Proprietary Liposomal Technology
Insmed's proprietary liposomal technology is designed specifically for delivery of pharmaceuticals to the lung and provides for potential improvements to the conventional inhalation methods of delivering drug to the pulmonary system. These potential advantages include improvements in efficacy, safety and patient convenience.
Underpinning these potential advantages are the following four factors:
Sustained effect of drug in the lung — The liposomes maintain drug in the lung and thus provide a sustained benefit to the lung, which may be important in treating certain bacterial infections that have a significant pulmonary component. Maintenance of anti-bacterial drug levels in the lung above the minimum inhibitory concentration (MIC) for prolonged time periods is an important element in the effectiveness of antibiotics; in a plot of drug concentration in the lung over time the area under the concentration curve (AUC) reflects drug exposure;
Charge-neutral liposomes — Insmed's liposomes can be charge neutral, which may be an important factor in effectively penetrating through any patient mucus and bacterial biofilm. Aminoglycosides such as amikacin are antibiotic compounds that have a positive charge because of their chemical structure. The materials found in a patient's mucus have a negative charge. Biofilms which are produced by bacteria to protect themselves also have a negative charge. Because opposite charges attract each other the positively charged antibiotics bind to the negatively charged compounds on the surfaces of the mucus and biofilm. This binding prevents effective penetration of positively charged antibiotic drugs into the spaces in which the bacteria are located. We believe the neutrally charged Insmed liposomes may enable greater penetration into the mucus and biofilm to provide higher concentrations of drug to kill the bacteria.
Potential for Increased Efficacy and with Low Drug Toxicity— A potential benefit of Insmed's inhalation drug delivery technology may be enhanced efficacy as a result of larger amounts of the drug being delivered directly to the site of disease. With higher localized antibiotic concentrations bacterial infections are more readily treated. Another advantage of localized targeting of drugs using this unique delivery system is that non-disease sites throughout the body are exposed to significantly less drug. We believe this reduces the potential for the occurrence of any drug-related toxicity.
High efficiency drug encapsulation — Insmed's liposomes are designed to encapsulate very high concentrations of drug into relatively small liposome structures. This efficiency allows Insmed's compact, drug-laden liposomes to physically penetrate bacteria-generated biofilms in pre-clinical models. Further, drug is released from the liposomes near the site of infection. And the bacteria produce disruptive factors that cause the liposome to open and release its' drug contents near to where the bacteria reside.
Endogenous lipid excipients — We believe this may reduce the chance of adverse reactions. The lipid components of Insmed's compounds are the same as those found naturally in the lung, which may ensure a more natural metabolism and clearance than other drug delivery systems, for example, particles comprised of man-made polymers containing drug. This may reduce the chance of adverse reactions.
We believe that Insmed's liposomal technology can be used for the successful delivery of low molecular weight products like classic pharmaceuticals as well as high molecular weight compounds such as peptides, proteins and genes. Insmed's unique lipid-based delivery systems are not dependent on the inhalation device and can be administered either as a nebulized aerosol spray or as a dry powder.
Liposomes are microscopic shells that usually have a single membrane containing water inside. Liposomes can also be designed to have several membrane layers. These layers may be arranged like the layers of an onion or like bubbles inside of larger bubbles. In all cases, there is water in the liposome's core and between each layer. In a liposome drug delivery system, the drug is trapped in the liposome and then administered to the patient during treatment. Drugs that dissolve in water would be located in the liposome's water core, while drugs that do not dissolve in water may be found in or associated with the membrane layers.
