摘要:
Polynucleotide complexes are stabilized by adding a cryoprotectant compound and lyophilizing the resulting formulation. The lyophilized formulations are milled or sieved into a dry powder formulation which may be used to deliver the polynucleotide complex. Delivery of the polynucleotide to a desired cell tissue is accomplished by contacting the tissue with the powder to rehydrate it. In a preferred embodiment, a dry powder formulation is used to transfer genetic information to the cells of the respiratory tract.
摘要:
The invention comprises stabilized polynucleotide complexes that have a cryoprotectant and are lyophilized. Cryoprotectant compounds comprise carbohydrates or sugars, preferably lactose and sucrose, but also glucose, maltodextrins, mannitol, sorbitol, trehalose, and others. Other suitable cryoprotectants include amino acids such as betaines and prolines. Polynucleotide complexes stabilized according to the invention can be used for transfection, and exhibit improved tranfection efficiency with respect to polynucleotide complexes without cryoprotection.
摘要:
The invention separates defined, active complexes by a characteristic from Defined, active complexes that share a particular physicochemical characteristic such as density, surface charge or particle size are separated from complexes formed by the association of a polynucleotide with a transfecting component that increases transfection activity, such as a lipid, cationic lipid, liposome, peptide, cationic peptide, dendrimer or polycation. In a preferred embodiment, polynucleotide-transfecting component complexes are ultracentrifuged to resolve one or more bands corresponding to complexes having a specific polynucleotide-transfecting component interaction. Polynucleotide complexes having a cationic liposome transfecting component resolve into two primary bands corresponding to complexes formed either under excess lipid conditions or under excess polynucleotide conditions. In an alternate embodiment, polynucleotide-transfecting component complexes are resolved using cross-flow electrophoresis to identify complexes having specific interactions and to separate them from excess initial components.
摘要:
In various embodiments, the present invention provides zwitterionic lipids, encapsulants incorporating these zwitterionic lipids and such encapsulants encapsulating one or more bioactive agent. An exemplary bioactive agent is a nucleic acid. Also provided are pharmaceutical formulations of the encapsulants and methods of using such formulations to deliver a bioactive agent to a subject in treating or diagnosing disease in that subject.
摘要:
The invention comprises lipid derivatives that rapidly degrade in the pH range from 4.0 to 7.0 and lipidic delivery systems that contain them. These lipid derivatives can be used to modify the delivery properties of the lipidic delivery systems to enable prolonged circulation times or more rapid drug unloading in the target tissue. The lipid derivatives are amphipathic compounds comprising a hydrophilic head group joined to a hydrophobic group by an acid-labile ortho ester linkage. The delivery systems of the invention exhibit degradation of less than 10% within 3 hours at a pH of 7.4 and degradation greater than 50% within 60 min at a pH of 5.0.
摘要:
The present invention relates to liposomal vaccine compositions, methods for the manufacture thereof, and methods for the use thereof to stimulate an immune response in an animal. These compositions comprise dimyristoylphosphatidylcholine (“DMPC”); either dimyristoylphosphatidylglycerol (“DMPG”) or dimyristoyltrimethylammonium propane (“DMTAP”) or both DMPC and DMTAP; and at least one sterol derivative providing a covalent anchor for one or more immunogenic polypeptide(s) or carbohydrate(s).
摘要:
This invention provides a self-assembling polynucleotide delivery system comprising components aiding in the delivery of the polynucleotide to the desired address which are associated via noncovalent interactions with the polynucleotide. The components of this system include DNA-masking components, cell recognition components, charge-neutralization and membrane-permeabilization components, and subcellular localization components. Specific compounds useful in this system are also provided.
摘要:
A self-assembling polynucleotide delivery system comprises a dendrimer polycation aiding in the delivery of the polynucleotide to a desired address, and optionally other agents such as DNA masking agents, cell recognition agents, charge-neutralization agents, membrane-permeabilization agents, and subcellular-localization agents.
摘要:
A self-assembling polynucleotide delivery system comprises a dendrimer polycation aiding in the delivery of the polynucleotide to a desired address, and optionally other agents such as DNA masking agents, cell recognition agents, charge-neutralization agents, membrane-permeabilization agents, and subcellular-localization agents.
摘要:
The invention is a drug delivery system of a delivery vehicle having a low molecular weight hyaluronan ligand with an affinity for CD44 receptors. Preferably, the delivery vehicle is a liposome but other suitable delivery vehicles include microspheres, micelles, emulsions, lipid discs, polymers, viral particles and viruses. The systems of the invention may further comprise a drug, which can be any anticancer agent or other therapeutic or diagnostic agent. The invention also comprises methods of delivering a drug to a cell that expresses CD44 by contacting the cell with the drug delivery system. Further methods include treating a patient with cancer and targeting drug delivery to cells that express CD44 by attaching a glycosaminoglycan ligand.