Biodegradable MicroSpheres for Drug and Vaccine Delivery
Background 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.
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
Covalent conjugation of branched or linear polyamines and PLGA particle surfaces to produce cationic microparticles for nucleic acid loadingThe ability to impart phagosomal escape properties to biodegradable micro-particlesCo-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., Biomedical Engineering, The University of Texas at Austin Sudhir Pai Kasturi, Biomedical Engineering, The University of Texas at Austin
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