The effect of formulation parameters on the size of poly((2-dimethylamino)ethyl methacrylate)-plasmid complexes
Identifieur interne : 002592 ( Main/Exploration ); précédent : 002591; suivant : 002593The effect of formulation parameters on the size of poly((2-dimethylamino)ethyl methacrylate)-plasmid complexes
Auteurs : J.-Y Cherng [Pays-Bas] ; H. Talsma [Pays-Bas] ; R. Verrijk [Pays-Bas] ; D. J. A Crommelin [Pays-Bas] ; W. E Hennink [Pays-Bas]Source :
- European Journal of Pharmaceutics and Biopharmaceutics [ 0939-6411 ] ; 1999.
English descriptors
- Teeft :
- Acetate buffer, Aggregation, Aqueous solution, Aqueous solutions, Biopharmaceutics, Cationic, Cell viability, Cherng, Colloidal systems, Crommelin, Dimensional surface plot, Dynamic light, European journal, Experimental design, Experimental designs, Formulation parameters, Good agreement, Hepes, High concentration, High plasmid concentration, Higher plasmid concentration, Independent variables, Ionic strength, Marginal effect, Molecular weight, Nacl, Optimization, Optimization design, Particle size, Pdmaema, Pharm, Pharmaceutics, Plasmid, Plasmid concentration, Plasmid ratio, Polymer, Polymer concentration, Polyplexes, Relative transfection, Rpmi, Screening design, Small particles, Small polyplexes, Standard deviation, Sucrose, Transfection, Tween.
Abstract
Abstract: The aim of this study was to gain insight into the formulation parameters affecting the size of poly((2-dimethylamino)ethyl methacrylate)-plasmid complexes (polyplexes). Experimental designs were applied to screen and optimize several variables, which may influence the complex size. In a screening design, it was demonstrated that at a fixed concentration of plasmid (40 μg/ml) after incubation with polymer, the size of the resulting polyplexes was highly dependent on the polymer/plasmid ratio as well as on the pH, viscosity (i.e. sucrose concentration) and ionic strength of the aqueous solution. However, the temperature, PEG 600 (up to 5% (v/v)) and Tween 80 (up to 0.2%) had a marginal effect on the size of the polyplexes. In an optimization design, the effect of the pH, polymer/plasmid ratio and Tween on the size of the polymer/plasmid complexes prepared at relatively high concentration of plasmid (50–200 μg/ml) was evaluated. Based on the results of the optimization design, a mathematical model was derived, which describes the relationship between the size of the polyplexes and the different formulation parameters. This model shows that even at high plasmid concentration (200 μg/ml), small sized polyplexes were formed at low pH and ionic strength, especially when the solution contains 20% (w/v) sucrose. This concentrated polyplex dispersion (polymer/plasmid ratio >3/1 (w/w), 200 μg plasmid/ml) can be diluted down to 5 μg/ml plasmid without significant changes in particle size and transfection potential. At lower ratios, a growth in particle size was observed upon dilution of the complexes, which might also explain the low transfection efficiency of these polyplexes in vitro.
