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Bioadhesive Hyaluronan–chitosan Nanoparticles Can Transport Genes Across The Ocular Mucosa And Transfect Ocular Tissue
M. Fuente, B. Seijo, M. J. Alonso
Published 2008 · Biology, Medicine
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Gene transfer is considered to be a promising alternative for the treatment of several chronic diseases that affect the ocular surface. The goal of the present work was to investigate the efficacy and mechanism of action of a novel DNA nanocarrier made of hyaluronan (HA) and chitosan (CS), specifically designed for topical ophthalmic gene therapy. With this goal in mind, we first evaluated the transfection efficiency of the plasmid DNA-loaded nanoparticles in a human corneal epithelium cell model. Second, we investigated the bioadhesion and internalization of the nanoparticles in the rabbit ocular epithelia by confocal laser scanning microscopy. Third, we determined the in vivo efficacy of these nanocarriers in terms of their ability to transfect ocular tissues. The results showed that HA–CS nanoparticles and, in particular, those made of low molecular weight CS (10–12 kDa), led to high levels of expression of secreted alkaline phosphatase in the human corneal epithelium model. In addition, we observed that, following topical administration to rabbits, these nanoparticles entered the corneal and conjunctival epithelial cells and, then, become assimilated by the cells. More importantly, these nanoparticles provided an efficient delivery of the associated plasmid DNA inside the cells, reaching significant transfection levels. Therefore, we conclude that these nanoparticles may represent a new strategy toward the gene therapy of several ocular diseases.
This paper references
The hyaluronan receptor (CD44) participates in the uptake and degradation of hyaluronan
M. Culty (1992)
Chitosan Nanoparticles as New Ocular Drug Delivery Systems: In Vitro Stability, in Vivo Fate, and Cellular Toxicity
A. Campos (2005)
A Look to Future Directions in Gene Therapy Research for Monogenic Diseases
M. Porteus (2006)
Cell culture models of the ocular barriers.
M. Hornof (2005)
Nuclear import of glycoconjugates is distinct from the classical NLS pathway.
É. Duverger (1995)
DNA-based therapeutics and DNA delivery systems: A comprehensive review
S. Patil (2008)
Culture model of human corneal epithelium for prediction of ocular drug absorption.
E. Toropainen (2001)
Recent developments in ocular gene therapy.
T. Borrás (2003)
Novel hyaluronic acid-chitosan nanoparticles for ocular gene therapy.
M. de la Fuente (2008)
Preparation and properties of fluorescein-labelled hyaluronate.
A. de Belder (1975)
Ocular delivery of nucleic acids: antisense oligonucleotides, aptamers and siRNA.
E. Fattal (2006)
Gene delivery to the eye using adeno-associated viral vectors.
Keith R G Martin (2002)
Expression of adhesion molecule CD44 on human corneas
S. N. Zhu (1997)
Efficient Non-Viral Ocular Gene Transfer with Compacted DNA Nanoparticles
R. Farjo (2006)
Gene transfer with liposomes to the intraocular tissues by different routes of administration
増田 郁也 (1997)
Improved chitosan-mediated gene delivery based on easily dissociated chitosan polyplexes of highly defined chitosan oligomers
M. Köping-Höggård (2004)
Hyaluronic acid and its derivative as a multi-functional gene expression enhancer: protection from non-specific interactions, adhesion to targeted cells, and transcriptional activation.
T. Ito (2006)
Inhibition of corneal neovascularization with endostatin delivered by adeno-associated viral (AAV) vector in a mouse corneal injury model.
L. Lai (2007)
Preparation and properties of fluorescein-labelled hyaluronate
AN DeBelder (1975)
Hyaluronan in the Treatment of Ocular Surface Disorders
P. Aragona (2004)
Novel hydrophilic chitosan‐polyethylene oxide nanoparticles as protein carriers
P. Calvo (1997)
The six hyaluronidase-like genes in the human and mouse genomes.
A. B. Csóka (2001)
Corneal epithelium as a platform for secretion of transgene products after transfection with liposomal gene eyedrops
E. Toropainen (2007)
Cationic Vectors in Ocular Drug Delivery
L. Rabinovich-Guilatt (2004)
Study of the mechanism of interaction of poly(ϵ-caprolactone) nanocapsules with the cornea by confocal laser scanning microscopy
P. Calvo (1994)
Endogenous hyaluronan in the anterior segment of the eye
P. Fagerholm (1996)
Corneal gene therapy.
E. Klausner (2007)
Gene therapy in the cornea
R. Mohan (2005)
Gene therapy in immune-mediated diseases of the eye
U. Pleyer (2003)
Gene therapy for ocular disease.
J. Bennett (2000)
Novel hyaluronan-based nanocarriers for transmucosal delivery of macromolecules.
M. de la Fuente (2008)
Dichotomy between survival and lytic gene expression in RNase L- and PKR-deficient mice transduced with an adenoviral vector expressing murine IFN-beta following ocular HSV-1 infection.
Khaldun Al-khatib (2005)
Nanoparticular Carriers for Ocular Drug Delivery
A. Sánchez (2006)
Improved Ocular Bioavailability of Indomethacin by Novel Ocular Drug Carriers
P. Calvo (1996)
Intracellular Localization of Hyaluronan in Proliferating Cells
S. Evanko (1999)
The effect of a PEG versus a chitosan coating on the interaction of drug colloidal carriers with the ocular mucosa.
