Limits...
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.


CT images show iron-oxide wax coated capsules containing CT contrast agents before and after triggered release (60 minutes).Post-release images show the distribution of the released contrast agents.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5037467&req=5

f6: CT images show iron-oxide wax coated capsules containing CT contrast agents before and after triggered release (60 minutes).Post-release images show the distribution of the released contrast agents.

Mentions: Next, water-based phantoms containing the capsules with CT contrast agents were prepared. For the imaging to provide representative information on drug release, it is important to have contrast agents that behave in a similar way to the encapsulated drug of interest, so that their release from the capsule and absorption or trafficking in the bowel would be similar to that of the drug. For this reason the three CT contrast agents were selected to display different physical behaviour- BaSO4 (insoluble, granular), PFOB (liquid, immiscible in water), and Iohexol (powdered, soluble in water). In particular, the PFOB and BaSO4 mimic poorly soluble drugs with limited bioavailability, and any dissolution steps any such drug might have to overcome, for example if it was encased in an amphiphilic polymer585960. These were imaged before and after release, to assess the ability of CT to visualise dispersal of the capsule contents. Figure 6 shows that contents release can be visualised with BaSO4, PFOB, and Iohexol filled capsules. In the case of BaSO4 and PFOB, in which the contents are not soluble in water, the released contents can be seen lining the base of the tube of water into which they have been released. In the case of Iohexol, which is water soluble, it can be seen that the contrast agent has dissolved, confirming that the contents of the capsule have been exposed to the exterior aqueous environment after heating.


Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection
CT images show iron-oxide wax coated capsules containing CT contrast agents before and after triggered release (60 minutes).Post-release images show the distribution of the released contrast agents.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: CT images show iron-oxide wax coated capsules containing CT contrast agents before and after triggered release (60 minutes).Post-release images show the distribution of the released contrast agents.
Mentions: Next, water-based phantoms containing the capsules with CT contrast agents were prepared. For the imaging to provide representative information on drug release, it is important to have contrast agents that behave in a similar way to the encapsulated drug of interest, so that their release from the capsule and absorption or trafficking in the bowel would be similar to that of the drug. For this reason the three CT contrast agents were selected to display different physical behaviour- BaSO4 (insoluble, granular), PFOB (liquid, immiscible in water), and Iohexol (powdered, soluble in water). In particular, the PFOB and BaSO4 mimic poorly soluble drugs with limited bioavailability, and any dissolution steps any such drug might have to overcome, for example if it was encased in an amphiphilic polymer585960. These were imaged before and after release, to assess the ability of CT to visualise dispersal of the capsule contents. Figure 6 shows that contents release can be visualised with BaSO4, PFOB, and Iohexol filled capsules. In the case of BaSO4 and PFOB, in which the contents are not soluble in water, the released contents can be seen lining the base of the tube of water into which they have been released. In the case of Iohexol, which is water soluble, it can be seen that the contrast agent has dissolved, confirming that the contents of the capsule have been exposed to the exterior aqueous environment after heating.

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.