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Nanoparticle-loaded Hydrogels as a Pathway for Enzyme-triggered Drug Release in Ophthalmic Applications
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. (Nanotechnology and functional materials)ORCID iD: 0000-0001-7638-0925
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
2017 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476Article in journal (Refereed) In press
Abstract [en]

The aim of this study was to develop nanoparticle loaded hydrogel based contact lenses that could be used for ocular drug delivery. Two potential contact lens platforms for controlled ophthalmic drug delivery were developed by incorporating chitosan-poly(acrylic acid) nanoparticles into polyvinyl alcohol (PVA) hydrogels and in-situ gelled nanoparticles and cellulose nanocrystals (CNC) in PVA lenses. The nanoparticles were shown to disintegrate in a physiological 0.2 mM concentration of lysozyme resulting from the hydrolysis of the chitosan chains by lysozyme. An extended release over a 28-hour period was demonstrated once the nanoparticles had been integrated into the composite lenses, with nanoparticle-CNC PVA lenses showing even greater potential for extended release. The platform shows great promise in developing enzyme-triggered ocular drug delivery systems.

Place, publisher, year, edition, pages
Elsevier, 2017.
Keywords [en]
Nanoparticles, PVA, Chitosan, Drug delivery, Ophthalmic
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
URN: urn:nbn:se:uu:diva-334710OAI: oai:DiVA.org:uu-334710DiVA, id: diva2:1160398
Funder
Knut and Alice Wallenberg FoundationAvailable from: 2017-11-27 Created: 2017-11-27 Last updated: 2018-03-19
In thesis
1. Hydrogels of Poly(vinyl alcohol) and Nanocellulose for Ophthalmic Applications: Synthesis, Characterization, Biocompatibility and Drug Delivery Studies
Open this publication in new window or tab >>Hydrogels of Poly(vinyl alcohol) and Nanocellulose for Ophthalmic Applications: Synthesis, Characterization, Biocompatibility and Drug Delivery Studies
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hydrogels are commonly used materials in ophthalmic care as contact lenses, bandage lenses, corneal implants, and cornea regeneration scaffolds. Hydrogels can be produced by physical, chemical, or radiation crosslinking of hydrophilic polymers. Poly(vinyl alcohol) (PVA) is a hydrophilic polymer that has been long known to the scientific community and is used in ophthalmic formulations.

In this thesis, PVA was reinforced with nanocellulose to obtain self-standing hydrogels. Cryo-gelation technique was used to obtain transparent hydrogels from PVA dissolved in DMSO-water mixed solvent. The properties of these hydrogels were analyzed to explore the possibility of their application for ophthalmic use as a drug delivery vehicle and as cornea regeneration implant.

The results indicate that oxidized nanocellulose can be combined with PVA to produce transparent, elastic, macroporous and high-water content hydrogel lenses. The water-filled macroporous structure of these hydrogels aids with oxygen transport and can enhance comfort while worn. The developed hydrogel also features moderate UV-light blocking properties in addition to high transparency. Furthermore, it was observed that the light scattering due to surface roughness of the hydrogel increases with measurement time, due to the rapid evaporation of the water layer from the surface of the hydrogel film.

Mechanical analysis results revealed that the hydrogels exhibited a strain-induced stiffening behavior, which is usually noticed in hyper-elastic materials and collagenous soft tissues. The results of this study suggest that in order to mimic collagenous behavior, the material should possess high water content and a specific structural architecture combining soft and rigid elements as building blocks.

Furthermore, PVA-CNC composite hydrogel showed no toxic effects on the corneal cells in both direct and indirect contact studies. It was found that the hydrogel promoted cell attachment and was stable when sutured ex vivo to a porcine excised cornea.

To study enzyme-triggered drug release, hydrogel lenses loaded with chitosan-poly(acrylic acid) nanoparticles were exposed to lysozyme, an enzyme present in the eye. Nanoparticles were shown to disintegrate due to the hydrolysis of chitosan chains by lysozyme. Overall, with these distinctive properties, PVA-CNC hydrogel has great potential as an ophthalmic biomaterial for therapeutic and cornea regeneration applications. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 76
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1650
Keywords
nanocellulose, poly(vinyl alcohol), hydrogel, cornea regeneration, therapeutic lens
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-346478 (URN)978-91-513-0285-0 (ISBN)
Public defence
2018-05-17, Polhemssalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:30 (English)
Opponent
Supervisors
Available from: 2018-04-17 Created: 2018-03-19 Last updated: 2018-10-08

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