Application of lipid vehicles and use for drug delivery

• US 7,063,860 B2
• Filed: 08/13/2002
• Issued: 06/20/2006
• Est. Priority Date: 08/13/2001
• Status: Active Grant

• Current Assignee: University Of Pittsburgh (University of Pittsburgh of The Commonwealth System of Higher Education)
• Original Assignee: University Of Pittsburgh (University of Pittsburgh of The Commonwealth System of Higher Education)
• Inventors: de Groat, William C., Fraser, Matthew O., Chancellor, Michael B., Huang, Leaf, Yoshimura, Naoki, Chuang, Yao-Chi
• Primary Examiner(s): Kishore, Gollamudi S.
• Application Number:
  US10/218,797
• Publication Number:
  US 20030108597A1
• Time in Patent Office: 1,407 Days
• Field of Search: 424/450, 424434-435, 424/443, 424/45, 514/937, 514/943
• US Class Current: 424/450
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention relates to compositions and methods for the administration of lipid-based vehicles to treat various disorders, including bladder inflammation, infection, dysfunction, and cancer. In various aspects, the compositions and methods of the invention are useful for prolonged delivery of drugs, e.g., antibiotics, pain treatments, and anticancer agents, to the bladder, genitourinary tract, gastrointestinal system, pulmonary system, and other organs or body systems. In particular, the present invention relates to liposome-based delivery of vanilloid compounds, such as resiniferatoxin, capsaicin, or tinyatoxin, and toxins, such as botulinum toxin, for the treatment of bladder conditions, including pain, inflammation, incontinence, and voiding dysfunction. Further related are methods of using these vehicles alone or in conjunction with antibodies, e.g., uroplakin antibodies, to improve duration of liposome attachment, and provide a long-term intravesical drug delivery platform. The present invention specifically relates to antibody-coated liposomes that are useful for targeting specific receptors for drug, peptide, polypeptide, or nucleic acid delivery. In one particular aspect, the present invention relates to liposomes coated with antibodies against nerve growth factor (NGF) receptor and containing NGF antisense nucleic acids, which are used as a treatment for neurogenic bladder dysfunction.

Claims

1. A method of treating bladder conditions comprising administering via intravesical instillation to a mammalian subject in need thereof an effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises:

a) an empty, non-ionic phospholipid liposome; and

b) a physiologically acceptable carrier, excipient, or diluent.

2. The method of claim 1, wherein the nonionic phospholipid of the liposome is derived from egg yolk.

3. The method of claim 1, wherein the bladder condition is associated with a medical condition selected from the group consisting of anxiety, aging, infection, diabetes mellitus, brain tumor, spinal cord tumor, spinal cord injury, stroke, ruptured intervertebral disk, demyelinating disease, degenerative disease of the nervous system, irritation, inflammation, micturition pattern alteration, and incontinence.

4. The method of claim 1, wherein the carrier, excipient, or diluent comprises physiological saline.