Robust and prolonged gene expression from injectable polymeric implants

Eliaz, Rom E.; Szoka, Francis C.

doi:10.1038/sj.gt.3301786

Cited by 54 publications

(37 citation statements)

References 22 publications

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“…A thermally induced phase separation [65] was used to create porous DNA loaded scaffolds with a microcellular pore structure that was dependent upon the quenching temperature and duration, solvent/water ratio, and polymer concentration. Finally, an injectable scaffold was developed by dissolving PLG in the plasmid containing biocompatible water-miscible solvent glycofurol [66]. After injection, a solid polymeric implant was formed due to diffusion of the solvent from the site of injection.…”

Section: Scaffold Encapsulationmentioning

confidence: 99%

“…Non-viral vectors delivered from the scaffold can induce localized transgene expression with a duration that may be significantly longer than the duration of vector release [4,66,139]; however, the precise relationship between delivery and duration of expression must be developed. Low dosages of DNA released from a scaffold had shorter durations of expression relative to larger dosages, with modest differences in the expression level [60].…”

Section: Concentration and Durationmentioning

confidence: 99%

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Matrices and scaffolds for DNA delivery in tissue engineering

Laporte¹,

Shea²

2007

Advanced Drug Delivery Reviews

240

208

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Regenerative medicine aims to create functional tissue replacements, typically through creating a controlled environment that promotes and directs the differentiation of stem or progenitor cells, either endogenous or transplanted. Scaffolds serve a central role in many strategies by providing the means to control the local environment. Gene delivery from the scaffold represents a versatile approach to manipulating the local environment for directing cell function. Research at the interface of biomaterials, gene therapy, and drug delivery has identified several design parameters for the vector and the biomaterial scaffold that must be satisfied. Progress has been made towards achieving gene delivery within a tissue engineering scaffold, though the design principles for the materials and vectors that produce efficient delivery require further development. Nevertheless, these advances in obtaining transgene expression with the scaffold have created opportunities to develop greater control of either delivery or expression and to identify the best practices for promoting tissue formation. Strategies to achieve controlled localized expression within the tissue engineering scaffold will have broad application to the regeneration of many tissues, with great promise for clinical therapies.

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Section: Scaffold Encapsulationmentioning

confidence: 99%

Section: Concentration and Durationmentioning

confidence: 99%

Matrices and scaffolds for DNA delivery in tissue engineering

Laporte¹,

Shea²

2007

Advanced Drug Delivery Reviews

240

208

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“…Thermally induced gelling systems show thermoreversible sol/gel transitions and are characterized by a lower critical solution temperature (22)(23)(24)(25). They are liquid at room temperature and produce a gel at and above the lower critical solution temperature (22)(23)(24)(25). The incorporation of cubosomes into a thermoresponsive gel should increase drug loading while, in all probability, yielding a lower, more prolonged drug release compared with pure gel (26).…”

Section: Introductionmentioning

confidence: 99%

“…Such systems have been suggested for the delivery of cells or biopharmaceuticals that are susceptible to heat or organic solvents (21). Thermally induced gelling systems show thermoreversible sol/gel transitions and are characterized by a lower critical solution temperature (22)(23)(24)(25). They are liquid at room temperature and produce a gel at and above the lower critical solution temperature (22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Nanostructured Cubosomes in a Thermoresponsive Depot System: An Alternative Approach for the Controlled Delivery of Docetaxel

et al. 2015

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Abstract. The aim of the present study was to develop and evaluate a thermoresponsive depot system comprising of docetaxel-loaded cubosomes. The cubosomes were dispersed within a thermoreversible gelling system for controlled drug delivery. The cubosome dispersion was prepared by dilution method, followed by homogenization using glyceryl monooleate, ethanol and Pluronic ® F127 in distilled water. The cubosome dispersion was then incorporated into a gelling system prepared with Pluronic ® F127 and Pluronic ® F68 in various ratios to formulate a thermoresponsive depot system. The thermoresponsive depot formulations undergo a thermoreversible gelation process i.e., they exists as free flowing liquids at room temperature, and transforms into gels at higher temperatures e.g., body temperature, to form a stable depot in aqueous environment. The mean particle size of the cubosomes in the dispersion prepared with Pluronic ® F127, with and without the drug was found to be 170 and 280 nm, respectively. The prepared thermoresponsive depot system was evaluated by assessing various parameters like time for gelation, injectability, gel erosion, and in-vitro drug release. The drug-release studies of the cubosome dispersion before incorporation into the gelling system revealed that a majority (∼97%) of the drug was released within 12 h. This formulation also showed a short lag time (∼3 min). However, when incorporated into a thermoresponsive depot system, the formulation exhibited an initial burst release of ∼21%, and released only ∼39% drug over a period of 12 h, thus indicating its potential as a controlled drug delivery system.

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“…Direct injection of the plasmid showed no significant enhancement of local tissue formation. In a different study an injectable implant solution was made by mixing plasmid DNA in water with PLGA in glycofurol (Eliaz & Szoka 2002). The ability of the released plasmid to transfect cells in mice was assessed using three independent plasmids.…”

Section: −2mentioning

confidence: 99%

Gene therapy used for tissue engineering applications

Heyde

Partridge

Oreffo

et al. 2007

Journal of Pharmacy and Pharmacology

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This review highlights the advances at the interface between tissue engineering and gene therapy. There are a large number of reports on gene therapy in tissue engineering, and these cover a huge range of different engineered tissues, different vectors, scaffolds and methodology. The review considers separately in-vitro and in-vivo gene transfer methods. The in-vivo gene transfer method is described first, using either viral or non-viral vectors to repair various tissues with and without the use of scaffolds. The use of a scaffold can overcome some of the challenges associated with delivery by direct injection. The ex-vivo method is described in the second half of the review. Attempts have been made to use this therapy for bone, cartilage, wound, urothelial, nerve tissue regeneration and for treating diabetes using viral or non-viral vectors. Again porous polymers can be used as scaffolds for cell transplantation. There are as yet few comparisons between these many different variables to show which is the best for any particular application. With few exceptions, all of the results were positive in showing some gene expression and some consequent effect on tissue growth and remodelling. Some of the principal advantages and disadvantages of various methods are discussed.

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Robust and prolonged gene expression from injectable polymeric implants

Abstract: We introduce an injectable system for the formation of a biodegradable DNA-containing

Cited by 54 publications

References 22 publications

Matrices and scaffolds for DNA delivery in tissue engineering

Matrices and scaffolds for DNA delivery in tissue engineering

Nanostructured Cubosomes in a Thermoresponsive Depot System: An Alternative Approach for the Controlled Delivery of Docetaxel

Gene therapy used for tissue engineering applications

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