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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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Related in: MedlinePlus

Microscopy Dox impact upon cellular proliferation and morphology was demonstrated via confocal microscopy. Macrophages cultured atop glass or polymer only substrates produced highly confluent growth. Macrophages cultured atop polymer–Dox and polymer–Dex–Dox nanofilm hybrids generated decrease cell confluency, enlarged, preapoptotic cells, as well as shrunken apoptotic cells due to Dox-induced cell death/apoptosis. TUNEL assays demonstrate the progression of cells grown on polymer–Dox and polymer–Dex–Dox nanofilm hybrids to apoptosis.Notes: Magnification: 40X, Leica inverted microscope Confocal Laser Scanning System.
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f5-ijn-3-425: Microscopy Dox impact upon cellular proliferation and morphology was demonstrated via confocal microscopy. Macrophages cultured atop glass or polymer only substrates produced highly confluent growth. Macrophages cultured atop polymer–Dox and polymer–Dex–Dox nanofilm hybrids generated decrease cell confluency, enlarged, preapoptotic cells, as well as shrunken apoptotic cells due to Dox-induced cell death/apoptosis. TUNEL assays demonstrate the progression of cells grown on polymer–Dox and polymer–Dex–Dox nanofilm hybrids to apoptosis.Notes: Magnification: 40X, Leica inverted microscope Confocal Laser Scanning System.

Mentions: Confocal microscopy also revealed the impact of Dox elution from the copolymeric nanofilm upon cellular morphology and apoptosis progression via a TUNEL based staining assay (Figure 5). The polymer–Dex–Dox and polymer–Dox hybrids produced enlarged cellular morphologies that were indicative of pre-apoptotic cells. Glass-only and polymer-only control slides produced cells with unaltered morphologies. In addition, though the same number of cells were seeded per slide, significantly fewer cells grew and propagated on the polymer–Dex–Dox and polymer–Dox hybrid slides. When staining for double stranded breaks indicative of apoptosis progression, none was seen in cells grown on glass or polymer only slides. However, in both the polymer–Dox and the polymer–Dex–Dox slides, an accumulation of apoptotic cells is observed (Figure 5). This is detected both by the TUNEL stain accumulation and also the shrinking of the apoptotic cells from their pre-apoptotic morphology. Once again this demonstrates a potent Dox dependent apoptosis inducing functionality to the polymer–Dex–Dox films.


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

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

Microscopy Dox impact upon cellular proliferation and morphology was demonstrated via confocal microscopy. Macrophages cultured atop glass or polymer only substrates produced highly confluent growth. Macrophages cultured atop polymer–Dox and polymer–Dex–Dox nanofilm hybrids generated decrease cell confluency, enlarged, preapoptotic cells, as well as shrunken apoptotic cells due to Dox-induced cell death/apoptosis. TUNEL assays demonstrate the progression of cells grown on polymer–Dox and polymer–Dex–Dox nanofilm hybrids to apoptosis.Notes: Magnification: 40X, Leica inverted microscope Confocal Laser Scanning System.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2636579&req=5

f5-ijn-3-425: Microscopy Dox impact upon cellular proliferation and morphology was demonstrated via confocal microscopy. Macrophages cultured atop glass or polymer only substrates produced highly confluent growth. Macrophages cultured atop polymer–Dox and polymer–Dex–Dox nanofilm hybrids generated decrease cell confluency, enlarged, preapoptotic cells, as well as shrunken apoptotic cells due to Dox-induced cell death/apoptosis. TUNEL assays demonstrate the progression of cells grown on polymer–Dox and polymer–Dex–Dox nanofilm hybrids to apoptosis.Notes: Magnification: 40X, Leica inverted microscope Confocal Laser Scanning System.
Mentions: Confocal microscopy also revealed the impact of Dox elution from the copolymeric nanofilm upon cellular morphology and apoptosis progression via a TUNEL based staining assay (Figure 5). The polymer–Dex–Dox and polymer–Dox hybrids produced enlarged cellular morphologies that were indicative of pre-apoptotic cells. Glass-only and polymer-only control slides produced cells with unaltered morphologies. In addition, though the same number of cells were seeded per slide, significantly fewer cells grew and propagated on the polymer–Dex–Dox and polymer–Dox hybrid slides. When staining for double stranded breaks indicative of apoptosis progression, none was seen in cells grown on glass or polymer only slides. However, in both the polymer–Dox and the polymer–Dex–Dox slides, an accumulation of apoptotic cells is observed (Figure 5). This is detected both by the TUNEL stain accumulation and also the shrinking of the apoptotic cells from their pre-apoptotic morphology. Once again this demonstrates a potent Dox dependent apoptosis inducing functionality to the polymer–Dex–Dox films.

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