Thermosensitive injectable hydrogel for drug delivery

• US 9,364,545 B2
• Filed: 06/19/2014
• Issued: 06/14/2016
• Est. Priority Date: 06/19/2014
• Status: Active Grant

• Current Assignee: Taipei Medical University WAN Fan Hospital (Government of The Republic of China)
• Original Assignee: Taipei Medical University WAN Fan Hospital (Government of The Republic of China)
• Inventors: Jhan, Hua-Jing, Ho, Hsiu-O, Sheu, Ming-Thau, Shen, Shing Chuan, Ho, Yuan Soon, Liu, Jun-Jen
• Primary Examiner(s): BERRY, LAYLA D
• Application Number:
  US14/309,266
• Publication Number:
  US 20150366975A1
• Time in Patent Office: 726 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00

Abstract

The invention develops a developed a thermosensitive injectable hydrogel based on HA and a copolymer of polyethylene oxide (PEO) and polypropylene oxide (PPO), which has a gel formation temperature from 30° C. to 37° C. The thermosensitive injectable hydrogel of the invention provides a potential drug delivery system that can increase therapeutic efficacy of the drug.

Claims

1. A thermosensitive injectable hydrogel, which has a gel formation temperature from 30°

C. to 37°

C. and comprises an HA polymer and a copolymer of polyethylene oxide (PEO) and polypropylene oxide (PPO), wherein the amounts of HA and the polymer are about 0.01% (w/v) to about 0.2% (w/v) and about 15% (w/v) to about 18% (w/v), respectively;

wherein HA has a mean molecular weight of about 1,500,000 Da to about 2,500,000 Da.

2. The thermosensitive injectable hydrogel of claim 1, wherein HA has a mean molecular weight of 1,500,000 Da to about 2,200,000 Da.

3. The thermosensitive injectable hydrogel of claim 1, wherein the copolymer of PEO and PPO is poly(ethylene oxide-propylene oxide-ethylene oxide) (PEO-PPO-PEO).

4. The thermosensitive injectable hydrogel of claim 1, wherein the copolymer of PEO and PPO is Pluronic F68NF, Pluronic F127NF, Pluronic F108NF, Pluronic F38NF, or Pluronic F87NF.

5. The thermosensitive injectable hydrogel of claim 1, wherein the copolymer of PEO and PPO is Pluronic F127NF.

6. The thermosensitive injectable hydrogel of claim 1, which comprises about 0.01% to about 0.15% (w/v) HA and about 15% to about 17.5% (w/v) copolymer of PEO and PPO.

7. A method of using the thermosensitive injectable hydrogel of claim 1 comprising the step of administrating the thermosensitive injectable hydrogel to a subject, wherein the step is selected from the group consisting of:

intratumoral injection, subcutaneous injection, oral delivery, ocular delivery, transdermal, ophthalmic, wound healing, Intraperitoneal injection, gene delivery, tissue engineering, colon specific drug delivery.

8. A drug delivery system, comprising a thermosensitive injectable hydrogel of claim 1 and an active agent.

9. The drug delivery system of claim 8, wherein the delivery is intratumoral injection, subcutaneous injection, oral delivery, ocular delivery, transdermal delivery, ophthalmic delivery, topical delivery, intraperitoneal injection, gene delivery or colon specific drug delivery.

10. The drug delivery system of claim 8, wherein the active agent is an anticancer drug, a radionuclide, a gene therapy composition, a hormone, a nutriceutical, an antibiotic, an anti-inflammatory agent, an anti-viral agent, a wound healing agent, an antibacterial agent or a combination thereof.

11. The drug delivery system of claim 10, wherein the anticancer drug is methotrexate, carboplatin, taxol, cisplatin, 5-fluorouracil, doxorubicin, etpocide, paclitaxel, camtotecin, cytosine, arabinose, docetaxel or a mixture thereof.

12. A method for treating or alleviating one or more symptoms of a disease in a subject, comprising administering to a subject in need thereof a drug delivery system of claim 8.

13. The method of claim 12, wherein the administration is intratumoral injection, subcutaneous injection, oral delivery, ocular delivery, transdermal, ophthalmic, topical delivery, intraperitoneal injection, gene delivery or colon specific drug delivery.

14. The method of claim 12, wherein the disease is a cancer.

15. The method of claim 12, wherein the drug delivery system comprises an anti-cancer drug.

16. The method of claim 15, wherein the anti-cancer drug is doxorubicin or docetaxel.