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Risperdal delivers the drug risperidone encapsulated in poly(lactide-co-glycolide) (PLGA) biodegradable polymeric microspheres with a particle diameter of about 100 microns via intramuscular injection once every two weeks. The drug is released over time from the particles by slowly diffusing out of the polymeric matrix as water diffuses in and as the polymer chains degrade via hydrolysis, causing particles to lose their structure and fall apart. PLGA-based particle drug-delivery systems can be tailored to the properties of the drug, appropriate dosage, and the mechanism of action for releasing the encapsulated drug over a period of weeks or months in a controlled way.

Risperdal®, the original risperidone product, is taken orally by patients with schizophrenia on a daily basis. In most cases, the simplicity of taking a pill is very strongly preferred as a method of administering a drug, and designing a drug-delivery system to change the administration from oral delivery to a more complicated (e.g., inhalation) or painful (e.g., injection) delivery, would normally be unsuccessful (unless the oral drug had a significant shortcoming).

For patients with schizophrenia, however, taking a pill every day can be problematic, and missing a dose one day can lead to a downward spiral of missing more doses. In this case, intramuscular injection administered by a doctor or nurse once every two weeks has not only increased patient compliance, but also improved the efficacy of the drug, resulting in a significant improvement in the treatment of patients with schizophrenia.

Microparticle delivery systems, such as Risperdal CONSTA, are too big to be administered intravenously. Their particle size would result in very fast clearance by the body’s defense mechanisms or could potentially pose a significant safety risk if they were to lodge in capillary beds in the heart or lungs. Nanoparticle-based drug-delivery systems, in which particle sizes generally range from about 20 to 200 nanometers, are being investigated for delivering therapeutic agents, imaging diseased tissues or organs, and sensing the effectiveness of drug delivery or the status of disease. As a point of reference, a nanometer is one-billionth of a meter or one-millionth of a millimeter. Because of their very small size, nanoparticles administered systemically (i.e., by intravenous injection or infusion) circulate through the bloodstream carrying their therapeutic payloads directly to the site of disease in the body.

NANOPARTICLE-BASED DRUG-DELIVERY SYSTEMS

Diseases associated with defects or irregularities in the endothelial cells of blood vessels in the diseased area, creating what is called “leaky vasculature,” may be particularly susceptible to treatment by nanoparticle-based drug-delivery systems. These include inflammatory diseases (e.g., rheumatoid arthritis, atherosclerosis), infectious diseases (e.g., tuberculosis), and cancer. Once nanoparticles reach the affected area, they can passively diffuse from the bloodstream across the leaky vasculature to deliver drugs directly to the disease site.



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