DNA delivery from photocrosslinked PEG hydrogels: encapsulation efficiency, release profiles, and DNA quality

Quick, Deborah J.; Anseth, Kristi S.

doi:10.1016/j.jconrel.2004.01.021

Cited by 129 publications

(104 citation statements)

References 29 publications

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“…This degradation would reduce the cross-link density and increase the mesh size, thereby increasing transport through the hydrogel. Increasing the quantity of degradable segments will decrease the stability of the hydrogel, yet will increase transport through the hydrogel and thus increase the quantity released [11]. These observations have been reported previously with PEG-based hydrogels containing hydrolytically degradable PLA (poly lactic acid) linkages, which provide a sustained release based on the hydrolysis of the lactic acid segments [11].…”

Section: Discussionsupporting

confidence: 69%

“…When investigated by gel electrophoresis, plasmid released from the PEG/HA hydrogels had two distinct bands pertaining to both the supercoiled and relaxed forms, with both forms known to be transfection competent [11]. Previous studies investigating plasmid integrity in photopolymerized hydrogels indicate that radicals formed by the photoinitiator can damage plasmids when crosslinked with long range UV light [11].…”

Section: Discussionmentioning

confidence: 99%

“…3). In all cases, two distinct bands appeared, representing the relaxed and supercoiled forms of the DNA, both of which are transfection competent [11].…”

Section: Plasmid Releasementioning

confidence: 92%

“…For gene delivery in particular, localized release of plasmid or DNA complexes can transfect cells for the sustained production of tissue inductive proteins [9,10]. Hydrogels formed from a range of polymers have been employed for the controlled release non-viral vectors, such as naked plasmid or cationic polymer/DNA complexes [4,[11][12][13][14][15][16]. For many hydrogels, release occurs primarily by diffusion, which can be influenced by physical properties such as water content, swelling ratio, and mesh size.…”

Section: Introductionmentioning

confidence: 99%

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Non-viral vector delivery from PEG-hyaluronic acid hydrogels

Wieland

Houchin-Ray

Shea

2007

Journal of Controlled Release

121

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Hydrogels have been widely used in tissue engineering as a support for tissue formation or to deliver non-viral gene therapy vectors locally. Hydrogels that combine these functionalities can provide a fundamental tool to promote specific cellular processes leading to tissue formation. This report investigates controlled release of gene therapy vectors from hydrogels as a function of the physical properties for both the hydrogel and the vector. Hydrogels were formed by photocrosslinking acrylmodified hyaluronic acid (HA) with a 4-arm poly(ethylene glycol) (PEG) acryl. The polymer content, and relative composition of HA and PEG modulated the swelling ratio, water content, and degradation, which can influence transport of the vector through the hydrogel. All hydrogels had a water content of 94% or higher, though the water content and swelling ratio increased with a decrease in the PEG:HA ratio. Plasmids were stably incorporated into the hydrogel, with a majority of the release occurring during the initial 2 days. For incubation in buffer, the cumulative release increased with a decreasing PEG or increasing HA content, with approximately 20% to 80% released during the first week depending on the hydrogel composition. Hydrogels incubated in hyaluronidase, an enzyme that degrades HA, significantly increased plasmid release for hydrogels containing 4% PEG and 4% HA-Acryl. The encapsulation of plasmid complexed with polyethylenimine had less than 14% of the complexes released from the hydrogel both in the presence and absence of hyaluronidase. The limited release of the complexes likely results from the complex size and interactions between the vector and hydrogel. These studies demonstrate the dependence of non-viral vector release on the physical properties of the hydrogel and the vector, suggesting vector and hydrogel designs for maximizing localized delivery of non-viral vectors.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

“…3). In all cases, two distinct bands appeared, representing the relaxed and supercoiled forms of the DNA, both of which are transfection competent [11].…”

Section: Plasmid Releasementioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Non-viral vector delivery from PEG-hyaluronic acid hydrogels

Wieland

Houchin-Ray

Shea

2007

Journal of Controlled Release

121

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“…Naked DNA has been successfully incorporated inside hydrogels composed of collagen (18), pluronic-hyaluronic acid (19), dimethacrylated poly(lactic acid)-bpoly(ethylene glycol)-b-poly(lactic acid) triblock copolymers (20), alginate (21), oligo(polyethylene glycol) fumarate (22), and engineered silk elastin (23). Although naked DNA has shown gene expression and ability to guide regeneration in vivo (18,24), limitations with low gene transfer efficiency and rapid diffusion of the DNA from the hydrogel scaffold motivated the use of DNA nanoparticles instead of naked DNA.…”

Section: Introductionmentioning

confidence: 99%

Surface- and Hydrogel-Mediated Delivery of Nucleic Acid Nanoparticles

Pannier

Segura

2012

Nanotechnology for Nucleic Acid Delivery

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Gene expression within a cell population can be directly altered through gene delivery approaches. Traditionally for nonviral delivery, plasmids or siRNA molecules, encoding or targeting the gene of interest, are packaged within nanoparticles. These nanoparticles are then delivered to the media surrounding cells seeded onto tissue culture plastic; this technique is termed bolus delivery. Although bolus delivery is widely utilized to screen for efficient delivery vehicles and to study gene function in vitro, this delivery strategy may not result in efficient gene transfer for all cell types or may not identify those delivery vehicles that will be efficient in vivo. Furthermore, bolus delivery cannot be used in applications where patterning of gene expression is needed. In this chapter, we describe methods that incorporate material surfaces (i.e., surface-mediated delivery) or hydrogel scaffolds (i.e., hydrogel-mediated delivery) to efficiently deliver genes. This chapter includes protocols for surface-mediated DNA delivery focusing on the simplest and most effective methods, which include nonspecific immobilization of DNA complexes (both polymer and lipid vectors) onto serum-coated cell culture polystyrene and self-assembled monolayers of alkanethiols on gold. Also, protocols for the encapsulation of DNA/cationic polymer nanoparticles into hydrogel scaffolds are described, including methods for the encapsulation of low amounts of DNA (<0.2 μg/μL) and high amounts of DNA (>0.2 μg/μL) since incorporation of high amounts of DNA poses significant challenges due to aggregation.

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Formulations and Delivery Limitations of Nucleic‐Acid‐Based Therapies

Segura

2010

Pharmaceutical Sciences Encyclopedia

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Gene delivery has expanded to include the delivery of small interfering RNA (siRNA) and oligonucleotides (ON), which can be used to decrease or downregulate the expression of a target protein. An effective gene delivery system can protect the nucleic acid from degradation, target the appropriate cell population, be efficiently internalized by the cell, avoid degradative pathways, and ultimately localize to the nucleus (DNA) or cytosol. This article focuses on systemic injection formulations, direct injection formulations, matrix‐based delivery, and limitations of nonviral nucleic acid delivery.

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DNA delivery from photocrosslinked PEG hydrogels: encapsulation efficiency, release profiles, and DNA quality

Cited by 129 publications

References 29 publications

Non-viral vector delivery from PEG-hyaluronic acid hydrogels

Non-viral vector delivery from PEG-hyaluronic acid hydrogels

Surface- and Hydrogel-Mediated Delivery of Nucleic Acid Nanoparticles

Formulations and Delivery Limitations of Nucleic‐Acid‐Based Therapies

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