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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

Confirmation of doxorubicin hydrochloride and dexamethasone drug incorporation into the PMOXA–PDMS–PMOXA triblock copolymer was performed via monitoring of surface pressure changes of fabricated Langmuir films. Subsequent drug activity trials confirmed the functionality of deposited hybrid material.
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f2-ijn-3-425: Confirmation of doxorubicin hydrochloride and dexamethasone drug incorporation into the PMOXA–PDMS–PMOXA triblock copolymer was performed via monitoring of surface pressure changes of fabricated Langmuir films. Subsequent drug activity trials confirmed the functionality of deposited hybrid material.

Mentions: Mixtures of copolymers with the drugs Dex and Dox were characterized via Langmuir isotherms and copolymer–Dex–Dox thin films were fabricated via Langmuir–Blodgett deposition. Figure 2 shows the compression isotherms for the PMOXA–PDMS–PMOXA triblock copolymer nanofilm alone or mixed with Dox, Dex, or both Dex and Dox. The variations in the isotherms of the copolymer–drug mixtures demonstrate that the readings were responsive to varied drug amounts and that this mixture was able to generate high surface pressure readings indicative of film formation. These graphs show that drug integration into the copolymer film occurs due to changes between compression phase transitions and maximum collapse pressures. These graphs are similar to the variations in surface pressure that have been seen when drugs have been incorporated into a copolymer thin film at the air-water interface using Langmuir–Blodgett (Pierstorff et al 2008). Copolymer films mixed with either Dex or Dox alone have been previously characterized and demonstrate incorporation of either drug into the copolymer matrix (Chow et al 2008; Pierstorff et al 2008). Interestingly, when both Dox and Dex are mixed with the copolymer nanofilm and compressed, the isotherm completely overlaps that of copolymer and Dex alone. Thus, even though the copolymer–Dox mixture alone has a shift in the isotherm (Figure 2; Pierstorff et al 2008), it appears that this is masked or overwhelmed by the presence of Dex in the mixture as well. While the mechanism driving this observation was unclear, Dox activity assays revealed its incorporation into the copolymer nanofilm.


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

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

Confirmation of doxorubicin hydrochloride and dexamethasone drug incorporation into the PMOXA–PDMS–PMOXA triblock copolymer was performed via monitoring of surface pressure changes of fabricated Langmuir films. Subsequent drug activity trials confirmed the functionality of deposited hybrid material.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-3-425: Confirmation of doxorubicin hydrochloride and dexamethasone drug incorporation into the PMOXA–PDMS–PMOXA triblock copolymer was performed via monitoring of surface pressure changes of fabricated Langmuir films. Subsequent drug activity trials confirmed the functionality of deposited hybrid material.
Mentions: Mixtures of copolymers with the drugs Dex and Dox were characterized via Langmuir isotherms and copolymer–Dex–Dox thin films were fabricated via Langmuir–Blodgett deposition. Figure 2 shows the compression isotherms for the PMOXA–PDMS–PMOXA triblock copolymer nanofilm alone or mixed with Dox, Dex, or both Dex and Dox. The variations in the isotherms of the copolymer–drug mixtures demonstrate that the readings were responsive to varied drug amounts and that this mixture was able to generate high surface pressure readings indicative of film formation. These graphs show that drug integration into the copolymer film occurs due to changes between compression phase transitions and maximum collapse pressures. These graphs are similar to the variations in surface pressure that have been seen when drugs have been incorporated into a copolymer thin film at the air-water interface using Langmuir–Blodgett (Pierstorff et al 2008). Copolymer films mixed with either Dex or Dox alone have been previously characterized and demonstrate incorporation of either drug into the copolymer matrix (Chow et al 2008; Pierstorff et al 2008). Interestingly, when both Dox and Dex are mixed with the copolymer nanofilm and compressed, the isotherm completely overlaps that of copolymer and Dex alone. Thus, even though the copolymer–Dox mixture alone has a shift in the isotherm (Figure 2; Pierstorff et al 2008), it appears that this is masked or overwhelmed by the presence of Dex in the mixture as well. While the mechanism driving this observation was unclear, Dox activity assays revealed its incorporation into the copolymer nanofilm.

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