In an advanced method of administering drugs to target sites in human bodies, the drugs in liquid form are contained in microcapsules that are injected, and then, by exposing the target sites to externally generated electromagnetic fields, the microcapsules are lysed to release the drugs. Such externally triggered microcapsules are intended primarily for use in combined-modality therapies of cancer. In a given application, the external electromagnetic field can be applied to cause the release of the encapsulated drug(s) at a prescribed time or when the microcapsules are confirmed to be located in a specific tissue.
The concept of microencapsulation of drugs was reported in “Microencapsulation of Multiple Drugs” (MSC-22489), NASA Tech Briefs, Vol. 20, No. 11 (November 1996), page 92. More recently, an external-triggering method related to the present method was reported in “In Situ Activation of Microencapsulated Drugs (MSC-22866),” NASA Tech Briefs, Vol. 24, No. 9 (September 2000), page 64. A microcapsule of the type used in the present method is a multilayer structure that contains a concentrated drug solution. The outer layer of the microcapsule is a polymeric membrane that is both transparent to electromagnetic radiation and insoluble in aqueous fluids. Also contained within the microcapsule, in a compartment next to the outer membrane, is a fluid-filled compartment that contains one or more ferromagnetic thermoparticles.
The microcapsules are designed to be injected into arteries that lead to vascularized tumors or other target tissues (see figure). The outer-membrane polymer and the thermoparticle material are chosen so that the Curie temperature of the thermoparticles exceeds the melting temperature of the polymer. When the microcapsule-infused target region is exposed to an electromagnetic field of suitable frequency and power density for a specified short time (minutes), the electromagnetic field heats the thermoparticles. The localized heating of the thermoparticles melts a hole in the outer polymeric membrane, thus releasing the drug to the surrounding tissue.
Because the thermoparticles absorb the electromagnetic radiation much more strongly than do the surrounding microcapsule materials and tissues, an electromagnetic field of relatively low power can be used to effect drug release. Regulating the exposure to the electromagnetic field is not a major problem: Heating is automatically limited to the Curie temperature because above that temperature, the thermoparticles lose their ferromagnetism and thereby become less absorbent to the electromagnetic field.
The ferromagnetic material of thermoparticles can be formulated to have Curie temperatures as high as 80 °C, but because the thermoparticles are typically smaller than 1 µm, heating can be localized well enough to prevent widespread thermal damage to the surrounding tissue. Of course, depending on the application, additional therapeutic advantage might be gained by changing the frequency and/or power of the electromagnetic field, after the microcapsules have been lysed, to obtain controlled hyperthermia to enhance the local effectiveness of the drugs that have been released. In some applications, it could be desirable to effect multiple releases of the same drug or different drugs by use of injecting mixtures of microcapsules containing ferromagnetic particles with different Curie temperatures that could be triggered at different times, as determined by the strength of the electromagnetic field and the duration of exposure.
This work was done by Dennis R. Morrison and Benjamin Mosier of Johnson Space Center.
This invention is owned by NASA, and a patent application has been filed. Inquiries concerning nonexclusive or exclusive license for its commercial development should be addressed to
the Patent Counsel
Johnson Space Center
Refer to MSC-22939.