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Capsaicin-Loaded Chitosan Nanocapsules For WtCFTR-mRNA Delivery To A Cystic Fibrosis Cell Line

A. K. Kolonko, Janes Efing, Y. González-Espinosa, N. Bangel-Ruland, Willy van Driessche, F. Goycoolea, Wolf-Michael Weber
Published 2020 · Chemistry, Medicine

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Cystic fibrosis (CF), a lethal hereditary disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene coding for an epithelial chloride channel, is characterized by an imbalanced homeostasis of ion and water transports in secretory epithelia. As the disease is single-gene based, transcript therapy using therapeutic mRNA is a promising concept of treatment in order to correct many aspects of the fatal pathology on a cellular level. Hence, we developed chitosan nanocapsules surface-loaded with wtCFTR-mRNA to restore CFTR function. Furthermore, we loaded the nanocapsules with capsaicin, aiming to enhance the overall efficiency of transcript therapy by reducing sodium hyperabsorption by the epithelial sodium channel (ENaC). Dynamic light scattering with non-invasive back scattering (DLS-NIBS) revealed nanocapsules with an average hydrodynamic diameter of ~200 nm and a Zeta potential of ~+60 mV. The results of DLS-NIBS measurements were confirmed by asymmetric flow field-flow fractionation (AF4) with multidetection, while transmission electron microscopy (TEM) images confirmed the spherical morphology and size range. After stability measurements showed that the nanocapsules were highly stable in cell culture transfection medium, and cytotoxicity was ruled out, transfection experiments were performed with the CF cell line CFBE41o-. Finally, transepithelial measurements with a new state-of-the-art Ussing chamber confirmed successfully restored CFTR function in transfected cells. This study demonstrates that CS nanocapsules as a natural and non-toxic delivery system for mRNA to target cells could effectively replace risky vectors for gene delivery. The nanocapsules are not only suitable as a transcript therapy for treatment of CF, but open aspiring possibilities for safe gene delivery in general.
This paper references
10.1002/jgm.2748
Cystic fibrosis transmembrane conductance regulator‐mRNA delivery: a novel alternative for cystic fibrosis gene therapy
N. Bangel-Ruland (2013)
10.1016/j.ymthe.2019.02.012
Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery.
Piotr S Kowalski (2019)
10.1177/039463201302600303
Impact of Capsaicin on Mast Cell Inflammation
S. Frydas (2013)
10.1165/2009-0147OC
AMPK agonists ameliorate sodium and fluid transport and inflammation in cystic fibrosis airway epithelial cells.
M. Myerburg (2010)
10.1016/j.addr.2009.08.004
Chitosan-based formulations for delivery of DNA and siRNA.
S. Mao (2010)
10.2217/17435889.3.4.437
Characterization of superparamagnetic iron oxide nanoparticles by asymmetrical flow-field-flow-fractionation.
Jessica Lohrke (2008)
10.1016/j.jcf.2018.05.004
CFTR modulator theratyping: Current status, gaps and future directions.
J. Clancy (2019)
10.1016/j.jfda.2015.01.001
Formulation of essential oil-loaded chitosan-alginate nanocapsules.
Dheebika Natrajan (2015)
10.2174/156652312802762536
mRNA as a versatile tool for exogenous protein expression.
A. Kuhn (2012)
10.1007/s00216-008-2319-y
Particle size characterization by quadruple-detector hydrodynamic chromatography
Amandaa K. Brewer (2009)
10.3390/polym10040444
Chitosan in Non-Viral Gene Delivery: Role of Structure, Characterization Methods, and Insights in Cancer and Rare Diseases Therapies
Beatriz Santos-Carballal (2018)
10.1016/S1773-2247(06)50061-9
Chitosan nanocapsules: a new carrier for nasal peptide delivery
C. Prego (2006)
10.1080/01932690208984202
Spontaneous Emulsification: Mechanisms, Physicochemical Aspects, Modeling, and Applications
Juan C. López-Montilla (2002)
10.1023/A:1011037807261
Water-Soluble and Low Molecular Weight Chitosan-Based Plasmid DNA Delivery
M. Lee (2004)
10.1038/39807
The capsaicin receptor: a heat-activated ion channel in the pain pathway
M. Caterina (1997)
10.1016/J.BIOMATERIALS.2005.09.020
Characterization of folate-chitosan-DNA nanoparticles for gene therapy.
Sania Mansouri (2006)
10.1515/cclm-2015-1151
Reduced absorption and enhanced synthesis of cholesterol in patients with cystic fibrosis: a preliminary study of plasma sterols
Monica Gelzo (2016)
10.1023/B:PHAM.0000012150.60180.e3
Effect of Chitosan on Epithelial Cell Tight Junctions
J. Smith (2004)
10.1038/nm.2715
Cystic fibrosis: a mucosal immunodeficiency syndrome
T. Cohen (2012)
10.3390/pharmaceutics12070652
Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity
Nabil A Alhakamy (2020)
10.1016/j.jcf.2017.06.011
Pancreatic insufficiency in Cystic Fibrosis.
