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June 27, 2003 – Small tech is helping medicinal molecules such as proteins, peptides, genes and vaccines reach the right destination with greater precision, speed and control. And the mechanisms — including implants, particles and patches — are as varied as the types of payloads delivered.
Researchers at McGill University in Montreal recently created a “nanopill” from two polymer molecules — one water-repellant, the other hydrophobic — that self-assemble into a sphere called a micelle. In tests, the 20-45 nanometer structures were small enough to pass through the wall of an animal cell and deliver their cargo of drugs to specific structures within the cell.
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Delivering materials directly inside targeted cells could, for example, improve cancer treatments and help reduce side effects. It also holds promise as a better way to offer gene therapies for DNA defects such as cystic fibrosis. Insert Therapeutics Inc. in Pasadena, Calif., and Berlin-based Capsulution NanoScience AG are just two companies working on ways to deliver drugs inside cells.
MicroCHIPS Inc. of Bedford, Mass., is working on a silver dollar-size device to implant under a patient’s skin or in the abdomen that would provide tiny, precise doses of hormones, pain medication or other pharmaceuticals. The chips, made of silicon or polymer, feature hundreds of tiny micromachined wells that can be loaded with a mixture of medicines. A microcontroller could release small amounts of different chemicals on a customizable schedule. Or biosensors could trigger releases by detecting blood sugar levels or other biochemical conditions.
If approved in four to five years, such a device could provide diabetics with doses of insulin so that they could forgo daily injections for as much as a year. Or it could help liberate HIV patients from following complicated daily regimens of multiple medications. To more closely imitate how the body releases hormones, the device could dispense compounds such as estrogen in periodic bursts.
Nano coats
Through its Nanocoat technology, Nanotherapeutics Inc. in Alachua, Fla., can apply a layer of biodegradable polymer a few nanometers thick around drug micro-
particles. The coating prevents the drug from being broken down by enzymes and acids in the stomach so that more of the active ingredient will reach the bloodstream through the intestinal tract.
Nanotherapeutics President James Talton noted that pharmaceutical compounds that aren’t soluble in water could also be packaged or coated in ways to increase their “bioavailablity,” the amount of material that gets absorbed where needed. With many substances, as little as 10 percent reach their intended destination. Improving bioavailabilty could also reduce drug cost by decreasing the amount of active material required per dose.
About a third of all new drug candidates aren’t very soluble. And pharmaceutical companies often abandon test compounds with low bioavailabilty. Talton said that Nanotherapeutics is in early stages of development, but wants to help pharmaceutical companies deliver their existing compounds more effectively and help new candidates that might otherwise get orphaned.
ALZA Corp.’s STEALTH technology uses specialized microscopic spheres called liposomes to encapsulate anticancer drugs. A coating of polyethylene glycol around the liposome prevents the body’s immune system from attacking the drug-fighting agent before it reaches the target cancer cells. Camouflaging the spheres could make them a better way to provide chemotherapy.
Controlling the dosage
Intravenous injections are one of the most immediate ways to deliver a medication, but aren’t usually the best way to deliver drugs at a controlled rate. London-based SkyePharma PLC has come up with a delivery system called DepoFoam based on lipid micro-spheres with hundreds of minute chambers that can be loaded with drug molecules. As the honeycomb of chambers biodegrades, they gradually release their pharmaceutical packages. The rate of release can be regulated by modifying the lipids during production.
Skin patches have been around since 1981 and they’re currently used to deliver estrogen for hormone replacement therapy, compounds for birth control and nitroglycerin to control angina, to name a few. ALZA Pharmaceuticals’ E-TRANS patch pushes pain-killing fentanyl molecules through the skin via electric pulses. Sontra Medical Corp. in Franklin, Mass., is using ultrasound to drive medicines through the skin in its SonoPrep device.
NanoPass Technologies Ltd. in Haifa, Israel, uses MEMS production techniques to fabricate a square of silicon or polymer with an array of up to 600 micropyramids that is applied to the skin like a patch. The goal of the company’s MicronJet product is to deliver large molecules such as proteins, peptides and vaccines that otherwise can’t pass through the skin.