Lipidated glycoprotein particles and methods of use

Patent metadata

Field	Value
Publication number	US-2016354318-A1
Application number	US-201615228449-A
Country	US
Kind code	A1
Filing date	Aug 4, 2016
Priority date	Jul 13, 2004
Publication date	Dec 8, 2016
Grant date	—

Abstract

Lipidated micro- or macroparticles are prepared by covalently linking a glycoprotein, typically collagen, with at least one lipid. An amino group in the glycoprotein is joined with a primary amine in the lipid. These particles can be used to encapsulate active ingredients, such as drugs.

First claim

1 . Lipidated glycoprotein microparticles or macroparticles comprising the reaction product of at least one amino-containing glycoprotein with at least one lipid having a primary amino group.

2 . The lipidated glycoprotein microparticles or macroparticles of claim 1 , wherein the lipid is phosphatidylethanolamine.

3 . The lipidated glycoprotein microparticles or macroparticles of claim 1 , wherein the glycoprotein is collagen.

4 . The lipidated glycoprotein microparticles or macroparticles of claim 1 , consisting of microparticles ranging in size from about 0.5 to about 10 microns in diameter.

5 . The lipidated glycoprotein microparticles or macroparticles of claim 1 , wherein a drug or other biologically active ingredient is encapsulated within the microparticles or macroparticles.

6 . The lipidated glycoprotein microparticles or macroparticles of claim 5 , wherein the drug or other biologically active ingredient is selected from the group consisting of anti-infective agents, anti-neoplastic drugs, anti-fungal agents, anti-viral agents, anti-microbial drugs, chemotherapeutic agents, anti-inflammatory agents, anti-psychotics, vaccines, fluorescent dyes, proteins, hormones, enzymes, cells, and nucleic acids.

7 . The lipidated glycoprotein microparticles or macroparticles of claim 1 , consisting of macroparticles ranging in size from about 1 mm to about 20 mm in diameter.

8 - 9 . (canceled)

10 . A method of preparing lipidated glycoprotein macroparticles, comprising the steps of:
(a) dissolving a glycoprotein;
(b) providing a reaction vessel in which a lipid is disposed in a thin layer;
(c) buffering the lipid to a basic pH;
(d) admixing the dissolved glycoprotein in the reaction vessel;
(e) adding a crosslinker, and optionally adding a bioactive agent stable at a basic pH;
(f) incubating the glycoprotein and lipid and cross-linker reaction mixture, with continuous shaking, for an amount of time and under temperature conditions sufficient for lipidated glycoprotein disks to form; (g) buffering a resultant lipidated glycoprotein disk to a neutral pH; (h) separating unbound glycoprotein by centrifugation; and (i) lyophilizing the resultant lipidated glycoprotein disk to produce lipidated glycoprotein microparticles.

11 . The method of claim 10 , wherein the lipid is phosphatidylethanolamine.

12 . The method of claim 10 , wherein the glycoprotein is collagen.

13 - 16 . (canceled)

17 . The method of claim 10 , wherein the lipidated glycoprotein disks have a biologically active ingredient entrapped therein, and wherein the lyophilized glycoprotein disks are reconstituted in water, and a powdered biologically active ingredient is added, whereby the active ingredient is entrapped within the lipidated glycoprotein disks.

18 . (canceled)

19 . A method for treating an animal suffering from a pathological condition, comprising administering to the animal in need thereof an effective amount of the lipidated glycoprotein microparticles or macroparticles of claim 5 , wherein the pathological condition is selected from the group consisting of cancer, bacterial infections, fungal infections, viral infections, parasite infections, prion infections, osteoarthritis, and osteomyelitis.

20 - 26 . (canceled)

27 . A method in accordance with claim 19 , wherein the pathological condition is osteoarthritis and the bioactive agent is a anti-inflammatory agent suitable for treating osteoarthritis.

28 . A method of diagnostic imaging of cancer cells in a patient, comprising:
administering the lipidated glycoprotein microparticles or macroparticles of claim 1 encapsulating a marker used in imaging, and imaging to detect the presence of cancer cells in the patient.

29 . The method according to claim 28 , wherein the marker is a radioactive isotope.

30 . The method according to claim 29 , wherein the radioactive isotope is selected from the group consisting of 99mTc, 127I, and 67Gd.

31 . The method according to claim 30 , wherein the marker is a fluorescent molecule.

32 . In a method of diagnostic imaging of cancer cells, comprising the steps of administering a diagnostic agent to a patient and imaging the patient to detect the presence and/or location of the diagnostic agent, the improvement wherein the diagnostic agent is lipidated glycoprotein microparticles or macroparticles in accordance with claim 5 .

33 . In a method of gene delivery and short-term expression of nucleic acids to cancer cells for therapeutic purposes, comprising administering to an animal in need thereof an effective amount of nucleic acids, the improvement wherein the nucleic acids are formulated so as to be encapsulated in the lipidated glycoprotein microparticles or macroparticles in accordance with claim 1 .

34 . In a method for treating an indication with a drug that is effective for treating said indication, the improvement wherein said drug is administered encapsulated in lipidated glycoprotein microparticles or macroparticles.

35 - 36 . (canceled)

Assignees

• Ramot At Tel-Aviv Univ Ltd

Inventors

• Margalit Rimona
• Peer Dan

Classifications

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61K9/1658

  Proteins, e.g. albumin, gelatin · CPC title

• A61K9/5052 Primary

  Proteins, e.g. albumin · CPC title

• A61K31/14

  Quaternary ammonium compounds, e.g. edrophonium, choline (betaines A61K31/205) · CPC title

• A61K31/165

  having aromatic rings, e.g. colchicine, atenolol, progabide · CPC title