V. Singh (2017)
10.1023/A:1010067107182
Dynamic Light Scattering Measurement of Nanometer Particles in Liquids
R. Pécora (2000)
10.1038/NG0992-21
Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis
L. G. Johnson (1992)
10.1039/c4cs00487f
Nanoparticle colloidal stability in cell culture media and impact on cellular interactions.
T. Moore (2015)
10.1016/J.JCONREL.2004.07.030
Transmucosal macromolecular drug delivery.
C. Prego (2005)
10.1016/j.ijbiomac.2019.06.122
Characterisation of chitosan molecular weight distribution by multi-detection asymmetric flow-field flow fractionation (AF4) and SEC.
Y. González-Espinosa (2019)
10.1165/RCMB.2001-0004OC
Five percent of normal cystic fibrosis transmembrane conductance regulator mRNA ameliorates the severity of pulmonary disease in cystic fibrosis.
A. Ramalho (2002)
10.1016/j.jcf.2013.12.002
Rate of improvement of CF life expectancy exceeds that of general population—Observational death registration study☆☆☆
M. Hurley (2014)
10.1093/bja/aeq067
Pharmacology of capsaicin-, anandamide-, and N-arachidonoyl-dopamine-evoked cell death in a homogeneous transient receptor potential vanilloid subtype 1 receptor population.
J. Davies (2010)
10.1016/j.colsurfb.2010.10.019
Chitosan nanocapsules: Effect of chitosan molecular weight and acetylation degree on electrokinetic behaviour and colloidal stability.
M. J. Santander-Ortega (2011)
10.1016/j.ijpharm.2016.01.083
Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line.
Elena Fernández Fernández (2016)
10.3390/ma11010122
Biopolymer-Based Nanoparticles for Cystic Fibrosis Lung Gene Therapy Studies
Elena Fernández Fernández (2018)
10.1021/ac501664t
Asymmetric flow field-flow fractionation in the field of nanomedicine.
M. Wagner (2014)
10.1007/s00018-016-2393-9
Cystic fibrosis: a clinical view
C. Castellani (2016)
10.1038/srep13567
Physicochemical and biological characterization of chitosan-microRNA nanocomplexes for gene delivery to MCF-7 breast cancer cells
B. Santos-Carballal (2015)
10.1016/J.CACC.2008.07.003
Capsaicin: A review of its pharmacology and clinical applications
M. Hayman (2008)
10.1113/jphysiol.2012.240861
Does epithelial sodium channel hyperactivity contribute to cystic fibrosis lung disease?
Carey A. Hobbs (2013)
10.1152/ajplung.00142.2010
Regulation of endogenous ENaC functional expression by CFTR and ΔF508-CFTR in airway epithelial cells.
R. Rubenstein (2011)
10.1586/14760584.2015.973859
mRNA transcript therapy
D. Weissman (2015)
10.3390/nano8090659
Lower-Sized Chitosan Nanocapsules for Transcutaneous Antigen Delivery
Juan I. Bussio (2018)
10.1016/j.cell.2009.09.028
Cellular and Molecular Mechanisms of Pain
A. Basbaum (2009)
10.3389/fphar.2018.01475
Animal Models in the Pathophysiology of Cystic Fibrosis
Anna Semaniakou (2019)
10.1152/ajplung.00031.2011
Physiological effect of protein kinase C on ENaC-mediated lung liquid regulation in the adult rat lung.
B. Soukup (2012)
10.1007/s00396-012-2669-z
Chitosan-based nanocapsules: physical characterization, stability in biological media and capsaicin encapsulation
F. Goycoolea (2012)
10.1165/AJRCMB.10.1.7507342
CFTR expression and chloride secretion in polarized immortal human bronchial epithelial cells.
A. Cozens (1994)
10.1007/s40265-018-0982-7
Capsaicin 8% Dermal Patch: A Review in Peripheral Neuropathic Pain
H. Blair (2018)
10.1038/sj.bjp.0705467
Anandamide and vanilloid TRPV1 receptors
R. Ross (2003)
10.1515/jcim-2015-0037
Phytochemistry and gastrointestinal benefits of the medicinal spice, Capsicum annuum L. (Chilli): a review
A. K. Maji (2016)
10.14639/0392-100X-1328
An "ex vivo model" contributing to the diagnosis and evaluation of new drugs in cystic fibrosis
A. Di Lullo (2017)
10.1155/2014/789591
A Proteomic View to Characterize the Effect of Chitosan Nanoparticle to Hepatic Cells: Is Chitosan Nanoparticle an Enhancer of PI3K/AKT1/mTOR Pathway?
