Stabilization and controlled delivery of ionic biopharmaceuticals - Patents

Stabilization and controlled delivery of ionic biopharmaceuticals

Agent: Alan J. Howarth - Sandy, UT, US
Inventors: You Han Bae, Jong Ho Kim, Ajay Taluja
Class: 435458000 (USPTO), C12N015/88 (Intl Class)
#20050118718
06/02/05

Compositions and methods for stabilization and controlled release of ionic biopharmaceuticals are disclosed. Illustrative compositions according to the present invention include polyelectrolyte-PEG diblock copolymers complexed by ionic bonds with the ionic biopharmaceuticals. Additional illustrative compositions include microspheres encapsulating polyelectrolyte-PEG diblock copolymers complexed by ionic bonds with the ionic biopharmaceuticals. A method of delivering a biopharmaceutical to a person in need thereof involves administering microspheres that encapsulate biopharmaceutical/polyelectrolyte-PEG diblock copolymer complexes.
BRIEF SUMMARY OF THE INVENTION
[0020] An illustrative advantage of the present invention comprises providing compositions and methods for the stabilization and storage of biologically active macromolecules, such as proteins and peptides, nucleic acids, and antisense oligonucleotides (ODNs).
[0021] Another advantage is providing for controlled release of biologically active macromolecules, such as proteins and peptides, nucleic acids, and antisense oligonucleotides (ODNs), by encapsulation in suitable formulations and compositions.
[0022] These and other advantages are addressed by providing a composition comprising an ionic complex of (a) a biological macromolecule having a charge, and (b) a polyelectrolyte-poly(ethylene glycol) diblock copolymer having an opposite charge. The polyelectrolyte-poly(ethylene glycol) diblock copolymer comprises either a polycation-poly(ethylene glycol)diblock copolymer or a polyanion-poly(ethylene glycol)diblock copolymer. An illustrative polyelectrolyte-poly(ethylene glycol)diblock copolymer comprises a poly(L-histidine)-poly(ethylene glycol)diblock copolymer.
[0023] Another illustrative embodiment of the invention comprises a composition comprising a microsphere encapsulating an ionic complex of (a) a biological macromolecule having a charge, and (b) a polyelectrolyte-poly(ethylene glycol)diblock copolymer having an opposite charge. The microsphere comprises a biocompatible polymer, such as poly(lactide-co-glycolide) (PLGA).
[0024] Still another illustrative embodiment of the invention comprises a method of stabilizing an ionic macromolecule against inactivation comprising:
[0025] (a) determining the charge of the ionic macromolecule; and
[0026] (b) complexing the ionic macromolecule with a polyelectrolyte-poly(ethylene glycol)diblock copolymer of opposite charge.
[0027] Yet another illustrative embodiment of the invention comprises a method of delivering an ionic macromolecule to an individual in need thereof comprising administering to the individual a pharmaceutically effective amount of a microsphere encapsulating an ionic complex of the ionic macromolecule and a polyelectrolyte-poly(ethylene glycol)diblock copolymer.
[0028] Another illustrative embodiment of the invention comprises a method of increasing transfection efficiency of DNA into mammalian cells, the method comprising:
[0029] (a) forming an ionic complex comprising the DNA and a cationic polyelectrolyte-poly(ethylene glycol)diblock copolymer; and
[0030] (b) incubating the ionic complex with the mammalian cells in the presence of a transfection enhancer such that the ionic complex, and hence the DNA, enters the mammalian cells. An illustrative cationic polyelectrolyte-poly(ethylene glycol)diblock copolymer according to the present invention comprises polyhistidine-poly(ethylene glycol)diblock copolymer, and an illustrative transfection enhancer comprises a cationic lipid.
[0031] Still another illustrative embodiment of the invention comprises a method for increasing efficiency of incorporation of ionic macromolecules into microspheres, the method comprising:
[0032] (a) determining the charge of the ionic macromolecules;
[0033] (b) forming ionic complexes comprising the ionic macromolecules and a polyelectrolyte-poly(ethylene glycol)diblock copolymer of opposite charge; and
[0034] (c) mixing the ionic complexes with a polymer suitable for forming microspheres to form a mixture, and treating the mixture for formation of microspheres. An illustrative polymer suitable for forming microspheres comprises poly(lactide-co-glycolide), and treating the mixture for formation of microspheres can illustratively comprise forming a water-in-oil-in-water emulsion and solvent evaporation.
Complete article is available online.