into active targeting of nanoparticles in drug delivery: Advances in clinical studies and design considerations for cancer nanomedecine. Bioconjug. Chem. 2019, 30, 2300-2311.
Englert, C.; Brendel, J.C.; Majdanski, T.C.; Yildirim, T.; Schubert, S.; Gottschaldt, M.; Windhab, N.; Schubert, U.S. Pharmacopolymers in the 21st century: Synthetic polymers in drug delivery applications. Prog. Polym. Sci. 2018, 87, 107-164.
Venditto, V.J.; Szoka, F.C., Jr. Cancer nanomedicines: So many papers and so few drugs! Adv. Drug Deliv. Rev. 2013, 65, 80-88.
Khan, H.A.; Sakharkar, M.K.; Nayak, A.; Kishore, U.; Khan, A. Nanoparticles for biomedical applications: An overview. In Nanomaterials: Nanostructured Materials for Biomedical Applications; Narayan, R., Ed.; Woodhead publishing Series in Biomaterials; Elsevier Ltd.: Duxfort, UK, 2018; pp. 357-377.
Wicki, A.; Witzigmann, D.; Balasubramanian, V.; Huwyler, J. Nanomedicine in cancer therapy: Challenges, opportunities, and clinical applications. J. Control. Release 2015, 200, 138-157.
Copi, S.; Amalraj, A.; Sukumaran, N.P.; Haponiuk, J.T.; Thomas, S. Biopolymers and their composites for drug delivery: A brief overview. Macromol. Symp. 2018, 380, 1800114.
Chen, W.; Zhou, S.; Ge, L.; Wu, W.; Jiang, X. Translatable high drug loading drug delivery systems based on biocompatible polymers nanocarriers. Biomacromolecules 2018, 29, 1732-1742.
Nair, P.R. Delivering combination chemotherapies and targeting oncogenic pathways via polymeric drug delivery systems. Polymers 2019, 22, 630.
Loyer, P.; Cammas-Marion, S. Natural and synthetic poly(malic acid)-based derivates: A family of versatile biopolymers for the design of drug nanocarriers. J. Drug Target. 2014, 22, 556-575.
Casajus, H.; Saba, S.; Vlach, M.; Vène, E.; Ribault, C.; Tranchimand, S.; Nugier-Chauvin, C.; Dubreucq, E.; Loyer, P.; Cammas-Marion, S.; et al. Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary Macrophages. Polymers (Basel) 2018, 20, 1244.
Owens, D.E.; Peppas, N.A. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm. 2006, 307, 93-102.
Harris, J.M.; Chess, R.B. Effect of pegylation on pharmaceuticals. Nat. Rev. 2003, 2, 214-221.
Veronese, F.M. Peptide and protein PEGylation: A review of problems and solutions. Biomaterials 2001, 22, 405-417.
Kolate, A.; Baradia, D.; Patil, S.; Vhora, I.; Kore, G.; Misra, A. PEG-A versatile conjugating ligand for drugs and drug delivery systems. J. Control. Release 2014, 292, 67-81.
Liu, S.; Jiang, S. Chemical conjugation of zwitterionic polymers protects immunogenic enzyme and preserves bioactivity without polymer-specific antibody response. Nano Today 2016, 22, 285-291.
Armstrong, J.K.; Hempel, G.; Koling, S.; Chan, L.S.; Fisher, T.; Meiselman, H.J.; Garratty, G. Antibody against poly(ethylene glycol) adversely affects PEG-asparaginase therapy in acute lymphoblastic leukemia patients. Cancer 2007, 220, 103-111.
Dams, E.T.; Laverman, P.; Oyen, W.J.; Storm, G.; Scherphof, G.L.; van Der Meer, J.W.; Corstens, F.H.; Boerman, O.C. Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes. J. Pharmacol. Exp. Ther. 2000, 292, 1071-1079.
Kawai, F. Microbial degradation of polyethers. Appl. Microbiol. Biotechnol. 2002, 58, 30-38.
Huh, M.S.; Lee, E.J.; Koo, H.; Yhee, J.Y.; Oh, K.S.; Son, S.; Lee, S.; Kim, S.H.; Kwon, I.C.; Kim, K. Polysaccharide-Based Nanoparticles for Gene Delivery. Top. Curr. Chem. 2017, 375, 1-19.
Cammas, S.; Béar, M.M.; Harada, A.; Guérin, P.; Kataoka, K. New macromolecular micelles based on degradable amphiphilic block copolymers. Macromol. Chem. Phys. 2000, 201, 355-364.
Martinez Barbosa, M.E.; Cammas, S.; Appel, M.; Ponchel, G. Investigation of the degradation mechanisms of poly(malic acid) esters in vitro and their related cytotoxicities on J774 macrophages. Biomacromolecules 2004, 5, 137-143.
