Advanced Technology - Microencapsulation

Microgravity offers novel advantages for working with multiphase fluid systems.  Research in this area has led a new method for making liquid-filled microcapsules, which is a unique and versatile drug delivery system.  Microcapsules are designed to deliver anti-tumor drugs.  To date, 11 different drugs have been encapsulated, including two anti-tumor drugs, an immune stimulant, antibiotics, a clot-dissolving enzyme, and an anti-nausea drug. External - Triggered Microcapsules (E-T) also have been developed, which can release drug upon application of external magnetic fields.

By injecting microcapsules into the small arteries that lead into solid tumors, the capsules form emboli.  These emboli block the blood supply and slowly release drug inside the tumor without affecting the surrounding normal tissue.  Co-encapsulation of a radio-contrast medium allows C-T radiographic three-dimensional mapping of the microcapsule distribution within the tumor tissue.  To ensure maximum destruction of the tumor, additional microcapsules can be injected so that tumor capillaries are fully loaded.

This new microcapsule technology presents numerous opportunities for collaborations to develop new drug delivery systems.  Product development is focused on tissue culture, animal studies, and clinical trials that use Earth-based scale-up and production technology.  For selected projects, however, some space flight experiment opportunities also are available via the NASA Biological Systems Office and commercial Space Product Development programs.

Experiments on Orbit

To expand microencapsulation research, a special Microencapsulation and Electrostatic Processing System (MEPS) was flown on STS-95 by Senator John Glenn, NASDA astronaut Dr. Chiaki Mukai, and European Space Agency astronaut Pedro Duque. The MEPS experiments on STS-95 successfully produced microcapsules containing three different types of anti-tumor drugs. Three sets of experiments compared the encapsulation efficiencies of the MEPS, a DMDA type apparatus [ITA, Inc., Exton, PA], and a specially modified ADSEP system [SHOT, Inc., Greenville, IN]. The results of the STS-95 experiments showed that each of the three apparatus had unique advantages, depending on the type of experiments. The MEPS showed great promise for space experiments designed understand the limitations of fluid shear, pressure, and temperature in scale-up and ground-based commercial production. Therefore, NASA assembled a team to construct a second version of the MEPS (MEPS-II) which was designed specifically to operate aboard the ISS.

The revised Microencapsulation Electrostatic Processing System (MEPS-II) occupies one-half of an Express Rack locker, including rear-air cooling and an improved crew display specifically for research in the International Space Station and Shuttle Middeck.  The MEPS-II was first flown on UF-1 in November 2001, but experiment modules were not flown and the unit was returned for further testing.  The first microencapsulation experiments on the ISS were conducted by Science Officer, Dr. Peggy Whitson during Increment 5 operations (July 2002).  She conducted a total of 8 experiments during that mission.

Microencapsulation experiments on the ISS provide valuable insight into improving manufacturing and scaling up production for clinical trials and new therapeutic uses.

The main research focus was to repeat STS-95 experiments to better understand the limitations of the fluid flows and g- dependent forces during the microencapsulation process.  These studies included:

• formation of anti-tumor micro-capsules containing drugs for "chemoembolization" of vascularized tumors,
• formation of microcapsules containing a photo-activated drug which can be used for photodynamic therapy of solid tumors by activation with near infrared light (630 nm),
• co-encapsulation of magnetic trigger particles and anti-tumor drugs, and
• encapsulation of plasmid DNA.

Learn more about microencapsulation in both flight hardware and laboratory.

Anti-tumor Microcapsules: a new drug delivery system for treating solid, vascular tumors

Like miniature liquid-filled balloons, multi-layered microcapsules have been made to contain dissolved drugs and a radio-contrast oil.  Microcapsules manufactured in microgravity are designed for "chemoembolization" of solid, not a therapeutic approach that lacks the usual side effects of systemic chemotherapy.  The microcapsules are carried in the blood flow into the small arterioles within the tumor wherein they pack tightly to form an artificial embolus.  The microcapsules kill the tumor cells by reducing the blood flow within the tumor tissues, and by releasing the anti-tumor drug slowly through the permeable outer "skin" of the capsule.  Until recently, these new microcapsules could only be formed under microgravity conditions.  After several Shuttle flights, we have developed special formulations and apparatus that now enable microcapsule production on Earth.

