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Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection

View Article: PubMed Central - PubMed

ABSTRACT

Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it’s drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine.

No MeSH data available.


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(a) CT images showing capsules coated in wax only (Eicosane), iron-oxide wax coating, and the iron oxide-wax coated capsules filled with BaSO4, Perfluorooctylbromide (PFOB), and Iohexol. (b) Quantification of radiopacity of the capsules shown in (a). Bars show mean X-ray absorbance of all pixels contained within the capsule coating or filling, error bars show SD of the whole segmented region in the capsule cavity. The absorbance of air, water, abdomen soft tissue, and bone are provided for reference.
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f5: (a) CT images showing capsules coated in wax only (Eicosane), iron-oxide wax coating, and the iron oxide-wax coated capsules filled with BaSO4, Perfluorooctylbromide (PFOB), and Iohexol. (b) Quantification of radiopacity of the capsules shown in (a). Bars show mean X-ray absorbance of all pixels contained within the capsule coating or filling, error bars show SD of the whole segmented region in the capsule cavity. The absorbance of air, water, abdomen soft tissue, and bone are provided for reference.

Mentions: One potential limitation of iron-based contrast agents for MRI is the “blooming” effect, whereby signal hypo-intensity is produced over a greater area than that which contains the contrast agent, Fig. 5. Though this can increase the sensitivity with which iron oxides can be detected, it can also reduce the accuracy of locating the contrast agent, as well as obscuring anatomical features that might be important for reference when targeting delivery. A second limitation is the potential inability to distinguish between the presence of T2 contrast agents such as iron oxides, and endogenous areas of signal hypo-intensity and susceptibility artefacts caused by gas/tissue interfaces in the bowel. For these two reasons, we next chose to investigate the incorporation of X-ray CT contrast agents into the capsules, which should provide the advantages of both positive contrast and a less ambiguous mode of detection. Furthermore, the use of CT is significantly cheaper and quicker than MRI in the clinic, providing a better option for translation. CT scanning is sufficiently fast as to give a pinpoint location of the capsule. Gastrointestinal transit time may be increased or decreased with the use of appropriate binding medication or laxatives respectively to aid detection49505152. In this way, hyperosmotic agents increase the water content of the intestine and so can change the environment in which the delivery occurs. This is advantageous in both detection and drug release and diffusion.


Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection
(a) CT images showing capsules coated in wax only (Eicosane), iron-oxide wax coating, and the iron oxide-wax coated capsules filled with BaSO4, Perfluorooctylbromide (PFOB), and Iohexol. (b) Quantification of radiopacity of the capsules shown in (a). Bars show mean X-ray absorbance of all pixels contained within the capsule coating or filling, error bars show SD of the whole segmented region in the capsule cavity. The absorbance of air, water, abdomen soft tissue, and bone are provided for reference.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037467&req=5

f5: (a) CT images showing capsules coated in wax only (Eicosane), iron-oxide wax coating, and the iron oxide-wax coated capsules filled with BaSO4, Perfluorooctylbromide (PFOB), and Iohexol. (b) Quantification of radiopacity of the capsules shown in (a). Bars show mean X-ray absorbance of all pixels contained within the capsule coating or filling, error bars show SD of the whole segmented region in the capsule cavity. The absorbance of air, water, abdomen soft tissue, and bone are provided for reference.
Mentions: One potential limitation of iron-based contrast agents for MRI is the “blooming” effect, whereby signal hypo-intensity is produced over a greater area than that which contains the contrast agent, Fig. 5. Though this can increase the sensitivity with which iron oxides can be detected, it can also reduce the accuracy of locating the contrast agent, as well as obscuring anatomical features that might be important for reference when targeting delivery. A second limitation is the potential inability to distinguish between the presence of T2 contrast agents such as iron oxides, and endogenous areas of signal hypo-intensity and susceptibility artefacts caused by gas/tissue interfaces in the bowel. For these two reasons, we next chose to investigate the incorporation of X-ray CT contrast agents into the capsules, which should provide the advantages of both positive contrast and a less ambiguous mode of detection. Furthermore, the use of CT is significantly cheaper and quicker than MRI in the clinic, providing a better option for translation. CT scanning is sufficiently fast as to give a pinpoint location of the capsule. Gastrointestinal transit time may be increased or decreased with the use of appropriate binding medication or laxatives respectively to aid detection49505152. In this way, hyperosmotic agents increase the water content of the intestine and so can change the environment in which the delivery occurs. This is advantageous in both detection and drug release and diffusion.

View Article: PubMed Central - PubMed

ABSTRACT

Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it’s drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine.

No MeSH data available.


Related in: MedlinePlus