Barouti, G.; Khalil, A.; Orione, C.; Jarnouen, K.; Cammas-Marion, S.; Loyer, P.; Guillaume, S.M. Poly(trimethylene carbonate)/poly(malic acid) amphiphilic diblock copolymers as original biocompatible nanoparticles. Chem. Eur. J. 2016, 22, 2819-2830.
Zia, K.M.; Noreen, A.; Zuber, M.; Tabasum, S.; Mujahid, M. Recent Developments and Future Prospects on Bio-Based Polyesters Derived from Renewable Resources: A Review. Int. J. Biol. Macromol. 2016, 82, 1028-1040.
Ikada, Y.; Tsuji, H. Biodegradable Polyesters for Medical and Ecological Applications. Macromol. Rapid Commun. 2000, 21, 117-132.
Xu, M.; Yang, R.; Huang, Q.; Zhao, X.; Ma, C.; Li, W.; Li, J.; Liu, S. Preparation and characterization of acetylated Nanocrystalline cellulose-reinforced polylactide highly regular porous films. Bioresources 2018, 13, 8432-8443.
Manitchotpisit, P.; Skory, C.D.; Peterson, S.W.; Price, N.P.J.; Vermillion, K.E.; Leathers, T.D. Poly(ß-L-malic acid) production by diverse phylogenetic clades of Aureobasidium Pullulans. J. Ind. Microbiol. Biotechnol. 2012, 39, 125-132.
Hall, H.K., Jr.; Scheneider, A.K. Polymerization of cyclic esters, urethans, ureas and imides. J. Am. Chem. Soc. 1958, 80, 6409-6412.
Khalil, A.; Cammas-Marion, S.; Coulembier, O. Organocatalysis applied to the ring-opening polymerization of ß-lactones: A brief overview. J. Polym. Sci. Part A Polym. Chem. 2019, 57, 657-672.
Barbaud, C.; Guerrouache, M.; Guérin, P. Synthesis of novel
Barbaud, C.; Fay, F.; Abdillah, F.; Randriamahefa, S.; Guérin, P. Synthesis of new homopolyester and copolyesters by anionic ring-opening polymerization of
Ouhib, F.; Randriamahefa, S.; Guérin, P.; Barbaud, C. Synthesis of new statistical and block co-polyesters by ROP of a, a, ß-trisubstituted ß-lactones and their characterizations. Des. Monomers Polym. 2005, 8, 25-35.
Schott, M.A.; Domurado, M.; Leclercq, L.; Barbaud, C.; Domurado, D. Solubilization of water-insoluble drugs due to random amphiphilic and degradable poly(dimethylmalic acid) derivatives. Biomacromolecules 2013, 14, 1936-1944.
Belibel, R.; Barbaud, C. Synthesis and characterizations of hemiditactic homopolymers derived of poly(3-allyl-3-methylmalic acid): An example of a new class of polymer's ditacticity. J. Polym. Sci. Part A Polym. Chem. 2017, 55, 2408-2418.
Belibel, R.; Barbaud, C. Synthesis of new optically active
Tetraethylammonium. Available online: https://www.drugbank.ca/drugs/DB08837 (accessed on 2 November 2018).
Gripon, P.; Rumin, S.; Urban, S.; Le Seyec, J.; Glaise, D.; Cannie, I.; Guyomard, C.; Lucas, J.; Trepo, C.; Guguen-Guillouzo, C. Infection of a human hepatoma cell line by hepatitis B virus. Proc. Natl. Acad. Sci. USA 2002, 99, 15655-15660.
Cerec, V.; Glaise, D.; Garnier, D.; Morosan, S.; Turlin, B.; Drenou, B.; Gripon, P.; Kremsdorf, D.; Guguen-Guillouzo, C.; Corlu, A. Transdifferentiation of hepatocyte-like cells from the human hepatoma HepaRG cell line through bipotent progenitor. Hepatology 2007, 45, 957-967.
Corlu, A.; Loyer, P. Culture Conditions Promoting Hepatocyte Proliferation and Cell Cycle Synchronization. Methods Mol. Biol. 2015, 1250, 27-51.
Coulembier, O.; Degée, P.; Cammas-Marion, S.; Guérin, P.; Dubois, P. New amphiphilic poly[(R, S)-ß-malic acid-b-£-caprolactone] diblock copolymers by combining anionic and coordination-insertion ring-opening polymerization. Macromolecules 2002, 35, 9896-9903.
Zhang, L.; Nederberg, F.; Messman, J.M.; Pratt, R.C.; Hedrick, J.L.; Wade, C.G. Organocatalytic stereoselective ring-opening polymerization of lactide with dimeric phosphazene bases. J. Am. Chem. Soc. 2007, 129, 12610-12611.
Zhang, L.; Nederberg, F.; Pratt, R.C.; Waymouth, R.M.; Hedrick, J.L.; Wade, C.G. Phopsphazene bases: A new category of organocatalysts for the living ring-opening polymerization of cyclic esters. Macromolecules 2007, 40, 4154-4158.
