IP Library Granted Patent US 10,201,499
Granted Patent B2
US 10,201,499 · App. 14/424,332 · Granted Feb 12, 2019

Nanoparticle formulation

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Quick Facts
Patent No.
US 10,201,499
App. No.
14/424,332
Granted
Feb 12, 2019
Kind
B2
Abstract

The present invention concerns nanoparticle formulations suitable for the delivery of one or more therapeutic agents, the formulations comprising: a cationic cholesterol derivative; a neutral phospholipid; cholesterol or a neutral cholesterol derivative; and a saturated fatty acid, PEGylated neutral derivative of phosphatidylethanolamine or phosphatidylcholine.

Claims (27)

1. A cationic liposomal nanoparticle for the delivery of one or more short-chain fatty acid therapeutic agents consisting of:

i) a cationic cholesterol derivative;

ii) a neutral phospholipid;

iii) cholesterol or a neutral cholesterol derivative;

iv) a neutral saturated fatty acid derivative of phosphatidylethanolamine or phosphatidylcholine, which derivative is PEGylated; and

v) a therapeutic agent consisting of a short-chain fatty acid;

vi) optionally aqueous 4-2-(hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer;

vii) optionally NaCI;

viii) optionally a tumour targeting agent;

ix) optionally a fluorescent phospholipid;

x) optionally one or more lipids for improving magnetic resonance imaging or nuclear magnetic resonance imaging;

wherein the short chain fatty acid therapeutic agent is encapsulated within the nanoparticle.

2. The nanoparticle according to claim 1 , wherein the short-claim fatty acid is selected from the group consisting of acetic acid, propionic acid, and butyric acid.

3. The nanoparticle according to claim 2 , wherein the short-chain fatty acid is acetic acid.

4. The nanoparticle according to claim 1 , sized in the range of 1to 500 nm or 40-120 nm.

5. The nanoparticle according to claim 1 , wherein the concentration of encapsulated therapeutic agent is in the range of 0.1 to 20mM or wherein the concentration of encapsulated therapeutic agent is in the range of 1 to 10 mM.

6. The nanoparticle according to claim 1 , wherein the cationic cholesterol derivative is a cholesterol derivative having a polyamine hydrocarbon appendage wherein the polyamine appendage is optionally of the formula: H 2 N(CH 2 ) x NH(CH 2 ) y NH(CH 2 ) z NHC(O)—, wherein x is 1 to 10, y is 1 to 10, and z is 1 to 10.

7. The nanoparticle according to claim 1 , wherein the neutral phospholipid is a saturated neutral phospholipid or wherein the neutral phospholipid is a phosphatidylcholine or phosphatidylethanolamine phospholipid.

8. The nanoparticle according to claim 1 , wherein the neutral saturated fatty acid derivative of phosphatidylethanolamine or phosphatidylcholine, which derivative is PEGylated, comprises saturated fatty acid chains of C 12 -20 or has a polyethylene glycol chain with a molecular weight of at least 100 or at least 1000.

9. The nanoparticle according to claim 1 , wherein the molar ratio range of elements (i) to (iv) satisfies the following ranges:

(i) 20 to 40;

(ii) 20 to 40;

(iii) 25 to 55; and

(iv) 1 to 10, respectively.

10. The nanoparticle according to claim 1 , wherein the tumour targeting agent is present and is a ligand for a receptor that is overexpressed in tumour cells relative to the expression of said receptors in the cells of non-tumourous tissue of mammals.

11. The nanoparticle according to claim 10 , wherein the tumour targeting agent has a folate moiety, or wherein the tumour targeting agent is a phospholipid-polyethylene glycol-folate compound or tumour targeting agent is DSPE-PEG(2000)—Folate [distearoylphosphatidylethanolamine-polyethylene glycol (2000)—folate].

12. The nanoparticle according to claim 11 , wherein the amount of the folate moiety present in the formulation is 1-2mol % of the total formulation.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 11, 2018
From: IMPERIAL INNOVATIONS LIMITED
To: MEDICAL RESEARCH COUNCIL
Reel/Frame 047740/0956 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 2, 2018
From: MEDICAL RESEARCH COUNCIL
To: UNITED KINGDOM RESEARCH AND INNOVATION
Reel/Frame 046469/0108 →
ASSIGNMENT OF JOINT UNDIVIDED RIGHT, TITLE AND INTEREST Recorded Jul 7, 2015
From: BRODY, LEIGH; ARISOYLU, MELIZ SAHURI; FROST, GARY
To: IMPERIAL INNOVATIONS LTD
Reel/Frame 036074/0504 →
ASSIGNMENT OF JOINT UNDIVIDED RIGHT, TITLE AND INTEREST Recorded Jul 7, 2015
From: BELL, JIMMY; THOMAS, ELIZABETH LOUISE; MILLER, ANDREW
To: MEDICAL RESEARCH COUNCIL
Reel/Frame 036074/0552 →
Cited By (2)
US 12,559,450 US 12,605,464