Nano technologies -
Biodegradable MicroSpheres for Drug and Vaccine
Delivery
Introduction
Immunizations are an essential tool
in the prevention of many infectious diseases. DNA vaccines
offer great promise for safer and more effective vaccines
when compared to traditional protein immunizations.
Current technologies for the delivery of DNA vaccines
involve the simple injection of DNA in solutions, use
of cationic polymers or lipids, or use of gene guns.
Efficient, targeted delivery of nucleic acids to antigen
processing cells could significantly enhance the efficacy
of nucleic acid based immunotherapy for cancer and infectious
diseases. Nucleic acids, surface adsorbed on cationic
particles, have been shown to produce superior immune
responses compared to existing methods. Currently, such
cationic particles are synthesized by non-covalent incorporation
of cationic polymers or surfactants on the surface of
polymer micro-particles, which suffer from easy and
premature dissociation of the cationic polymer and nucleic
acids. In addition, cationic surfactants are often toxic
and do not possess any intrinsic mechanism to enhance
DNA delivery inside the cells. Improved non-toxic formulations,
with built-in properties for enhancing gene transfer
efficacy, are therefore needed for successful clinical
translation of nucleic acid based immunotherapy.
Invention Description
This patent overcomes the limitations
of non-covalent adsorption and cationic surfactants
through the covalent conjugation of branched polyamines
and biodegradable polymer particle surfaces to produce
cationic microparticles for nucleic acid loading. Secondly,
this technology allows for surface conjugation of transfection
enhancing polyamines with intrinsic endosomal buffering
ability, which could lead to a more efficient delivery
vehicle for nucleic acid vaccines and immunotherapy.
Thirdly, this technology has the ability to co-deliver
multiple types of nucleic acids (DNA, RNA and oligos)
as well as peptides and proteins in the same vehicle.
One or more molecules on the surface and other molecules
encapsulated inside the particles ensure that multiple
drugs are delivered efficiently to the same cells.
Benefits
Enhanced nucleic acid delivery
Reduced toxicity
Better phagosomal escape properties
important in nucleic acid transfer
Multi-agent delivery in the same
vehicle and to the same cell
Appropriate immune modulation is
easily achieved
Features
Covalent conjugation of branched or
linear polyamines and PLGA particle surfaces to produce
cationic microparticles for nucleic acid loading
The ability to impart phagosomal escape
properties to biodegradable micro-particles
Co-delivery of multiple types of nucleic
acids (DNA, RNA and oligos) as well as peptides and
proteins in the same vehicle
Market Potential/Applications
This technology could be used to improve
vaccines for BSE/ Cholera, Hepatitis B/C, Herpes simplex
virus, HIV, Influenza, Malaria, Papilloma virus, Rabies,
Tuberculosis as well as others. Also, DNA vaccines may
be used to elicit a protective or therapeutic immune
response against cancer. Using oligonulcetides or SiRNA,
these vehicles can also be used for antisense and silencing
gene therapy applications. Finally, this technology
can be used for topical drug delivery applications.
IP Status
One U.S. Patent Application filed
UT Researcher
Krishnendu Roy, Ph. D., Department
of Biomedical Engineering, The University of Texas at
Austin
OTC Contact Information
Robert Schatz, Licensing Specialist
rschatz@otc.utexas.edu
512-475-7659