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

#1. Field of the Invention

#The present invention generally relates to chemical delivery by controlled release from an implanted device or medium. More particularly, the invention relates to composite materials containing a temperature-sensitive polymer, a drug, and light-absorbing particles, and to methods of photothermally modulating drug release.

#2. Description of Related Art

#For a detailed description of the preferred embodiment of the invention, reference will now be made to the accompanying drawings wherein:

#FIG. 1 is a schematic diagram of an optically heatable composition constructed in accordance with a first embodiment of the present invention, showing the composition in its pre-release state;

#FIG. 2 is a schematic diagram of the composition of FIG. 1 showing it in its releasing state;

#Composites of thermally sensitive hydrogels and optically active nanoparticles have been developed for use in photothernally modulated drug delivery. Copolymers of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) exhibit a lower critical solution temperature (LCST) that is slightly above body temperature. When the temperature of the copolymer exceeds the LCST, the hydrogel collapses, causing a rapid release or burst of any soluble material held within the hydrogel matrix.

#In a preferred embodiment, gold-gold sulfide nanoshells, a new class of nanoparticles designed to strongly absorb certain wavelengths of light, have been incorporated into poly(NIPAAm-co-AAm) hydrogels for the purpose of initiating a temperature using the application of light to the composite. Light at wavelengths between 800 and 1200 nm is transmitted through tissue with relatively little attenuation, is absorbed by the nanoparticles, and is converted into heat. Heat generated in this manner causes collapse of the hydrogel in the vicinity causes significantly enhanced release of chemicals and proteins of varying molecular weight from the new composite hydrogels. Additionally, the ability of the present composite hydrogels to release multiple bursts of protein in response to repeated irradiation has been demonstrated.

#In one embodiment of the present photothermally modulated chemical delivery system, near-infrared (near-IR) light is effectively converted to heat within a drug-containing thermally-reversible polymer matrix so as to alter the rate of drug delivery. Special metal coated particles (“nanoshells”) are employed as heat transfer agents within the polymer matrix. Nanoshells have diameters ranging from a few nanometers up to about 5 microns and having defined wavelength absorbance maxima across the visible and infrared range of the electromagnetic spectrum. Gold nanoshells are a preferred class of optically active nanoparticles that consist of a thin layer of gold surrounding a dielectric core, such as gold sulfide (R. D. Averitt et al. J. Opt. Soc. Am. B 16:1824-1832 (1999); and R. D. Averitt et al. Phys. Rev. Lett. 78:4217-4220 (1997) or silicon dioxide (U.S. patent application Ser. No. 09/038,477).