Layered silicate nanoparticles for controlled delivery of therapeutic agents from medical articles
Medical articles (for instance, a drug delivery patch or an implantable or insertable medical device) are provided that comprise a release region, which in turn comprises (a) polymeric carrier comprising a polymer (for instance, a hydrophobic polymer) and (b) drug loaded nanoparticles, which are dispersed within the polymeric carrier. The drug loaded nanoparticles comprise a layered silicate material (for instance synthetic or naturally occurring smectite clay nanoparticles) and a therapeutic agent (for instance, a hydrophilic or hydrophobic therapeutic agent). Also described are methods of releasing a therapeutic agent to a patient using such medical articles, and methods of making such medical articles.
1 . A medical article comprising a release region, said release region comprising (a) polymeric carrier comprising a first polymer and (b) drug loaded nanoparticles dispersed within said polymeric carrier, said drug loaded nanoparticles comprising a layered silicate material and a first therapeutic agent.
2 . The medical article of claim 1 , wherein said first therapeutic agent is a hydrophilic therapeutic agent and said first polymer is a hydrophobic polymer.
3 . The medical article of claim 2 , wherein said medical article is a vascular medical device, wherein said first therapeutic agent is halofuginone.HBr, and wherein said first polymer is a polyolefin-polyvinylaromatic block copolymer.
4 . The medical article of claim 1 , wherein said first therapeutic agent is a hydrophobic therapeutic agent and said first polymer is a hydrophilic polymer.
5 . The medical article of claim 1 , further comprising a second polymer.
6 . The medical article of claim 5 , wherein said polymeric carrier further comprises said second polymer.
7 . The medical article of claim 5 , wherein said nanoparticles further comprise said second polymer.
8 . The medical article of claim 7 , wherein said second polymer is hydrophobic and said first polymer is hydrophilic.
9 . The medical article of claim 7 , wherein said second polymer is hydrophilic and said first polymer is hydrophobic.
10 . The medical article of claim 9 , wherein said medical article is a vascular medical device, wherein said first therapeutic agent is halofuginone.HBr, wherein said first polymer is a polyolefin-polyvinylaromatic block copolymer, and wherein said second polymer is a hydrophilic polymer selected from hyaluronic acid, collagen, heparin, chrondroitin sulfate, phosphoro choline, dextran, and polyethylene oxide.
11 . The medical article of claim 1 , wherein said polymeric carrier further comprises said first therapeutic agent.
12 . The medical article of claim 1 , further comprising a second therapeutic agent.
13 . The medical article of claim 12 , wherein said polymeric carrier further comprises said second therapeutic agent.
14 . The medical article of claim 13 , wherein said first therapeutic agent is hydrophilic and said second therapeutic agents is hydrophobic.
15 . The medical article of claim 12 , wherein said nanoparticles further comprise said second therapeutic agent.
16 . The medical article of claim 15 , wherein said first and second therapeutic agents are hydrophilic.
17 . The medical article of claim 1 , wherein said release region is disposed over at least a portion of a medical article substrate.
18 . The medical article of claim 1 , wherein said medical article is an implantable or insertable medical device.
19 . The medical article of claim 18 , wherein said implantable or insertable medical device is adapted for implantation or insertion into the coronary or peripheral vasculature.
20 . The medical article of claim 19 , wherein said implantable or insertable medical device is adapted for implantation or insertion into the esophagus, trachea, colon, biliary tract, urinary tract, prostate or brain.
21 . The medical article of claim 19 , wherein said implantable or insertable medical device is selected from a catheter, a guide wire, a balloon, a filter, a stent, a stent graft, a vascular graft, a vascular patch, a shunt, an electrode, a heart valve, a circulation pump, and an intraluminal paving system.
22 . The medical article of claim 19 , wherein said therapeutic agent is selected from an anti-thrombotic agent, an anti-proliferative agent, an anti-inflammatory agent, an anti-migratory agent, an agent affecting extracellular matrix production and organization, an antineoplastic agent, an anti-mitotic agent, an anesthetic agent, an anti-coagulant, a vascular cell growth promoter, a vascular cell growth inhibitor, a cholesterol-lowering agent, a vasodilating agent, and an agent that interferes with endogenous vasoactive mechanisms.
23 . The medical article of claim 1 , wherein said wherein said layered silicate material comprises synthetic or naturally occurring smectite.
24 . The medical article of claim 1 , wherein said wherein said layered silicate material comprises a natural or synthetic silicate material selected from bentonite, aliettite, vermiculite, swinefordite, montmorillonite, yakhontovite, nontronite, beidellite, volkonskoite, stevensite, hectorite, saponite, laponite, sauconite, magadiite, kenyaite and ledikite.
25 . A method of releasing a therapeutic agent to a patient comprising: (a) providing the medical article of claim 1; and (b) contacting said medical article with a patient.
26 . A method of providing the medical article of claim 1 comprising:
providing a release-region-forming fluid comprising (a) said first polymer species and (b) said drug loaded nanoparticles; and
applying said release-region-forming fluid to a medical article substrate or to a releasable template.