A. M. de Campos (2003)
In vivo gene delivery into ocular tissues by eye drops of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles
J. Liaw (2001)
The potential of chitosan in ocular drug delivery
M. Alonso (2003)
Corneal Endothelial Hyaluronidase: A Role in Anterior Chamber Hyaluronic Acid Catabolism
D. Schwartz (1997)
Depolymerized chitosan nanoparticles for protein delivery: Preparation and characterization
Kevin A. Janes (2003)
Reduction of cardiovascular side effects associated with ocular administration of metipranolol by inclusion in polymeric nanocapsules.
C. Losa (1992)
Hyaluronidase and its substrate hyaluronan: biochemistry, biological activities and therapeutic uses.
E. Menzel (1998)
Hyaluronan and CD44 in the human cornea and limbal conjunctiva.
L. Lerner (1998)
Potential of low molecular mass chitosan as a DNA delivery system: biocompatibility, body distribution and ability to complex and protect DNA.
S. Richardson (1999)
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Triple combination of siRNAs targeting TGFβ1, TGFβR2, and CTGF enhances reduction of collagen I and smooth muscle actin in corneal fibroblasts.
Sriniwas Sriram (2013)
Chitosan‐Based Systems for Mucosal Delivery of Biopharmaceuticals
Sonia Al-Qadi (2012)
One-year follow-up of epithelial corneal cell sheet allografts mounted on platelet poor plasma in rabbits
Federico Luengo Gimeno (2009)
Chitosan-Polylactide/Hyaluronic Acid Complex Microspheres as Carriers for Controlled Release of Bioactive Transforming Growth Factor-β1
Qing Min (2018)
Ionically crosslinked chitosan/tripolyphosphate nanoparticles for oligonucleotide and plasmid DNA delivery.
N. Csaba (2009)
Silencing of hepatitis C virus replication by a non-viral vector based on solid lipid nanoparticles containing a shRNA targeted to the internal ribosome entry site (IRES).
J. Torrecilla (2016)
Understanding the influence of surface properties of nanoparticles and penetration enhancers for improving bioavailability in eye tissues in vivo.
Binapani Mahaling (2016)
A nanomedicine to treat ocular surface inflammation: performance on an experimental dry eye murine model
L. Contreras-Ruiz (2013)
Combining hyaluronic acid with chitosan enhances gene delivery
A. V. Oliveira (2014)
Nanomedicine for the treatment of retinal and optic nerve diseases.
M. Zarbin (2013)
Polymeric nanocapsules: a potential new therapy for corneal wound healing
S. Reimondez-Troitiño (2016)
Development of chitosan nanoparticles coated with hyaluronic acid for topical ocular delivery of dexamethasone.
M. A. Kalam (2016)
Sweet Fairytale: Carbohydrates as Backbones for Glyconanomedicine
Shoshy Mizrahy (2013)
The Design of Novel Nano-Sized Polyanion-Polycation Complexes for Oral Protein Delivery
Ambreen Khan (2014)
Trimethyl chitosan-hyaluronic acid nano-polyplexes for intravitreal VEGFR-2 siRNA delivery: Formulation and in-vivo efficacy evaluation.
Farkhondeh Chaharband (2020)
Topical Administration of SLN-Based Gene Therapy for the Treatment of Corneal Inflammation by De Novo IL-10 Production
M. Vicente-Pascual (2020)
Chitosan-coated PLGA nanoparticles of bevacizumab as novel drug delivery to target retina: optimization, characterization, and in vitro toxicity evaluation
J. Pandit (2017)
Mucoadhesive Polymers for Enhancing Retention in Ocular Drug Delivery
Anubha Khare (2015)
Bioadhesive Polymers for Drug Delivery
Eneko Larrañeta (2017)
Polymeric nanoparticulate system: a potential approach for ocular drug delivery.
R. C. Nagarwal (2009)
Nano-Biomaterials For Ophthalmic Drug Delivery
Y. Pathak (2016)
Versatility of chitosan/BmNPV bacmid DNA nanocomplex as transfection reagent of recombinant protein expression in silkworm larvae
T. Kato (2016)
Chitin and chitosan hydrogels
R.A.A. Muzzarelli (2009)
19 Chitosan-DNA / siRNA Nanoparticles for Gene Therapy
Qin Shi (2012)
Toxicity of nanomaterials to the eye.
T. Prow (2010)
Emerging roles of hyaluronic acid bioscaffolds in tissue engineering and regenerative medicine.
M. Hemshekhar (2016)
Dynamic bio-adhesion of polymer nanoparticles on MDCK epithelial cells and its impact on bio-membranes, endocytosis and paracytosis.
Bing He (2016)
Blends and composites of exopolysaccharides; properties and applications: A review.
A. Hussain (2017)
Preparation and characterization of nanoparticles from quaternized cyclodextrin-grafted chitosan associated with hyaluronic acid for cosmetics
Sakhiran Sakulwech (2018)
Dual Drug-Loaded Electrospun Nanofibres for the Treatment of Corneal Diseases
E. Tawfik (2019)
Hydration forces as a tool for the optimization of core–shell nanoparticle vectors for cancer gene therapy
Manuel J. Santander-Ortega (2012)
Mucoadhesive Systems: Drug Delivery
Ryan Francis Donnelly (2017)See more