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Nanomembrane-driven co-elution and integration of active chemotherapeutic and anti-inflammatory agents.

Pierstorff E, Ho D - Int J Nanomedicine (2008)

Bottom Line: Confirmation of drug release and functionality was demonstrated via suppression of the interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) inflammatory cytokines (Dex), as well as TUNEL staining and DNA fragmentation analysis (Dox).The inherent biocompatibility of the copolymeric material is further demonstrated by the lack of inflammation and apoptosis induction in cells grown on the copolymer films.Thus a layer-by-layer anchored deposition of an anti-inflammatory and chemotherapeutic functionalized copolymer film is able to localize drug dosage to the surface of a medical device, all with an innate material thickness of 4 nm per layer.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Robert R McCormick School of Engineering and Applied Science, Feinberg School of Medicine, Northwestern University, Evanston, IL, USA. e-pierstorff@northwestern.edu

ABSTRACT
The release of therapeutic drugs from the surface of implantable devices is instrumental for the reduction of medical costs and toxicity associated with systemic administration. In this study we demonstrate the triblock copolymer-mediated deposition and release of multiple therapeutics from a single thin film at the air-water interface via Langmuir-Blodgett deposition. The dual drug elution of dexamethasone (Dex) and doxorubicin hydrochloride (Dox) from the thin film is measured by response in the RAW 264.7 murine macrophage cell line. The integrated hydrophilic and hydrophobic components of the polymer structure allows for the creation of hybrids of the copolymer and the hydrophobic Dex and the hydrophilic Dox. Confirmation of drug release and functionality was demonstrated via suppression of the interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) inflammatory cytokines (Dex), as well as TUNEL staining and DNA fragmentation analysis (Dox). The inherent biocompatibility of the copolymeric material is further demonstrated by the lack of inflammation and apoptosis induction in cells grown on the copolymer films. Thus a layer-by-layer anchored deposition of an anti-inflammatory and chemotherapeutic functionalized copolymer film is able to localize drug dosage to the surface of a medical device, all with an innate material thickness of 4 nm per layer.

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A) RT-PCR analysis of IL-6 gene expression was done following macrophage incubation with the polymer–Dex–Dox nanofilms. Gene expression assays with aqueous Dex added were conducted as a control for Dex activity. Results indicated the incorporation of Dex into the copolymer–Dex–Dox thin film and a potent drug releasing activity as shown through a substantial reduction in inflammatory gene expression. B) In addition, RT-PCR analysis of TNFα gene expression was done following macrophage incubation with the polymer–Dex–Dox nanofilms. Gene expression assays with aqueous Dex added were conducted as a control for Dex activity. Results further indicated the incorporation of Dex into the copolymer–Dex–Dox thin film and a potent drug releasing activity as shown through a substantial reduction in inflammatory gene expression. The broad suppression of inflammatory gene expression demonstrates an efficient hybrid nanofilm system for an active drug delivery interface. Data was acquired and responses were observed from a minimum of three trials.
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f3-ijn-3-425: A) RT-PCR analysis of IL-6 gene expression was done following macrophage incubation with the polymer–Dex–Dox nanofilms. Gene expression assays with aqueous Dex added were conducted as a control for Dex activity. Results indicated the incorporation of Dex into the copolymer–Dex–Dox thin film and a potent drug releasing activity as shown through a substantial reduction in inflammatory gene expression. B) In addition, RT-PCR analysis of TNFα gene expression was done following macrophage incubation with the polymer–Dex–Dox nanofilms. Gene expression assays with aqueous Dex added were conducted as a control for Dex activity. Results further indicated the incorporation of Dex into the copolymer–Dex–Dox thin film and a potent drug releasing activity as shown through a substantial reduction in inflammatory gene expression. The broad suppression of inflammatory gene expression demonstrates an efficient hybrid nanofilm system for an active drug delivery interface. Data was acquired and responses were observed from a minimum of three trials.

Mentions: Dex incorporation and release from the deposited polymer–Dex–Dox thin films was monitored via the inflammation of cells grown on the polymer–Dex–Dox films with LPS followed by quantitative RT-PCR trials to examine the Dex-mediated suppression of IL-6 and TNFα expression (Figures 3A and 3B). IL-6 gene expression was significantly lower in cells grown on polymer–Dex–Dox films, suggesting that the drug was both present in the film and accessible to the cells frown on the slide (Figure 3A). As a control for Dex mediated cellular inflammation suppression, aqueous Dex was added directly to the media of cells inflamed with LPS. The reduction in IL-6 expression was comparable in cells grown on the polymer–Dex–Dox films (Figure 3A). Furthermore, the TNFα locus was used as an additional demonstration of inflammation reduction in cells grown on polymer–Dex–Dox. As with IL-6, there was significant and comparable reduction of TNFα expression in cells grown on the polymer–Dex–Dox films (Figure 3B).