De Winter, J.; Coulembier, O.; Gerbaux, P.; Dubois, P. High molecular weight poly(
Yang, H.; Xu, J.; Pispas, S.; Zhang, G. Hybrid copolymerization of £-caprolactone and methyl methacrylate. Macromolecules 2012, 45, 3312-3317.
Kawalec, M.; Coulembier, O.; Gerbaux, P.; Sobata, M.; De Winter, J.; Dubois, P.; Kowalczuk, M.; Kurcok, P. Trace do matter-Purity of 4-methyl-2-oxetanone and its effect on anionic ring-opening polymerization as evidence by phosphazene superbase catalysis. Reac. Funct. Polym. 2012, 72, 509-520.
Xu, J.; Yang, H.; Zhang, G. Synthesis of poly(e-caprolactone-co-methacrylic acid) copolymer via phosphazene-catalyzed hybrid copolymerization. Macromol. Chem. Phys. 2013, 214, 378-385.
Giammona, G.; Craparo, E.F. Biomedical applications of polylactide (PLA) and its copolymers. Molecules 2018, 23, 980.
Vène, E.; Barouti, G.; Jarnouen, K.; Gicquel, T.; Rauch, C.; Ribault, C.; Guillaume, S.M.; Cammas-Marion, S.; Loyer, P. Opsonisation of nanoparticles prepared from poly(ß-hydroxybutyrate) and poly(trimethylene carbonate)-b-poly(malic acid) amphiphilic diblock copolymers: Impact on the in vitro cell uptake by primary human macrophages and HepaRG hepatoma cells. Int. J. Pharm. 2016, 513, 38-452.
Caron, A.; Braud, C.; Bunel, C.; Vert, M. Blocky structure of copolymers obtained by Pd/C catalyzed hydrogenolysis of benzyl protecting groups as shown by sequence-selective hydrolytic degradation in poly(ß-malic acid) derivatives. Polymer 1990, 31, 1797-1802.
Kataoka, K.; Kwon, G.S.; Yokoyama, M.; Okano, T.; Sakurai, Y. Block copolymer micelles as vehicles for drug delivery. J. Control. Release 1993, 24, 119-132.
Thioune, O.; Fessi, H.; Devissaguet, J.P.; Puisieux, F. Preparation of pseudolatex by nanoprecipitation: Influence of the solvent nature on intrinsic viscosity and interaction constant. Int. J. Pharm. 1997, 146, 233-238.
Martinez Rivas, C.J.; Tarhini, M.; Badri, W.; Miladi, K.; Greige-Gerges, H.; Nazari, Q.A.; Galindo Rodriguez, S.A.; Román, R. Á.; Fessi, H.; Elaissari, A. Nanoprecipitation process: From encapsulation to drug delivery. Int. J. Pharm. 2017, 532, 66-81.
Msolli, I.; Belibel, R.; Chauvet, F.; Maaroufi, M.R.; Barbaud, C. Synthesis of nanoparticles based on PDMMLA derivative copolymers and study of warfarin encapsulation and controlled release. RCS Adv. 2017, 7, 6704-6711.
Bhattacharjee, S. DLS and zeta potential-What they are and what they are not? J. Control. Release 2016, 235, 337-351.
Limayem Blouza, I.; Charcosset, C.; Sfar, S.; Fessi, H. Preparation and characterization of spironolactone-loaded nanocapsules for paediatric use. Int. J. Pharm. 2006, 325, 124-131.
Aninat, C.; Piton, A.; Glaise, D.; Le Charpentier, T.; Langouet, S.; Morel, F.; Guguen-Guillouzo, C.; Guillouzo, A. Expression of cytochrome P450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells. DrugMetab. Dispos. 2006, 34, 75-83.
Quesnot, N.; Bucher, S.; Gade, C.; Vlach, M.; Vène, E.; Valenca, S.; Gicquel, T.; Holst, H.; Robin, M.A.; Loyer, P. Production of chlorzoxazone glucuronides via cytochrome P4502E1 dependent and independent pathways in human hepatocytes. Arch. Tox. 2018, 92, 3077-3091.
Vlach, M.; Quesnot, N.; Dubois-Pot-Schneider, H.; Ribault, C.; Verres, Y.; Petitjean, K.; Rauch, C.; Morel, F.; Robin, M.A.; Corlu, A.; et al. Cytochrome P450 1A1/2, 2B6 and 3A4 HepaRG Cell-Based Biosensors to Monitor Hepatocyte Differentiation, Drug Metabolism and Toxicity. Sensors (Basel) 2019, 19, 2245.
Huang, Z.H.; Laurent, V.; Chetouani, G.; Ljubimova, J.Y.; Holler, E.; Benvegnu, T.; Loyer, P.; Cammas-Marion, S. New functional degradable and bio-compatible nanoparticles based on poly(malic acid) derivatives for site-specific anti-cancer drug delivery. Int. J. Pharm. 2012, 423, 84-92.
Fröhlich, E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int. J. Nanomed. 2012, 7, 5577-5591.
