Dec 03

A novel drug delivery system that resists gastric degradation and can target specific cells

Drug delivery, Life Sciences 4 Comments »

Patent Title: Polymerized liposomes targeted to M cells and useful for oral or mucosal drug delivery

Inventors and Affiliation – Hongming Chen (Director of Formulation, Transform Pharmaceuticals), Robert S Langer (Institute Professor, MIT).

Key Words- Liposome, polymerized, lectin, vaccine, targeted delivery

The main focus of the patent

The patent describes a method to make micro vesicles called liposomes that are used to encapsulate drugs and vaccines for uptake by cells. Previously developed liposomes had to be administered by injection since they were destroyed by the harsh environment in the gastric tract when given orally. However the liposomes described in this patent have been chemically modified (by polymerization) to make the coating strong enough resist destruction by the gastric acid and intestinal enzymes. Additionally, carbohydrate molecules called lectins have been attached on their surface that help them bind to and be taken up by specific immune cells in the intestine. As a result, these vesicles can be designed to contain different vaccines, allergens and drugs and given orally without destruction and leakage of the agents before they reach and concentrate at the site of intended action.

Limited technical details

The drug delivery system patented comprises mainly of 3 components.

  1. At the core is a drug or vaccine (in which case it comprises of an antigen to evoke the immune response and an adjuvant to facilitate it). These are typically hydrophobic and need to be encapsulated in a lipid bilayer in order to be taken up by cells.
  2. The core is encapsulated in an envelope that has phospholipid molecules covalently bonded to each other at varying degrees thereby increasing its ability to withstand destruction by gastric acid and intestinal enzymes.
  3. The targeting molecule may be, for example, a carbohydrate (lectin) attached to the surface of the capsule that is recognized and bound by specific cells (in this case immune cells in the Peyer’s patch of the intestine) thereby facilitating the uptake of these vesicles by them. Other targeting molecules can include various carbohydrates, monoclonal antibodies, antibody fragments, viral proteins, bacterial proteins and magnetic particles.

Implications/applications and sectors that are addressed by patent/technology

This technology offers a drug delivery system to target specific cell or organs as intact particles where they can release the drug/antigen after uptake by the cells. Based on a variety of agents that can serve as the core (different drugs, vaccines, antigens etc) and the possible modifications on the surface to target various cells or tissues, a wide variety of applications can be approached with this patent.  It will be specifically useful in offering orally or mucosally administrable alternatives in conditions where the agent needs to bypass gastric and intestinal destruction and targeted to specific cells. The patent describes the delivery of a wide variety of compounds, allergens and antigens, including, but not limited to insulin peptides, diphtheria toxin antigens and influenza antigens as well as chemotherapy agents for the treatment of cancer; cytokines, including interferon; and hormones including insulin, human growth hormone (HGH), fertility drugs, calcitonin, calcitriol and other bioactive steroids.

History of the Inventors:

Hongming Chen: Chen was involved in founding TransForm Pharmaceuticals, a company engaged in the development of pharmaceutical products and based in Lexington, MA  in 1999. Chen is currently the director  of formulation development at Transform (which is now a subsidiary of the Johnson & Johnson group of companies).

Robert Langer: Langer is an extremely successful inventor and holds more than 600 granted or pending patents. He has been involved in the creation of about 25 companies and serves as a director on the boards of Echo Therapeutics, Inc., a medical device and pharmaceutical company, Momenta Pharmaceuticals, Inc., a biotechnology company developing drugs based on sugar sequencing technology, Alseres, Inc., a company focused on research and development of therapeutic and diagnostic products, and Wyeth, a pharmaceutical and consumer healthcare products company.

Similar Patents

US Patent Application 20090162424: Compositions and methods for making and using multifunctional polymerized liposomes

US Patent 6187335: Polymerizable fatty acids, phospholipids and polymerized liposomes therefrom

US Patent 6350466: Targeted polymerized liposome diagnostic and treatment agents

Patentgo’s opinion:

Liposomes which are microscopic phospholipid bubbles are an innovative form of drug delivery to administer a wide range of drugs and vaccines that would otherwise be easily degraded in the blood. There is an attraction in developing orally administrable forms of liposomes that resist the gastric acid to avoid the necessity of parenteral administration. The current invention not only offers resistance to gastric acid, but also combines a targeting molecule to selectively concentrate the drug at specific cell types. However the applications tried by the inventors have only been partially successful and they need to explore alternate applications since the model of combining the liposome with different drugs in the core and targeting molecules on the surface offers a lot of possibilities. Simultaneously they would have to compete with alternate technologies such as chitosan coated liposomes, ganglioside containing liposomes and PEG coated liposomal preparations that are also designed for oral liposome delivery.

