Effect of molecular weight on the transfection efficiency of novel polyurethane as a biodegradable gene vector

Shau, Min‐Da; Tseng, S-Ja; Yang, Tsung-Fu; Cherng, Jong Yuh; Chin, Wei‐Kuo

doi:10.1002/jbm.a.30605

Cited by 32 publications

(10 citation statements)

References 25 publications

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“…Figure 5 shows the relative cell viability of Neuro 2 A cells, 24 h after transfection with the polyplexes prepared at different N/P ratios. Cytotoxicity positively correlated with polymer molecular weight, in good agreement with earlier findings on PEI, PLL and other polymers (8,12,19,31,32). Polyplexes based on the starting polymer showed significant cytotoxicity, similar to polyplexes based on the high molecular weight polymer fractions (ppz950 and ppz570).…”

Section: Resultssupporting

confidence: 91%

Biodegradable Poly(2-Dimethylamino Ethylamino)Phosphazene for In Vivo Gene Delivery to Tumor Cells. Effect of Polymer Molecular Weight

et al. 2007

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Purpose. Previously, we have shown that complexes of plasmid DNA with the biodegradable polymer poly(2-dimethylamino ethylamino)phosphazene (p(DMAEA)-ppz) mediated tumor selective gene expression after intravenous administration in mice. In this study, we investigated the effect of p(DMAEA)-ppz molecular weight on both in vitro and in vivo tumor transfection, as well as on complex induced toxicity. Materials and Methods. p(DMAEA)-ppz with a broad molar mass distribution was fractionated by preparative size exclusion chromatography. Polyplexes consisting of plasmid DNA and the collected polymer fractions were tested for biophysical properties, (cyto)toxicity and transfection activity. Results. Four p(DMAEA)-ppz fractions were collected with weight average molecular weights ranging from 130 to 950 kDa, and with narrow molecular mass distributions (M w /M n from 1.1 to 1.3). At polymer-to-DNA (N/P) ratios above 6, polyplexes based on these polymers were all positively charged (zeta potential 25-29 mV), and had a size of 80-90 nm. The in vitro cytotoxicity of the polyplexes positively correlated with polymer molecular weight. The in vitro transfection activity of the different polyplexes depended on their N/P ratio, and was affected by the degree of cytotoxicity, as well as the colloidal stability of the different polyplexes. Intravenous administration of polyplexes based on the high molecular weight polymers led to apparent toxicity, as a result of polyplex-induced erythrocyte aggregation. On the other hand, administration of polyplexes based on low molecular weight p(DMAEA)-ppz_s (M w 130 kDa) did not show signs of toxicity and resulted in tumor selective gene expression. Conclusion. Polymer molecular weight fractionation enabled us to optimize the transfection efficiency/ toxicity ratio of p(DMAEA)-ppz polyplexes for in vitro and in vivo tumor transfection.

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Section: Resultssupporting

confidence: 91%

Biodegradable Poly(2-Dimethylamino Ethylamino)Phosphazene for In Vivo Gene Delivery to Tumor Cells. Effect of Polymer Molecular Weight

et al. 2007

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“…For example, Shau and coworkers synthesized 2-diethylaminoethylaminepolyurethane (LGEA-PU), consisting of PEG segments and tertiary amines, via step polymerization and post-chemical modification. 125 LGEA-PUs were capable of complexing DNA to form LGEA-PU59/DNA complexes that efficiently transfected COS-7 cells. It was also found that the molecular weight of LGEA-PUs had a significant effect on transfection ability.…”

