Local release of siRNA using polyplex-loaded thermosensitive hydrogels

Fliervoet, Lies A. L.; Zhang, Heyang; Groesen, Emma van; Fortuin, Kyra; Duin, Naut J. C. B.; Remaut, Katrien; Schiffelers, Raymond M.; Hennink, Wim E.; Vermonden, Tina

doi:10.1039/d0nr03147j

Cited by 28 publications

(44 citation statements)

References 52 publications

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“…During the recent decades, intelligent hydrogels have been investigated extensively [1][2][3][4] and widely applied in biomedicine. [5][6][7][8][9][10][11][12] While many efforts have been made to prepare various hydrogels as sustained release carriers of drugs, [13][14][15][16][17][18][19] little is known about the unique role of any intelligent hydrogel in a transdermal formulation for local photodynamic therapy (PDT) of a skin disease, where a sustained release is, however, usually not required.…”

Section: Introductionmentioning

confidence: 99%

An Intelligent Transdermal Formulation of ALA‐Loaded Copolymer Thermogel with Spontaneous Asymmetry by Using Temperature‐Induced Sol–Gel Transition and Gel–Sol (Suspension) Transition on Different Sides

Cao

Chen

Cao³

et al. 2021

Adv Funct Materials

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Aqueous solutions of some amphiphilic block copolymers undergo a sol-gel transition upon heating and are thus called thermogels. In the thermogel family, some systems also exhibit a gel-sol (suspension) transition at higher temperatures following the sol-gel transition, which is usually ignored in biomedical applications. Herein, for the first time, a case is reported employing both the sol-gel transition and the gel-sol (suspension) transition, which is found in the development of a transdermal hydrogel formulation containing 5-aminolevulinic acid for photodynamic therapy (PDT) of skin disease. Two poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-coglycolide) triblock copolymers of different block lengths are synthesized. The transition temperatures of the formulation can be easily adjusted to meet the condition of sol-gel transition temperature (T gel ) < room temperature (T air ) < gel-sol (suspension) temperature (T sol (suspension) ) < body temperature (T body ) via changing the blending ratio. Therefore, after applying to skin, formulation of spontaneous asymmetry with a hydrogel outside and a sol (suspension) inside can avoid free flowing and achieve rapid release to ensure an efficient PDT. This study demonstrates such a concept via characterizations of the "block blend" biomaterials and drug release profiles, and also via cell experiments, in vitro permeation, and in vivo transdermal delivery studies.

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Section: Introductionmentioning

confidence: 99%

An Intelligent Transdermal Formulation of ALA‐Loaded Copolymer Thermogel with Spontaneous Asymmetry by Using Temperature‐Induced Sol–Gel Transition and Gel–Sol (Suspension) Transition on Different Sides

Cao

Chen

Cao³

et al. 2021

Adv Funct Materials

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“…This approach is most often adopted for hydrogels, where the RNA complexes are mixed into the polymer solution before cross-linking the gel. So far, most studies investigated hydrogels made of natural [ 49 , 97 , 98 ] or synthetic [ 62 , 64 , [99] , [100] , [101] , [102] ] polymers or a mixture thereof [ [103] , [104] , [105] , [106] ], but RNA complexes have also been successfully mixed into inorganic HA cements [ 107 ]. Compared to diffusional post-loading, where the complexes are loosely associated with the material, this method usually leads to stronger retention of RNA complexes and thus to release kinetics that depend on degradation of the polymer matrix.…”

Section: Modulating Rna Delivery From Biomaterialsmentioning

confidence: 99%

“…Fliervoet et al. [ 101 ] used triblock polymers of b-poly(N-isopropylacrylamide) (PNIPAM), polyethyleneglycol (PEG) and poly(2-26 dimethylaminoethyl methacrylate) (PDMAEMA) to produce thermosensitive siRNA polyplexes (PNIPAM-PEG-PDMAEMA) and a thermosensitive hydrogel (PNIPAM-PEG-PNIPAM). Although they successfully demonstrated thermosensitive behavior of both the polyplexes upon heating from 10°C to 37°C, the benefit of such a system may be questionable in view of the constant body temperature.…”

Section: Modulating Rna Delivery From Biomaterialsmentioning

confidence: 99%

Designing biomaterials for the delivery of RNA therapeutics to stimulate bone healing

