Temperature-sensitive polymer/nanoshell composites for photothermally modulated drug delivery

• US 6,428,811 B1
• Filed: 07/14/2000
• Issued: 08/06/2002
• Est. Priority Date: 03/11/1998
• Status: Expired due to Term

• Current Assignee: Rice University
• Original Assignee: Rice University
• Inventors: Halas, Nancy J., West, Jennifer L., Sershen, Scott R., Oldenburg, Steven J., Averitt, Richard D.
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US09/616,127
• Time in Patent Office: 753 Days
• Field of Search: 424/490, 424/497, 428/403
• US Class Current: 424/497
• CPC Class Codes: A61K 41/0028 Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
• CPC Class Codes: A61K 41/0042 Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
• CPC Class Codes: A61K 47/6903 the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
• CPC Class Codes: A61K 47/6923 the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50
• CPC Class Codes: B22F 1/054 Nanosized particles
• CPC Class Codes: B22F 1/18 Non-metallic particles coated with metal
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C01P 2002/82 by IR- or Raman-data
• CPC Class Codes: C01P 2002/84 by UV- or VIS- data
• CPC Class Codes: C01P 2004/04 obtained by TEM, STEM, STM or AFM
• CPC Class Codes: C01P 2004/12 with a cylindrical shape
• CPC Class Codes: C01P 2004/32 Spheres
• CPC Class Codes: C01P 2004/38 cube-like
• CPC Class Codes: C01P 2004/50 Agglomerated particles
• CPC Class Codes: C01P 2004/54 Particles characterised by their aspect ratio, i.e. the ratio of sizes in the longest to the shortest dimension
• CPC Class Codes: C01P 2004/61 Micrometer sized, i.e. from 1-100 micrometer
• CPC Class Codes: C01P 2004/62 Submicrometer sized, i.e. from 0.1-1 micrometer
• CPC Class Codes: C01P 2004/64 : Nanometer sized, i.e. from 1-100 nanometer
• CPC Class Codes: C01P 2004/80 : Particles consisting of a mixture of two or more inorganic phases
• CPC Class Codes: C01P 2006/22 : Rheological behaviour as dispersion, e.g. viscosity, sedimentation stability
• CPC Class Codes: C01P 2006/33 : Phase transition temperatures
• CPC Class Codes: C01P 2006/40 : Electric properties
• CPC Class Codes: C01P 2006/60 : Optical properties, e.g. expressed in CIELAB-values
• CPC Class Codes: C08K 9/02 : Ingredients treated with inorganic substances
• CPC Class Codes: C09C 1/3054 : Coating
• CPC Class Codes: C09C 1/3081 : Treatment with organo-silicon compounds
• CPC Class Codes: C09C 1/309 : Combinations of treatments provided for in groups C09C1/3009 - C09C1/3081
• CPC Class Codes: C09K 3/00 : Materials not provided for elsewhere
• CPC Class Codes: G01N 21/658 : enhancement Raman, e.g. surface plasmons
• CPC Class Codes: G02F 1/355 : characterised by the materials used
• CPC Class Codes: G21K 1/10 : Scattering devices; Absorbing devices; Ionising radiation filters
• CPC Class Codes: Y10T 428/2991 : Coated

Abstract

A thermally sensitive polymer-particle composite that absorbs electromagnetic radiation, and uses the absorbed energy to trigger the delivery of a chemical is disclosed. Metal nanoshells are nanoparticulate materials that are suitable for use in the present composites and can be made according to a process that includes optically tuning or tailoring their maximum optical absorption to any desired wavelength primarily by altering the ratio of the core diameter to the shell thickness. Preferred nanoshells are selected that strongly absorb light in the near-infrared and thus produce heat. These nanoshells are combined with a temperature-sensitive material to provide an implantable or injectable material for modulated drug delivery via external exposure to near-IR light. This invention provides a means to improve the quality of life for persons requiring multiple injections of a drug, such as diabetes mellitus patients.

Claims

1. A composition for modulated delivery of a chemical to a desired location, said composition comprising:

a plurality of optically heatable particles capable of converting incident radiation into heat energy when said particles are irradiated with electromagnetic radiation; and

a medium, said medium containing the chemical and comprising a thermally responsive material in thermal contact with said particles.

2. The composition according to claim 1 wherein said particles each comprise:

a non-conducting core,

a metal shell adhering to said core and,

a defined core radius;

shell thickness ratio,

optionally, a molecular linkage between said shell and said core, and

said particles having a defined wavelength absorbance maximum when said particle is irradiated with electromagnetic radiation.

3. The composition according to claim 2 wherein said core has an independently defined diameter and said shell has an independently defined thickness.

4. The composition of claim 1 wherein said particles have a wavelength absorbance maximum between about 300 nm and about 20 μ

m.

5. The composition of claim 1 wherein said thermally responsive material comprises at least one polymer.

6. The composition of claim 5 wherein said at least one polymer is a copolymer of N-isopropylacrylamide and acrylamide.

7. The composition of claim 1 wherein said medium is a hydrogel.

8. The composition of claim 1 wherein said medium comprises at least two layers.

9. The composition of claim 8 wherein said particles are embedded in at least one said layer.

10. The composition of claim 1 wherein said defined wavelength absorbance maximum is in the near-infrared range of the electromagnetic spectrum.

11. The composition of claim 1 wherein said particles and said thermally responsive medium together form microparticulates.

12. The composition of claim 1 in the form of a desiccated polymer-particle composite capable of forming a hydrogel.

13. The composition of claim 1 further comprising at least one therapeutic agent releasably contained in said medium such that when the temperature of said medium or portion thereof is at a first temperature said agent is retained, and when said medium or a portion thereof is at a second temperature higher than said first temperature, at least a portion of said agent is released from said medium.

14. The composition of claim 13 wherein said first temperature is approximately normal body temperature of said subject and said second temperature is about 1-20°

C. higher than said normal body temperature.

15. The composition of claim 13 wherein said thermally responsive material is substantially solid at said first temperature and undergoes a reversible phase transition above said second temperature.

16. The composition of claim 13 wherein said agent is contained in said thermally responsive medium.

17. A system for modulated in vivo delivery of a therapeutic agent comprising:

an implantable composition containing;

a plurality of optically heatable particles capable of converting incident radiation into heat energy when said particles are irradiated with electromagnetic radiation;

at least one therapeutic agent, and

a medium comprising a thermally responsive material in contact with said particles, said material substantially retaining said agent at a first temperature and substantially releasing said agent at a second temperature that is higher than said first temperature; and

optionally, a biosensor system.