Nanomembrane-driven co-elution and integration of active chemotherapeutic and anti-inflammatory agents.

Pierstorff E, Ho D - Int J Nanomedicine (2008)

A) RT-PCR analysis of IL-6 gene expression was done following macrophage incubation with the polymer–Dex–Dox nanofilms. Gene expression assays with aqueous Dex added were conducted as a control for Dex activity. Results indicated the incorporation of Dex into the copolymer–Dex–Dox thin film and a potent drug releasing activity as shown through a substantial reduction in inflammatory gene expression. B) In addition, RT-PCR analysis of TNFα gene expression was done following macrophage incubation with the polymer–Dex–Dox nanofilms. Gene expression assays with aqueous Dex added were conducted as a control for Dex activity. Results further indicated the incorporation of Dex into the copolymer–Dex–Dox thin film and a potent drug releasing activity as shown through a substantial reduction in inflammatory gene expression. The broad suppression of inflammatory gene expression demonstrates an efficient hybrid nanofilm system for an active drug delivery interface. Data was acquired and responses were observed from a minimum of three trials.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2636579&req=5

f3-ijn-3-425: A) RT-PCR analysis of IL-6 gene expression was done following macrophage incubation with the polymer–Dex–Dox nanofilms. Gene expression assays with aqueous Dex added were conducted as a control for Dex activity. Results indicated the incorporation of Dex into the copolymer–Dex–Dox thin film and a potent drug releasing activity as shown through a substantial reduction in inflammatory gene expression. B) In addition, RT-PCR analysis of TNFα gene expression was done following macrophage incubation with the polymer–Dex–Dox nanofilms. Gene expression assays with aqueous Dex added were conducted as a control for Dex activity. Results further indicated the incorporation of Dex into the copolymer–Dex–Dox thin film and a potent drug releasing activity as shown through a substantial reduction in inflammatory gene expression. The broad suppression of inflammatory gene expression demonstrates an efficient hybrid nanofilm system for an active drug delivery interface. Data was acquired and responses were observed from a minimum of three trials.
Mentions: Dex incorporation and release from the deposited polymer–Dex–Dox thin films was monitored via the inflammation of cells grown on the polymer–Dex–Dox films with LPS followed by quantitative RT-PCR trials to examine the Dex-mediated suppression of IL-6 and TNFα expression (Figures 3A and 3B). IL-6 gene expression was significantly lower in cells grown on polymer–Dex–Dox films, suggesting that the drug was both present in the film and accessible to the cells frown on the slide (Figure 3A). As a control for Dex mediated cellular inflammation suppression, aqueous Dex was added directly to the media of cells inflamed with LPS. The reduction in IL-6 expression was comparable in cells grown on the polymer–Dex–Dox films (Figure 3A). Furthermore, the TNFα locus was used as an additional demonstration of inflammation reduction in cells grown on polymer–Dex–Dox. As with IL-6, there was significant and comparable reduction of TNFα expression in cells grown on the polymer–Dex–Dox films (Figure 3B).

Bottom Line: Confirmation of drug release and functionality was demonstrated via suppression of the interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) inflammatory cytokines (Dex), as well as TUNEL staining and DNA fragmentation analysis (Dox).The inherent biocompatibility of the copolymeric material is further demonstrated by the lack of inflammation and apoptosis induction in cells grown on the copolymer films.Thus a layer-by-layer anchored deposition of an anti-inflammatory and chemotherapeutic functionalized copolymer film is able to localize drug dosage to the surface of a medical device, all with an innate material thickness of 4 nm per layer.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Robert R McCormick School of Engineering and Applied Science, Feinberg School of Medicine, Northwestern University, Evanston, IL, USA. e-pierstorff@northwestern.edu

ABSTRACT
The release of therapeutic drugs from the surface of implantable devices is instrumental for the reduction of medical costs and toxicity associated with systemic administration. In this study we demonstrate the triblock copolymer-mediated deposition and release of multiple therapeutics from a single thin film at the air-water interface via Langmuir-Blodgett deposition. The dual drug elution of dexamethasone (Dex) and doxorubicin hydrochloride (Dox) from the thin film is measured by response in the RAW 264.7 murine macrophage cell line. The integrated hydrophilic and hydrophobic components of the polymer structure allows for the creation of hybrids of the copolymer and the hydrophobic Dex and the hydrophilic Dox. Confirmation of drug release and functionality was demonstrated via suppression of the interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) inflammatory cytokines (Dex), as well as TUNEL staining and DNA fragmentation analysis (Dox). The inherent biocompatibility of the copolymeric material is further demonstrated by the lack of inflammation and apoptosis induction in cells grown on the copolymer films. Thus a layer-by-layer anchored deposition of an anti-inflammatory and chemotherapeutic functionalized copolymer film is able to localize drug dosage to the surface of a medical device, all with an innate material thickness of 4 nm per layer.

Show MeSH
Related in: MedlinePlus