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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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The copolymer-mediated sequestering and integration of multiple therapeutics into a single thin film is shown. Langmuir-Blodgett was used to deposit drug containing triblock copolymer films that can maintain drug incorporation for localized release. Combinatorial therapy at the surface of the material–tissue interface can provide significantly enhanced treatment produced by a noninvasive nanoscale platform. Copyright © 2008. Adapted from Pierstorff E, Krucoff M, Ho D. 2008. Apoptosis induction and attenuation of inflammatory gene expression in murine macrophages via multitherapeutic nanomembranes. Nanotechnology, 19:265103–12.
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f1-ijn-3-425: The copolymer-mediated sequestering and integration of multiple therapeutics into a single thin film is shown. Langmuir-Blodgett was used to deposit drug containing triblock copolymer films that can maintain drug incorporation for localized release. Combinatorial therapy at the surface of the material–tissue interface can provide significantly enhanced treatment produced by a noninvasive nanoscale platform. Copyright © 2008. Adapted from Pierstorff E, Krucoff M, Ho D. 2008. Apoptosis induction and attenuation of inflammatory gene expression in murine macrophages via multitherapeutic nanomembranes. Nanotechnology, 19:265103–12.

Mentions: Previously, we have demonstrated the use of polymethyloxazoline–polydimethylsiloxane–polymethyloxazoline (PMOXA–PDMS–PMOXA) block copolymer membranes for harnessing and releasing active anti-inflammatory and anti-cancer therapeutics (Chow et al 2008; Pierstorff et al 2008). This copolymer contains both hydrophilic and hydrophilic blocks which allows for the formation of copolymer-drug hybrids that incorporate therapeutics of virtually any type regardless of its hydrophilic or hydrophobic characteristics (Nardin et al 2000, 2001; Ho et al 2003, 2004). The polymer has also been shown to be biocompatible and is only 4 nm thick, making it noninvasive and an ideal candidate for a film based drug eluting platform for medical devices. This study has combined the benefits of thin film polymers with localized drug delivery to fabricate a block copolymer nanofilm capable of eluting multiple therapeutics from a single device (Figure 1). These include dexamethasone (Dex), a steroid based anti-inflammatory and doxorubicin hydrochloride (Dox), an anti-cancer therapeutic that induces cell death via apoptosis. Surface pressure isotherms were used to confirm film formation and drug mixing, and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), TUNEL-based cell staining, and DNA fragmentation studies were performed to ascertain drug release and function. Thus a multifunctional thin film coating to address multiple conditions simultaneously was created.


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

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

The copolymer-mediated sequestering and integration of multiple therapeutics into a single thin film is shown. Langmuir-Blodgett was used to deposit drug containing triblock copolymer films that can maintain drug incorporation for localized release. Combinatorial therapy at the surface of the material–tissue interface can provide significantly enhanced treatment produced by a noninvasive nanoscale platform. Copyright © 2008. Adapted from Pierstorff E, Krucoff M, Ho D. 2008. Apoptosis induction and attenuation of inflammatory gene expression in murine macrophages via multitherapeutic nanomembranes. Nanotechnology, 19:265103–12.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2636579&req=5

f1-ijn-3-425: The copolymer-mediated sequestering and integration of multiple therapeutics into a single thin film is shown. Langmuir-Blodgett was used to deposit drug containing triblock copolymer films that can maintain drug incorporation for localized release. Combinatorial therapy at the surface of the material–tissue interface can provide significantly enhanced treatment produced by a noninvasive nanoscale platform. Copyright © 2008. Adapted from Pierstorff E, Krucoff M, Ho D. 2008. Apoptosis induction and attenuation of inflammatory gene expression in murine macrophages via multitherapeutic nanomembranes. Nanotechnology, 19:265103–12.
Mentions: Previously, we have demonstrated the use of polymethyloxazoline–polydimethylsiloxane–polymethyloxazoline (PMOXA–PDMS–PMOXA) block copolymer membranes for harnessing and releasing active anti-inflammatory and anti-cancer therapeutics (Chow et al 2008; Pierstorff et al 2008). This copolymer contains both hydrophilic and hydrophilic blocks which allows for the formation of copolymer-drug hybrids that incorporate therapeutics of virtually any type regardless of its hydrophilic or hydrophobic characteristics (Nardin et al 2000, 2001; Ho et al 2003, 2004). The polymer has also been shown to be biocompatible and is only 4 nm thick, making it noninvasive and an ideal candidate for a film based drug eluting platform for medical devices. This study has combined the benefits of thin film polymers with localized drug delivery to fabricate a block copolymer nanofilm capable of eluting multiple therapeutics from a single device (Figure 1). These include dexamethasone (Dex), a steroid based anti-inflammatory and doxorubicin hydrochloride (Dox), an anti-cancer therapeutic that induces cell death via apoptosis. Surface pressure isotherms were used to confirm film formation and drug mixing, and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), TUNEL-based cell staining, and DNA fragmentation studies were performed to ascertain drug release and function. Thus a multifunctional thin film coating to address multiple conditions simultaneously was created.

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