In vivo release and gene expression of plasmid DNA by hydrogels of gelatin with different cationization extents

Kubota, Toshihiro; Tomoshige, Ryuji; Fukunaka, Yasunori; Kakemi, Masawo; Tabata, Yasuhiko

doi:10.1016/s0168-3659(03)00197-4

Cited by 105 publications

(91 citation statements)

References 11 publications

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“…For the high MW PLG microspheres, however, the short duration of transgene expression was unexpected given the high MW PLG microspheres released 76% of the entrapped plasmid through 28 days, whereas the low MW PLG release 43% [27]. Note, however, in vitro and in vivo release profiles can differ significantly [24,25]. The shorter transgene expression may result from the interactions with the tissue, as the high MW PLG microspheres were found to aggregate to a greater extent than the low MW PLG.…”

Section: Discussionmentioning

confidence: 99%

“…This observation suggests that sustained release formulations may enhance and prolong transgene expression without requiring multiple interventions. Microspheres and nanospheres injected intramuscularly have demonstrated the capacity of promoting and prolonging transgene expression, though the underlying mechanisms are not well understood [19][20][21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

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Intramuscular delivery of DNA releasing microspheres: Microsphere properties and transgene expression

Jang

Shea²

2006

Journal of Controlled Release

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Plasmid-loaded microspheres can provide localized and sustained release into the target tissue, and thus have the potential to enhance the efficiency of naked DNA at promoting transgene expression. In this report, microsphere design parameters are investigated by correlating the extent and duration of transgene expression intramuscularly to the polymer molecular weight and the mass of DNA delivered. Plasmid DNA was incorporated into poly (lactide-co-glycolide) microspheres using a cryogenic double emulsion process, and microspheres were injected intramuscularly. Bolus injection of naked plasmid was used for control, which exhibited transfection of muscle cells with transgene expression that gradually decreased over time. Microspheres fabricated from low molecular weight polymer had expression levels that increased from day 1 to day 92, which subsequently decreased through day 174. Decreasing the microsphere mass delivered resulted in steady expression during the same time. However, microspheres fabricated with high molecular weight polymer had expression for only 14 days. Intramuscular injection resulted in a foreign body response to the microspheres, and these infiltrating cells adjacent were primarily transfected. This understanding of microsphere properties that determine transgene expression and the distribution of transfected cells may facilitate their application to fields such as tissue engineering or DNA vaccines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intramuscular delivery of DNA releasing microspheres: Microsphere properties and transgene expression

Jang

Shea²

2006

Journal of Controlled Release

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“…Gelatin has been cationized with ethylenediamine to bind DNA within the gel. In vivo release demonstrated greater retention of DNA within the gel, a release rate determined in large part by the water content and extent of crosslinking, and persistence of DNA in the animal for 7-10 days [69,87,88]. Alternatively, DNA complexes, which normally bind non-specifically to collagen, can be modified with a protecting copolymer that reduced interactions between the vector and material and enhanced release [73].…”

Section: Hydrogels-hydrogelsmentioning

confidence: 99%

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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“…30 In previous studies, we have reported that the time period of plasmid DNA release can be regulated only by changing that of cationized gelatin hydrogel degradation, which can be controlled by changing the crosslinking extent for hydrogel preparation. 33,34 In addition, the prolonged time period of gene expression was observed when the gelatin microspheres of slower degradation were used to achieve the longerterm release of plasmid DNA. There was a good correlation in the time period between the plasmid release and gene expression.…”

Section: Suppression Of Tumor Metastasismentioning

confidence: 99%

Suppression of tumor metastasis by NK4 plasmid DNA released from cationized gelatin

et al. 2004

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NK4, composed of the NH 2 -terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts as an HGF-antagonist and angiogenesis inhibitor. This study is an investigation to evaluate the feasibility of controlled release formulation of NK4 plasmid DNA in suppressing the tumor growth, and lung metastasis. Biodegradable cationized gelatin microspheres were prepared for the controlled release of an NK4 plasmid DNA. The cationized gelatin microspheres incorporating NK4 plasmid DNA could continuously release plasmid DNA over 28 days as a result of microspheres degradation following the subcutaneous injection. The injection of cationized gelatin microspheres incorporating NK4 plasmid DNA into the subcutaneous tissue significantly prolonged the survival time period of the mice bearing Lewis lung carcinoma tumor. Increases in the tumor volume and the number of lung metastatic nodules of NK4 plasmid DNA release group were suppressed to a significantly greater extent than that of solution-injected group (77.4 and 64.0%, respectively). The number of blood vessels and the apoptosis cells in the tumor tissue were significantly suppressed (80.4%) and increased (127.3%) against free NK4 plasmid DNA-injected group. Thus, the controlled release of NK4 plasmid DNA augmented angiogenesis suppression and apoptosis of tumor cells, which resulted in suppressed tumor growth. We conclude that this controlled release technology is promising to enhance the tumor suppression achieved by gene expression of NK4.

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In vivo release and gene expression of plasmid DNA by hydrogels of gelatin with different cationization extents

Cited by 105 publications

References 11 publications

Intramuscular delivery of DNA releasing microspheres: Microsphere properties and transgene expression

Intramuscular delivery of DNA releasing microspheres: Microsphere properties and transgene expression

Matrices and scaffolds for DNA delivery in tissue engineering

Suppression of tumor metastasis by NK4 plasmid DNA released from cationized gelatin

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