Url:
DOI: 10.1016/S0939-6411(98)00103-9
Affiliations:
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Talsma</name><affiliation wicri:level="4"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pharmaceutics, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Verrijk, R" sort="Verrijk, R" uniqKey="Verrijk R" first="R" last="Verrijk">R. Verrijk</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>OctoPlus B.V., Niels Bohrweg, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Crommelin, D J A" sort="Crommelin, D J A" uniqKey="Crommelin D" first="D. J. A" last="Crommelin">D. J. A Crommelin</name><affiliation wicri:level="4"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pharmaceutics, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Hennink, W E" sort="Hennink, W E" uniqKey="Hennink W" first="W. E" last="Hennink">W. E Hennink</name><affiliation wicri:level="4"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pharmaceutics, Utrecht University, Utrecht</wicri:regionArea><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation><affiliation wicri:level="4"><country wicri:rule="url">Pays-Bas</country><wicri:regionArea>Corresponding author. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80.082, 3508 TB Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">European Journal of Pharmaceutics and Biopharmaceutics</title><title level="j" type="abbrev">EJPB</title><idno type="ISSN">0939-6411</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999">1999</date><biblScope unit="volume">47</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="215">215</biblScope><biblScope unit="page" to="224">224</biblScope></imprint><idno type="ISSN">0939-6411</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0939-6411</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Acetate buffer</term><term>Aggregation</term><term>Aqueous solution</term><term>Aqueous solutions</term><term>Biopharmaceutics</term><term>Cationic</term><term>Cell viability</term><term>Cherng</term><term>Colloidal systems</term><term>Crommelin</term><term>Dimensional surface plot</term><term>Dynamic light</term><term>European journal</term><term>Experimental design</term><term>Experimental designs</term><term>Formulation parameters</term><term>Good agreement</term><term>Hepes</term><term>High concentration</term><term>High plasmid concentration</term><term>Higher plasmid concentration</term><term>Independent variables</term><term>Ionic strength</term><term>Marginal effect</term><term>Molecular weight</term><term>Nacl</term><term>Optimization</term><term>Optimization design</term><term>Particle size</term><term>Pdmaema</term><term>Pharm</term><term>Pharmaceutics</term><term>Plasmid</term><term>Plasmid concentration</term><term>Plasmid ratio</term><term>Polymer</term><term>Polymer concentration</term><term>Polyplexes</term><term>Relative transfection</term><term>Rpmi</term><term>Screening design</term><term>Small particles</term><term>Small polyplexes</term><term>Standard deviation</term><term>Sucrose</term><term>Transfection</term><term>Tween</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The aim of this study was to gain insight into the formulation parameters affecting the size of poly((2-dimethylamino)ethyl methacrylate)-plasmid complexes (polyplexes). Experimental designs were applied to screen and optimize several variables, which may influence the complex size. In a screening design, it was demonstrated that at a fixed concentration of plasmid (40 μg/ml) after incubation with polymer, the size of the resulting polyplexes was highly dependent on the polymer/plasmid ratio as well as on the pH, viscosity (i.e. sucrose concentration) and ionic strength of the aqueous solution. However, the temperature, PEG 600 (up to 5% (v/v)) and Tween 80 (up to 0.2%) had a marginal effect on the size of the polyplexes. In an optimization design, the effect of the pH, polymer/plasmid ratio and Tween on the size of the polymer/plasmid complexes prepared at relatively high concentration of plasmid (50–200 μg/ml) was evaluated. Based on the results of the optimization design, a mathematical model was derived, which describes the relationship between the size of the polyplexes and the different formulation parameters. This model shows that even at high plasmid concentration (200 μg/ml), small sized polyplexes were formed at low pH and ionic strength, especially when the solution contains 20% (w/v) sucrose. This concentrated polyplex dispersion (polymer/plasmid ratio >3/1 (w/w), 200 μg plasmid/ml) can be diluted down to 5 μg/ml plasmid without significant changes in particle size and transfection potential. At lower ratios, a growth in particle size was observed upon dilution of the complexes, which might also explain the low transfection efficiency of these polyplexes in vitro.</div></front></TEI><affiliations><list><country><li>Pays-Bas</li></country><region><li>Hollande-Méridionale</li><li>Utrecht (province)</li></region><settlement><li>Leyde</li><li>Utrecht</li></settlement><orgName><li>Université d'Utrecht</li></orgName></list><tree><country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Cherng, J Y" sort="Cherng, J Y" uniqKey="Cherng J" first="J.-Y" last="Cherng">J.-Y Cherng</name></region><name sortKey="Crommelin, D J A" sort="Crommelin, D J A" uniqKey="Crommelin D" first="D. J. A" last="Crommelin">D. J. A Crommelin</name><name sortKey="Hennink, W E" sort="Hennink, W E" uniqKey="Hennink W" first="W. E" last="Hennink">W. E Hennink</name><name sortKey="Hennink, W E" sort="Hennink, W E" uniqKey="Hennink W" first="W. E" last="Hennink">W. E Hennink</name><name sortKey="Talsma, H" sort="Talsma, H" uniqKey="Talsma H" first="H" last="Talsma">H. Talsma</name><name sortKey="Verrijk, R" sort="Verrijk, R" uniqKey="Verrijk R" first="R" last="Verrijk">R. Verrijk</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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