Polymers and hydrogels for local nucleic acid delivery

Fliervoet, Lies A. L.; Engbersen, Johan F.J.; Schiffelers, Raymond M.; Hennink, Wim E.; Vermonden, Tina

doi:10.1039/c8tb01795f

Cited by 32 publications

(30 citation statements)

References 175 publications

(226 reference statements)

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“…1 D, where the storage modulus of Alg-PDRN sharply increased compared with that of Alg at Alg concentrations of 4% and 5%. This phenomenon can be explained by the strengthening of the hydrogel by the presence of PDRN, which acted as a semi-interpenetrating polymer network 35 . The homogeneous dispersion of PDRN led to an increased stress transfer from polymer chains to PDRN, similar to the effect of nano fillers such as carbon nanotubes, cellulose nano crystals, and nano clay 36 .…”

Section: Resultsmentioning

confidence: 99%

Polydeoxyribonucleotide-delivering therapeutic hydrogel for diabetic wound healing

Shin

Park

Choi

et al. 2020

Sci Rep

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Patients with diabetes experience delayed wound healing because of the uncontrolled glucose level in their bloodstream, which leads to impaired function of white blood cells, poor circulation, decreased production and repair of new blood vessels. Treatment using polydeoxyribonucleotide (PDRN), which is a DNA extracted from the sperm cells of salmon, has been introduced to accelerate the healing process of diabetic wounds. To accelerate the wound-healing process, sustained delivery of PDRN is critical. In this study, taking advantage of the non-invasive gelation property of alginate, PDRN was loaded inside the hydrogel (Alg-PDRN). The release behavior of PDRN was altered by controlling the crosslinking density of the Alg hydrogel. The amount of PDRN was the greatest inside the hydrogel with the highest crosslinking density because of the decreased diffusion. However, there was an optimal degree of crosslinking for the effective release of PDRN. In vitro studies using human dermal fibroblasts and diabetes mellitus fibroblasts and an in ovo chorioallantoic membrane assay confirmed that the Alg-PDRN hydrogel effectively induced cell proliferation and expression of angiogenic growth factors and promoted new blood vessel formation. Its effectiveness for accelerated diabetic wound healing was also confirmed in an in-vivo animal experiment using a diabetic mouse model.

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Section: Resultsmentioning

confidence: 99%

Polydeoxyribonucleotide-delivering therapeutic hydrogel for diabetic wound healing

Shin

Park

Choi

et al. 2020

Sci Rep

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“…Hydrogels are water-swollen cross-linked networks of hydrophilic polymers, which have been used for the delivery of various biomolecules, including siRNA. [14][15][16][17] The nucleic acids are entrapped within the hydrogel either as siRNA conjugates or loaded in nanoparticles, and the release kinetics can be tuned by varying hydrogel properties such as polymer concentration and cross-link density. 17,18 In this way, hydrogels assist in local retention and sustained release of siRNA to enhance in vivo efficacy and at the same time limit off-target toxicity.…”

Section: Introductionmentioning

confidence: 99%

“…[14][15][16][17] The nucleic acids are entrapped within the hydrogel either as siRNA conjugates or loaded in nanoparticles, and the release kinetics can be tuned by varying hydrogel properties such as polymer concentration and cross-link density. 17,18 In this way, hydrogels assist in local retention and sustained release of siRNA to enhance in vivo efficacy and at the same time limit off-target toxicity. 18 While many hydrogels have been investigated for local release of therapeutics, injectable formulations are preferred over preformed hydrogels, since in situ gelation can take place under physiological conditions upon injection without the need of an invasive surgical intervention.…”

Section: Introductionmentioning

confidence: 99%

“…[19][20][21] Especially the use of stimuli-responsive polymers gained a lot of interest, as they can respond to external environmental triggers, like temperature, pH or light exposure. 17 Temperature-sensitive hydrogels are one of the most studied class of stimuli-responsive polymer systems, and the self-assembly of these polymers occurs at a critical temperature, the so-called cloud point (CP) in aqueous solution. Because poly(N-isopropylacrylamide) (PNIPAM)-based polymers have a CP around 32°C, they are very attractive materials for biomedical and pharmaceutical applications.…”

Section: Introductionmentioning

confidence: 99%

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Local release of siRNA using polyplex-loaded thermosensitive hydrogels

et al. 2020

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“…Three-dimensional (3D) printing is a promising technique for fabricating implantable hydrogels for various biomedical applications [24,[26][27][28][29]. These types of hydrogels have been reported in the literature as a potential scaffold for post-surgery applications in in vivo experiments [30,31]. However, there are just few numbers of these printable scaffolds, like poly-lactic acid (PLA) hydrogels, which are approved by FDA.…”

Section: Implantable Hydrogelsmentioning

confidence: 99%

Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

Askari

Seyfoori

Amereh

et al. 2020

Gels

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Currently, surgical operations, followed by systemic drug delivery, are the prevailing treatment modality for most diseases, including cancers and trauma-based injuries. Although effective to some extent, the side effects of surgery include inflammation, pain, a lower rate of tissue regeneration, disease recurrence, and the non-specific toxicity of chemotherapies, which remain significant clinical challenges. The localized delivery of therapeutics has recently emerged as an alternative to systemic therapy, which not only allows the delivery of higher doses of therapeutic agents to the surgical site, but also enables overcoming post-surgical complications, such as infections, inflammations, and pain. Due to the limitations of the current drug delivery systems, and an increasing clinical need for disease-specific drug release systems, hydrogels have attracted considerable interest, due to their unique properties, including a high capacity for drug loading, as well as a sustained release profile. Hydrogels can be used as local drug performance carriers as a means for diminishing the side effects of current systemic drug delivery methods and are suitable for the majority of surgery-based injuries. This work summarizes recent advances in hydrogel-based drug delivery systems (DDSs), including formulations such as implantable, injectable, and sprayable hydrogels, with a particular emphasis on stimuli-responsive materials. Moreover, clinical applications and future opportunities for this type of post-surgery treatment are also highlighted.

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Polymers and hydrogels for local nucleic acid delivery

Abstract: This review focusses on the rational design of materials (from polymers to hydrogel materials) to achieve successful local delivery of therapeutic nucleic acids.

Cited by 32 publications

References 175 publications

Polydeoxyribonucleotide-delivering therapeutic hydrogel for diabetic wound healing

Polydeoxyribonucleotide-delivering therapeutic hydrogel for diabetic wound healing

Local release of siRNA using polyplex-loaded thermosensitive hydrogels

Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

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