Tagged with: • • • •
Oct 27

A needle free vaccine for tuberculosis

Drug delivery, Life Sciences, Vaccines 1 Comment »

Patent Title- Particulate compositions for pulmonary delivery

Inventors and Affiliation – Batycky; Richard P. (Newton, MA), Edwards; David A. (Boston, MA), Lipp; Michael M. (Framingham, MA)

Key Words- Spray-dried, vaccine, pulmonary, powder, inhaler

The main focus of the patent

This patent describes a method to make pharmaceuticals and vaccines that were previously only administered by injection available by inhalation.  Specifically, the patent describes a method for creating hollow, collapsible drug micron size particles whose properties make them suitable for administration by inhalation.

Limited technical details

Physiochemical properties such as particle size, morphology, electrostatic charge interactions and moisture content are known to influence the overall stability, efficiency and delivery of dry particles used in inhalation therapies. The patents by Edwards et al. (U.S. Pat. No. 7,384,649 and 7182961) identify and list specific properties of particles that render them easily dispersible (mass median diameter of at least about 5 microns, surface area parameter greater than 2, tap density of less than 0.4 g/cm3, a median geometric diameter greater than 5 μm, and an external surface area greater than about 5 m2/g and being able to efficiently penetrate into the lungs when dispensed from a dry powder inhaler. The spray drying method described in the patent creates dry powder pharmaceutical compositions containing the active drug and the vehicle that are hollow, spherical collapsible particles having the above mentioned properties. The patent also goes on to describe specific spray drying conditions required to minimize the average wall thickness of the shells of these particles to less than 150 nanometers, a way to measure and collect particles having the required minimized average wall thickness and finally a method to administer them to the respiratory tract of a patient in need of the drug.

Implications/applications and sectors that are addressed by patent/technology

The patent can potentially have widespread applications in any of the forms inhalation therapy using metered-dose inhalers and nebulizers examples include, beta 2 receptor agonists (used in asthma), corticosteroids, antivirals, antibiotics, and cromolyn (used for preventing symptoms of asthma), the area which the inventors are immediately focusing  is its application to vaccines, which are traditionally administered by injection, but could be administered by inhalation.  Vaccines given by inhalation There are ongoing clinical trials using a spray dried form of the commonly used injectible Bacille Calmette Guerin  (BCG) tuberculosis vaccine as an aerosol.

Inhaled (Needle-free) vaccinations through mucosal surfaces such as nasal passages and lungs are not currently widespread but could represent an emerging market. These vaccines can potentially address shortcomings of conventional injection vaccines such as low acceptance rates (by virtue of being relatively easier and pain-free) and additionally avoid the problems of needle stick injury and contamination as well as the need for trained personnel. Another advantage that a spray dried powder formulation created by this technology can offer is stability at room temperature which would remove the need for refrigeration during storage and transport, a major barrier in developing countries where vaccines for diseases such as tuberculosis are used.  Early studies using the spray dried form of the BCG vaccine have demonstrated to be more effective in animal models than an injectable version

Market: In the specific instance of the tuberculosis vaccine, the worldwide incidence of the disease is about 8 million. However the main market is in the developing countries, especially Asia and sub Saharan Africa where immunization is still a major tool for preventing the disease. In the US, the BCG is not recommended as a means to control TB because of the unproven efficacy of the vaccine in its current form thereby making the development of a more effective alternative an attractive option.

History of the Inventors:

David Edwards, a biomedical engineering professor at Harvard University, he founded Advanced Inhalation Research, Inc., a company that made inhaled form of drugs such as growth hormone and epinephrine and was acquired by Alkermes in 1999. He also co-founded a company called Pulmatrix in 2003 which focuses on respiratory infectious disease. Their products inhibit the formation and transport of infectious aerosols within the lungs thereby decreasing both disease severity as well as spread. Both companies were funded and backed by Polaris Venture Partners.

For the current patent, Edwards, through an international nonprofit he established called Medicine in Need, or MEND has moved the first inhalable TB vaccine candidate into the clinical trial stage.

Richard P. Batycky  was the Vice President, Pulmonary Research and Development at Alkermes , Inc. and is currently the Chief Scientific Officer and Senior Vice President of Research and Development at Pulmatrix Inc.

Michael Lipp was the Director of Formulation Development at Alkermes , Inc.  and is currently Senior Director of Development at Pulmatrix Inc.

Similar patents

US Patent 6635283 – Aerodynamically light particles for pulmonary drug delivery

US Patent 6582728 – Spray drying of macromolecules to produce inhaleable dry powders

US Patent 7541022 – Pharmaceutical formulations for dry powder inhalers

Tagged with: • • • • •
preload preload preload