M. Yang (2014)
10.1016/J.JCONREL.2005.05.004
Transfection efficiency of chitosan vectors: effect of polymer molecular weight and degree of deacetylation.
M. Huang (2005)
10.1016/j.matpr.2020.01.491
Process optimization by response surface methodology for preparation and evaluation of methotrexate loaded chitosan nanoparticles
N. Naveen (2020)
10.1161/HYPERTENSIONAHA.114.03105
Transient Receptor Potential Vanilloid 1 Activation by Dietary Capsaicin Promotes Urinary Sodium Excretion by Inhibiting Epithelial Sodium Channel &agr; Subunit–Mediated Sodium Reabsorption
L. Li (2014)
10.1016/j.jaci.2013.08.026
Capsaicin treatment reduces nasal hyperreactivity and transient receptor potential cation channel subfamily V, receptor 1 (TRPV1) overexpression in patients with idiopathic rhinitis.
L. Van Gerven (2014)
10.1371/journal.pone.0079954
The Reversible Increase in Tight Junction Permeability Induced by Capsaicin Is Mediated via Cofilin-Actin Cytoskeletal Dynamics and Decreased Level of Occludin
T. Shiobara (2013)
10.1016/j.ymthe.2018.05.014
Lipid Nanoparticle-Delivered Chemically Modified mRNA Restores Chloride Secretion in Cystic Fibrosis.
E. Robinson (2018)
10.1016/J.JCIS.2006.12.075
Measurement and interpretation of electrokinetic phenomena.
Á. Delgado (2007)
10.3390/biom10040553
Chitosan Nanocomplexes for the Delivery of ENaC Antisense Oligonucleotides to Airway Epithelial Cells
A. K. Kolonko (2020)
10.1016/S0032-3861(99)00472-3
Light scattering studies on core-shell systems: determination of size parameters of sterically stabilized poly(methylmethacrylate) dispersions
B. Hirzinger (2000)
10.3390/md18040226
Chitosan Coated Microparticles Enhance Simvastatin Colon Targeting and Pro-Apoptotic Activity
Nabil A Alhakamy (2020)
10.1016/j.jconrel.2014.11.019
Cancer-targeted MDR-1 siRNA delivery using self-cross-linked glycol chitosan nanoparticles to overcome drug resistance.
J. Y. Yhee (2015)
10.1038/nrd4278
mRNA-based therapeutics — developing a new class of drugs
U. Şahin (2014)
10.1080/07391102.2018.1445559
Design of functionalized folic acid–chitosan nanoparticles for delivery of tetracycline, doxorubicin, and tamoxifen
P. Chanphai (2019)
10.1371/journal.pone.0141017
In Vitro and Sensory Evaluation of Capsaicin-Loaded Nanoformulations
Mathias Kaiser (2015)
10.1371/journal.pbio.1000155
CFTR Delivery to 25% of Surface Epithelial Cells Restores Normal Rates of Mucus Transport to Human Cystic Fibrosis Airway Epithelium
L. Zhang (2009)
10.1186/s41231-016-0006-0
Optimization of CFTR-mRNA transfection in human nasal epithelial cells
Elena Fernández Fernández (2016)
10.3390/molecules21070844
Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses
V. Fattori (2016)
10.1007/S003960050050
Development of positively charged colloidal drug carriers: Chitosan-coated polyester nanocapsules and submicron-emulsions
P. Calvo (1997)
10.1016/j.carbpol.2016.11.027
Co-delivery of antineoplastic and protein drugs by chitosan nanocapsules for a collaborative tumor treatment.
Dong-Yan Wu (2017)
10.1038/s41598-018-34960-0
Chemically modified hCFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis
A. K. M. Ashiqul Haque (2018)
10.1016/j.ejpb.2012.09.010
Low molecular weight oligochitosans for non-viral retinal gene therapy.
G. Puras (2013)
10.1038/srep10048
Chitosan encapsulation modulates the effect of capsaicin on the tight junctions of MDCK cells
M. Kaiser (2015)
10.1088/0957-4484/22/1/015101
Formulation of chitosan-TPP-pDNA nanocapsules for gene therapy applications.
V. Gaspar (2011)
10.1016/j.antiviral.2016.04.010
Development of antiviral gene therapy for Monodon baculovirus using dsRNA loaded chitosan-dextran sulfate nanocapsule delivery system in Penaeus monodon post-larvae.
D. Ramesh kumar (2016)
10.1016/J.AJPS.2013.07.001
The endocytosis and intracellular fate of nanomedicines: Implication for rational design
L. Kou (2013)



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