Andrée

Yang

Brock

et al. 2021

Materials Today Bio

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Ribonucleic acids (small interfering RNA, microRNA, and messenger RNA) have been emerging as a promising new class of therapeutics for bone regeneration. So far, however, research has mostly focused on stability and complexation of these oligonucleotides for systemic delivery. By comparison, delivery of RNA nanocomplexes from biomaterial carriers can facilitate a spatiotemporally controlled local delivery of osteogenic oligonucleotides. This review provides an overview of the state-of-the-art in the design of biomaterials which allow for temporal and spatial control over RNA delivery. We correlate this concept of spatiotemporally controlled RNA delivery to the most relevant events that govern bone regeneration to evaluate to which extent tuning of release kinetics is required. In addition, inspired by the physiological principles of bone regeneration, potential new RNA targets are presented. Finally, considerations for clinical translation and upscaled production are summarized to stimulate the design of clinically relevant RNA-releasing biomaterials.

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“…In-situ -forming injectable hydrogels as implantable biomaterials/devices have attracted tremendous attention because of their minimally invasive administration mode [ [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ]. In particular, thermosensitive and biodegradable hydrogels comprised of copolymers of hydrophobic polyesters, such as poly(lactic acid) (PLA), poly( ε -caprolactone) (PCL), poly(lactic acid- co -glycolic acid) (PLGA), poly( ε -caprolactone- co -glycolic acid) (PCGA), poly( ε -caprolactone- co -lactic acid) (PCLA), and hydrophilic poly(ethylene glycol) (PEG) are free-flowing polymer aqueous solutions at low or ambient temperature; however, they exhibit sol-gel transitions in response to the changes in temperature [ [31] , [32] , [33] , [34] , [35] , [36] ].…”

Section: Introductionmentioning

confidence: 99%

Injectable and thermosensitive hydrogels mediating a universal macromolecular contrast agent with radiopacity for noninvasive imaging of deep tissues

Wang

Chen

et al. 2021

Bioactive Materials

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It is very challenging to visualize implantable medical devices made of biodegradable polymers in deep tissues. Herein, we designed a novel macromolecular contrast agent with ultrahigh radiopacity (iodinate content > 50%) via polymerizing an iodinated trimethylene carbonate monomer into the two ends of poly(ethylene glycol) (PEG). A set of thermosensitive and biodegradable polyester-PEG-polyester triblock copolymers with varied polyester compositions synthesized by us, which were soluble in water at room temperature and could spontaneously form hydrogels at body temperature, were selected as the demonstration materials. The addition of macromolecular contrast agent did not obviously compromise the injectability and thermogelation properties of polymeric hydrogels, but conferred them with excellent X-ray opacity, enabling visualization of the hydrogels at clinically relevant depths through X-ray fluoroscopy or Micro-CT. In a mouse model, the 3D morphology of the radiopaque hydrogels after injection into different target sites was visible using Micro-CT imaging, and their injection volume could be accurately obtained. Furthermore, the subcutaneous degradation process of a radiopaque hydrogel could be non-invasively monitored in a real-time and quantitative manner. In particular, the corrected degradation curve based on Micro-CT imaging well matched with the degradation profile of virgin polymer hydrogel determined by the gravimetric method. These findings indicate that the macromolecular contrast agent has good universality for the construction of various radiopaque polymer hydrogels, and can nondestructively trace and quantify their degradation in vivo . Meanwhile, the present methodology developed by us affords a platform technology for deep tissue imaging of polymeric materials.

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Local release of siRNA using polyplex-loaded thermosensitive hydrogels

Abstract: An injectable thermosensitive hydrogel to promote local and sustained release of small nanosized (10–20 nm) siRNA polyplexes.

Cited by 28 publications

References 52 publications

An Intelligent Transdermal Formulation of ALA‐Loaded Copolymer Thermogel with Spontaneous Asymmetry by Using Temperature‐Induced Sol–Gel Transition and Gel–Sol (Suspension) Transition on Different Sides

An Intelligent Transdermal Formulation of ALA‐Loaded Copolymer Thermogel with Spontaneous Asymmetry by Using Temperature‐Induced Sol–Gel Transition and Gel–Sol (Suspension) Transition on Different Sides

Designing biomaterials for the delivery of RNA therapeutics to stimulate bone healing

Injectable and thermosensitive hydrogels mediating a universal macromolecular contrast agent with radiopacity for noninvasive imaging of deep tissues

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