Section: Polyurethanesmentioning

confidence: 99%

<p>Biodegradable Polymers for Gene-Delivery Applications</p>

Chen

Huang

Law

et al. 2020

IJN

124

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Gene-based therapies have emerged as a new modality for combating a myriad of currently incurable diseases. However, the fragile nature of gene therapeutics has significantly hampered their biomedical applications. Correspondingly, the development of gene-delivery vectors is of critical importance for gene-based therapies. To date, a variety of gene-delivery vectors have been created and utilized for gene delivery. In general, they can be categorized into viral-and non-viral vectors. Due to safety issues associated with viral vectors, non-viral vectors have recently attracted much more research focus. Of these non-viral vectors, polymeric vectors, which have been preferred due to their low immunogenicity, ease of production, controlled chemical composition and high chemical versatility, have constituted an ideal alternative to viral vectors. In particular, biodegradable polymers, which possess advantageous biocompatibility and biosafety, have been considered to have great potential in clinical applications. In this context, the aim of this review is to introduce the recent development and progress of biodegradable polymers for gene delivery applications, especially for their chemical structure design, gene delivery capacity and additional biological functions. Accordingly, we first define and categorize biodegradable polymers, followed by describing their corresponding degradation mechanisms. Various types of biodegradable polymers resulting from natural and synthetic polymers will be introduced and their applications in gene delivery will be examined. Finally, a future perspective regarding the development of biodegradable polymer vectors will be given.

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“…Since the zeta potential of studied complexes is similar (from +16 to +20mV, except the dextran) and only non-specific interaction to the studied cells is discussed, the effect of cell surface charge with the counter-charge complexes is minimal. In a series of polycationic polymers (based on the same framework in structure), the higher molecular weight of a polymer has, the better transfection efficiency would be (40). Results show that the lowest Mw (19 kDa) PDAMA bears the worst transfection but the PEI in a similar Mw (25 kDa) showed the best transfection activities.…”

Section: Correlation Between the Alterations Of Dna Spectra In The Pr...mentioning

confidence: 99%

Investigation of DNA Spectral Conformational Changes and Polymer Buffering Capacity in Relation to Transfection Efficiency of DNA/Polymer Complexes

Cherng

2009

J Pharm Pharm Sci

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Purpose. The relation between transfection efficiency of DNA/polymer complexes and DNA conformational alterations is investigated. The buffering capacity of several synthetic polymers is also studied to relate their performance in transfection efficiency. Methods. The cationic polymer/DNA interaction was evaluated by measuring the alteration of DNA secondary structures in solution before and after the addition of polymer with ATR-FTIR technique. The degree of protonation in aqueous cationic polymers is varied upon pH and different structures. A polymer capable of protonation acts like a proton sponge to react with H+ in titration with HCl. This characteristic was evaluated in relation to transfection efficiency because the capacity would help the release of endocytotic DNA from endosome/lysosome on its way to expression. Results. IR results show that the antisymmetric PO2- vibration of DNA (at 1224 cm-1) shifts toward lower frequencies in complexation with PEI or PLLys (these polymers are able to transfect DNA). By contrast, the antisymmetric PO2- vibration of DNA in presence of PDAMA or dextran (these polymers are poor in DNA transfection) shows a shifting to higher frequencies or no alteration was observed. Interestingly, the polymers with best performance in transfection efficiency are in this order: PEI>PDMAEMA>PLLys>PDAMA>dextran which is in the same order as their polymer buffering capacity. These facts indicate polymers possessing better buffering capacity could result in higher transfection efficiency. Also, we have demonstrated in this paper that the antisymmetric PO2- stretching vibration in IR spectra is sensitive while binding of cationic polymers to DNA. These findings are useful for the development of polymer-based gene delivery systems with better performance in vitro and in vivo

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Effect of molecular weight on the transfection efficiency of novel polyurethane as a biodegradable gene vector

Cited by 32 publications

References 25 publications

Biodegradable Poly(2-Dimethylamino Ethylamino)Phosphazene for In Vivo Gene Delivery to Tumor Cells. Effect of Polymer Molecular Weight

Biodegradable Poly(2-Dimethylamino Ethylamino)Phosphazene for In Vivo Gene Delivery to Tumor Cells. Effect of Polymer Molecular Weight

<p>Biodegradable Polymers for Gene-Delivery Applications</p>

Investigation of DNA Spectral Conformational Changes and Polymer Buffering Capacity in Relation to Transfection Efficiency of DNA/Polymer Complexes

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