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Electrostatically Mediated Liposome Fusion and Lipid Exchange with a Nanoparticle-Supported Bilayer for Control of Surface Charge, Drug Containment, and Delivery

Details

Project TitleElectrostatically Mediated Liposome Fusion and Lipid Exchange with a Nanoparticle-Supported Bilayer for Control of Surface Charge, Drug Containment, and Delivery
Track Code2010-028
Short Description

A novel method where successive steps of electrostatistically mediated lipid exchange between silica-supported layers and oppositely charged free liposomes reduces bilayer defects and controls surface charge, allowing cargo retention, delivery and release inside cells.

Abstract

Drug loaded cationic silica cores were fused and successively exchanged with liposomes of opposite charges. The researchers used lipid fusion and exchange between free and nanoparticle-supported liposomes to reduce defects and control the zeta potential (surface charge) of protocells. These parameters are crucial for drug containment and delivery to mammalian cells.

 
Tagsdiagnostic, drug delivery, imaging agents
 
Posted DateApr 5, 2013

Researcher

Name
C. Brinker
Juewen Liu
Xingmao Jiang
Carlee Ashley
Eric Carnes
David Peabody
Walker (Kip) Wharton
Bryce Chackerian
Cheryl Willman

Manager

Name
Jovan Heusser

Background

Targeted delivery of drugs encapsulated within nanocarriers can potentially improve a number of problems exhibited by conventional `free` drugs, including poor solubility, limited stability, rapid clearing, and, in particular, lack of selectivity, which results in non-specific toxicity to normal cells and prevents the dose escalation necessary to eradicate diseased cells. The major challenge for liposomes and other targeted nanocarriers is to simultaneously achieve high targeting specificity and delivery efficiency, while avoiding non-specific binding and entrapment by the body's defenses. Mesoporous silica nanoparticles are very attractive because of their biocompatibility combined with high surface area and pore volume as well as uniform, tunable pore diameters and surface chemistries. Recently, such porous silica particles have been utilized to deliver a wide range of drugs and therapeutic agents, including chemotherapy drugs, proteins, and DNA. Achieving high drug loading, however, is only one facet of the drug delivery problem. It is equally important that loaded drugs are retained and protected before reaching target tissues or cells to maximize drug efficacy and minimize toxicity. For drugs loaded by electrostatic interactions or physical adsorption in freely accessible pores, metabolites/ions in the body fluid can displace the drugs resulting in premature drug release. To avoid this, molecular-gating strategies based on coumarin, azobenzenes, rotaxanes, polymers, and nanoparticles have been designed, wherein drugs are released only upon gate opening or removal.

Technology Description

Researchers at the University of New Mexico have developed a novel method where successive steps of electrostatistically mediated lipid exchange between silica-supported layers and oppositely charged free liposomes reduces bilayer defects and controls surface charge, allowing cargo retention, delivery and release inside cells. Drug loaded cationic silica cores were fused and successively exchanged with liposomes of opposite charges. The researchers used lipid fusion and exchange between free and nanoparticle-supported liposomes to reduce defects and control the zeta potential (surface charge) of protocells. These parameters are crucial for drug containment and delivery to mammalian cells.

This technology builds on the silica-nanostructure technology platform (2009-054) that is made of a porous inorganic particle/ nanoparticle core and a lipid bilayer shell to form a ‘protocell’ that can be useful for a wide range of applications.

Advantages/Applications

  • Reduces bilayer defects
  • Controls surface charge
  • Endocytosis based cellular intake rather than nonspecific intake protocells
  • Targeted and controlled release of drug inside the cells in high concentration
  • Avoids premature drug release, thereby significantly reducing drug toxicity
  • Modified protocells yielded >98% cell viability, which also contributes to reduced drug toxicity
  • Liposome coating is amenable to molecular modifications such as inclusion of receptor proteins, antibodies for further specific targeting etc.

Applications:

  • Drug delivery
  • Diagnostics
  • Imaging agents
  • Disease treatment
  • Anti-infectious applications
  • Targeted drug delivery to organs or cells

Publications

INQUIRES

STC has filed intellectual property on this exciting new technology and is currently exploring commercialization options. If you are interested in information about this or other technologies, please contact Arlene Mirabal at amirabal@stc.unm.edu or 505-272-7886.

Files

File Name Description
9,480,653 Issued Patent None Download
8,992,984 Issued Patent None Download

Intellectual Property

Patent Number Issue Date Type Country of Filing
9,480,653 Nov 1, 2016 Divisional United States
8,992,984 Mar 31, 2015 Utility United States