Proprietary Liposomal Technology
Insmed's proprietary liposomal technology is designed specifically for delivery of pharmaceuticals to the lung. We believe this liposomal technology 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.
What Are Liposomes?
Liposomes are microscopic membrane shells that contain water. Liposomes usually have a single membrane but can also be designed to have several membrane layers. These layers can 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 contained in the liposome and the liposomes are, administered to the patient during treatment. Water-soluble drugs are be located in the liposome's water core, and drugs that do not dissolve in water are located in or associated with the membrane layers.
Highlights of our Liposomal Technology
We believe neutrally charged liposomes may enable greater penetration into the mucus and biofilm, thereby providing higher drug concentrations to kill bacteria that produce the biofilm. The materials found in a patient's mucus have negative charges, and biofilms that are produced by bacteria to protect themselves also have negative charges. Because opposite charges attract each other, positively charged antibiotics, like amikacin, 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. Specifically in the case of Pseudomonas lung infections in CF patients, these barriers are the patient's own sticky mucu and bacteria's protective biofilm. In the case of NTM lung infections, the barrier to effective treatment is in gaining access to the interior of infected macrophages. ARIKACE liposomes are effective delivery systems that penetrate these barriers and provide high levels of drug in the lung for a long time.
Reference: Meers P, Neville M, Malinin V, Scotto AW, Sardaryan G, Kurumunda R, Mackinson C, James G, Fisher S, Perkins WR (2008) Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections. Journal Antimicrob Chemother Apr;61(4):859-68.
A potential benefit of Insmed's inhalation drug delivery technology over systemic delivery of the same drug may be enhanced efficacy as a result of greater 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.
Insmed's liposomes are designed to encapsulate very high concentrations of drug into relatively small liposome structures. According to pre-clinical models, this efficiency allows Insmed's compact, drug-laden liposomes to physically penetrate bacteria-generated biofilms. Further, we have found that drug is released from the liposomes by disruptive factors secreted by Pseudomonas, which we believe will cause liposomes to release their drug contents near to where the bacteria reside in the lungs.
We believe the ability to release drug contents in proximity to the bacteria may reduce the chance of systemic 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 such as particles comprised of man-made polymers containing drug.
Insmed's liposomal technology is key to both the retention of amikacin in the lung, which allows once-a-day dosing, and the ability of ARIKACE to gain close access to bacteria either within a biofilm, as in the case of CF patients, or within infected microphages, as in the case of NTM patients. It is localization near the bacteria that may improve effeciacy by allowing high concentrations of drug to be delivered where it is needed most.
With a neutral surface charge and small size, ARIKACE liposomes are able to effecively penetrate the thick CF mucus and the bacteria's protective biofilm, both of which we believe resrict the availability of unencapsulated animoglycosides such as tobramycin and amikacin. ARIKACE liposomes are also readily taken up by immune cells in the lung (alveolar macrophages) that "eat" inhaled particles. When NTM infect these immune cells, they are usually sheltered against attack from external antibiotics, but with ARIKACE, the uptake of the liposomes allows the drug to get inside these cells to attack the organisms.
*Administered once daily using an optimized eFlow® Electronic Nebulizer (PARI Pharma GmbH).