Continuing product development includes microgravity experiments for optimizing drug loading, size distributions, and various scale-up production methods.  Studies at the Texas A&M College of Veterinary Medicine are optimizing the C-T scanning of the microcapsules in rabbit kidneys as a model for three-dimensional imaging in the target tumors.

Photodynamic Therapy:  a non-invasive approach for drug activation and stimulating cellular repair

Photodynamic therapy is a therapeutic approach that activates light-sensitive drugs or compounds using near-infrared light (NIR) at 630 nm.  Special microcapsules are made containing the photo-activated drug PhotofrinTM or benzo-porphyrin derivative (BPD).  Other applications of NIR light include the ability to:

• Increase the rate of tissue repair of open epidermal and connective tissue wounds,
• Treat severe mouth ulcers in immunologically compromised children following radiotherapy,
• Treat superficial cuts and severe abrasions, in submariners, and
• Increase the rate of bone regeneration surrounding dental implants.

NASA researchers are evaluating NIR light therapy as a potential countermeasure for long-duration space missions and for remote medical care on Earth.  Current studies include: cellular mechanisms of combined effects of radioprotectants, cytokine inducers, and microgravity effects on various immune cell functions using the horizontal rotating bioreactors to model microgravity.

Microencapsulation of Cells and Cell Aggregates:  new options for transplantation

Single cells or cell aggregates can be encapsulated for transplantation to allow:

• secretion of specific agents such as hormones or cytokines,
• reformation of bone, and
• initiation of nerve tissues annealing.

Different agents can be co-encapsulated in the same microcapsules, along with cells or cell aggregates, to study molecular mechanisms that inhibit the immune cytotoxic response.

External Triggered (E-T) Microcapsules:  acute drug release after exposure to external magnetic fields

A special purpose microcapsule system has been developed to lyse open the capsules upon the application of a harmless external magnetic or ultrasonic field.  This allows for burst release of the drugs inside and collapse of the microcapsules when the physicians decide that the slow drug release by diffusion through the outer wall is no longer desired.  The External-Triggered (E-T) microcapsules are made so that each one contains tiny ferromagnetic particles designed to heat up in a magnetic field.  The "trigger particles" become just hot enough to melt a hole in the outer skin thus releasing the contents of the microcapsule upon command.  The E-T Microcapsules are designed to be triggered by diagnostic levels of Magnetic Resonance Imaging (MRI) fields long after the microcapsules have been injected into the tissue.  Current research also includes uses of ultrasonic imaging catheters and drug releasing mechanisms.

Publications on Microencapsulation in Microgravity

1. D. R. Morrison, B. Mosier, and J. M. Cassanto. Microencapsulation of Anti-tumor, Antibiotic and Thrombolytic Drugs in Microgravity, Proceedings of the Technology 2003 Conference on National Technology Transfer, NASA Publication CP-3249. Anaheim, CA. December 1993, pp.117-126, 1994.
2. D. R. Morrison, B. Mosier, and J. M. Cassanto. Immiscible-phase Microencapsulation of Drugs in Microgravity, in R.A. Schiffman and J.B. Andrews (Eds.), 6th International Symposium on Experimental Methods for Microgravity Materials Sciences. Minerals, Metals and Materials Society: Warrendale, PA. pp. 199-207, 1994.
3. D. R. Morrison and B. Mosier. Microencapsulation of Drugs in Microgravity: A New Drug Delivery System for Chemoembolization of Vascular Tumors. Paper # 95-LS-39, NASA/AIAA, Life Sciences and Space Medicine Conference, Houston, TX. April 1995.
4. B. M. Mosier, and D. R. Morrison. Multi-lamellar Microcapsules Created in Microgravity for Dual Drug Chemoembolization. Proceedings of the International Symposium Controlled Release of Bioactive Material, 22:180-181. 1995.
5. Farmer, Linda. NASA Launches Monoglycerides into Space. Inside Eastman (Tennessee Division), Volume 15 14:4, July 18 1996. ^*
6. J.M. Cassanto and B.M. Mosier. New Methods for Space Processing Research; The Dual Material Dispersion Apparatus: A Second Generation Automated Microgravity Processing Laboratory. Low G, 8:3. September 1997.
7. D. R. Morrison, B. Mosier, and J. M. Cassanto, Low Shear Encapsulation of Multiple Drugs. Low G, Vol.9 No. 1:19-22, March 1998.

^* This appeared in the Eastman publication written about the microencapsulation of drugs (Mosier and Morrison) on STS-77.