IP Library Granted Patent US 10,369,230
Granted Patent B2
US 10,369,230 · App. 15/480,817 · Granted Aug 6, 2019

Sustained release of a therapeutic agent from PLA-PEG-PLA nanoparticles for cancer therapy

Inventors: Salam Massadeh (Riyadh, SA); Manal Alaamery (Riyadh, SA)
Assignees: National Guard Health Affairs; King Saud bin Abdulaziz University for Health Sciences; King Abdullah International Medical Research Center
A61K47/6935A61K31/4196A61K47/68A61K47/6937C07K16/32A61K9/5146A61K9/5153
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Quick Facts
Patent No.
US 10,369,230
App. No.
15/480,817
Granted
Aug 6, 2019
Kind
B2
Abstract

A nanoparticle that has a membrane including a polylactide-block-poly(ethylene glycol)-block-polylactide (PLA-PEG-PLA) and a polyvinyl alcohol, a bovine serum albumin contacting the membrane on the outside of the nanoparticle, a targeting group attached to the outside of the nanoparticle, and a breast cancer therapeutic agent that is encapsulated by the membrane. A nanoparticle that consists of a membrane including a polylactide-block-poly(ethylene glycol)-block-polylactide (PLA-PEG-PLA) and a polyvinyl alcohol, a bovine serum albumin contacting the membrane on the outside of the nanoparticle, breast cancer therapeutic agent that is encapsulated by the membrane, and an anti-Her2 antibody attached to the outer surface of the nanoparticle. A range of a number average molecular weight of the PEG block is 800 Da to 3 kDa and a range of a number average molecular weight of each of the PLA blocks is from 1 kDa to 5 kDa.

Claims (25)

1. A nanoparticle having an interior space and a membrane surrounding the interior space,

wherein the interior space contains letrozole that is encapsulated by the membrane, and the membrane comprises;

a polylactide-block-poly(ethylene glycol)-block-polylactide block (PLA-PEG-PLA) copolymer wherein a number average molecular weight range of the PEG block is 800 Da to 3 kDa and a number average molecular weight range of each of the PLA block is from 1 kDa to 5 kDa,

a polyvinyl alcohol polymer,

bovine serum albumin in contact with the outer surface of the membrane, and

anti-Her2 antibody attached to the outer surface of the membrane.

2. The nanoparticle of claim 1 , wherein said nanoparticle provides sustained release of letrozole over a period of 72 hours.

3. The nanoparticle of claim 1 , wherein the nanoparticle comprises 60 to 95 weight percent of the polylactide-block-poly(ethylene glycol)-block-polylactide block (PLA-PEG-PLA) copolymer and 0.5 to 5 weight percent of polyvinyl alcohol polymer relative to the total weight of the nanoparticle.

4. The nanoparticle of claim 1 , wherein the bovine serum albumin is 0.5 to 8 weight percent relative to the total weight of the nanoparticle.

5. The nanoparticle of claim 1 , wherein the nanoparticle has a diameter of 300 nm to 370 nm.

6. The nanoparticle of claim 1 , wherein a rate of release of the breast cancer therapeutic agent is a cumulative percent of 25% to 75% in 24 hours to 96 hours.

7. The nanoparticle of claim 1 , wherein the anti-Her2 antibody is bound to the membrane via a biotin-avidin complex.

8. The nanoparticle of claim 7 , wherein the anti-Her2 antibody is sourced from a rabbit.

9. The nanoparticle of claim 1 , wherein the nanoparticle has a diameter of from 310 nm to 350 nm.

10. The nanoparticle of claim 1 , wherein the anti-Her2 antibody is conjugated to the membrane.

11. The nanoparticle of claim 1 , wherein the breast cancer therapeutic agent consists letrozole.

12. The nanoparticle of claim 1 , wherein the breast cancer therapeutic agent is 0.5 to 10 weight percent relative to the total weight of the nanoparticle.

13. The nanoparticle of claim 1 , wherein the nanoparticle has an internal volume of from 1 picoliter to 1 nanoliter.

14. The nanoparticle of claim 1 , wherein the nanoparticle has a zeta potential of −7 mV to −20 mV.

15. The nanoparticle of claim 1 , wherein the membrane further comprises a diblock copolymer.

16. The nanoparticle of claim 15 , wherein a weight percent of the diblock copolymer relative to the total weight of the nanoparticle is 0.01% to 0.1%.

17. The nanoparticle of claim 15 , wherein the diblock copolymer comprises one hydrophobic block polymer and one hydrophilic block polymer.

18. The nanoparticle of claim 17 , wherein the diblock copolymer comprises at least one hydrophobic polymer block selected from the group consisting of polycaprolactone (PCL), polyvalerolactone (PVL), poly(lactide-co-glycolide) (PLGA), polylactic acid (PLA), polybutyrolactone (PBL), polyglycolide, and polypropiolactone (PPL), and at least one hydrophilic polymer block selected from the group consisting of polyethylene glycol (PEG), hyaluronic acid (HA), and poly-γ-glutamic acid (PGA).

19. The nanoparticle of claim 17 , wherein a number average molecular weight range of the hydrophobic block polymer and the hydrophilic block polymer is from 800 Da to 5 kDa.

20. The nanoparticle of claim 1 , wherein the membrane is prepared by a double emulsion method comprising mixing a first emulsion with a second emulsion, wherein the first emulsion and the second emulsion comprise polyvinyl alcohol as an emulsifying agent.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 6, 2017
From: MASSADEH, SALAM; ALAAMERY, MANAL
To: NATIONAL GUARD HEALTH AFFAIRS; KING SAUD BIN ABDULAZIZ UNIVERSITY FOR HEALTH SCIENCES; KING ABDULLAH INTERNATIONAL MEDICAL RESEARCH CENTER
Reel/Frame 041886/0136 →
Continuity (1)
Related Publication 20180289837A1 · Oct 11, 2018