Iontophoretic delivery of active agents conjugated to nanoparticles
An iontophoresis device is provided to delivery active agents to a biological interface, the iontophoresis device comprising: an active electrode element operable to provide an electrical potential; and an inner active agent reservoir comprising a plurality of nanoparticles, each nanoparticles being conjugated to a plurality of active agents via respective linkers.
1 . An iontophoresis device for delivering active agents to a biological interface, the iontophoresis device comprising:
an active electrode assembly and a counter electrode assembly, the active electrode assembly including: an active electrode element operable to provide an electrical potential; and a first active agent reservoir comprising a plurality of nanoparticles, each nanoparticle being conjugated to one or more active agents via respective linkers.
2 . The iontophoresis device of claim 1 wherein at least some of the nanoparticles are metallic.
3 . The iontophoresis device of claim 2 wherein at least some of the nanoparticles are gold.
4 . The iontophoresis device of claim 2 wherein at least some of the nanoparticles are silver or titanium oxide.
5 . The iontophoresis device of claim 1 wherein at least some of the nanoparticles are solid, hollow shells or have core/shell structures.
6 . The iontophoresis device of claim 1 wherein the nanoparticles have diameters of about 10-500 nm.
7 . The iontophoresis device of claim 1 wherein at least some of the nanoparticles are coupled to the respective linkers by metal-sulfur bonds.
8 . The iontophoresis device of claim 1 wherein at least some of the linkers are coupled to the respective active agents by carboxylate ester linkages.
9 . The iontophoresis device of claim 1 wherein the linker is a poly(ethylene glycol) derivative.
10 . The iontophoresis device of claim 9 wherein the poly(ethylene glycol) derivative has a molecular weight of about 500-2000 Daltons.
11 . The iontophoresis device of claim 1 wherein at least some of the nanoparticles are charged.
12 . The iontophoresis device of claim 1 wherein at least some of the nanoparticles are electrically neutral.
13 . The iontophoresis device of claim 1 , further comprising:
an electrolyte reservoir comprising an electrolyte composition; and
an inner ion selective membrane positioned between said electrolyte reservoir and said the first active agent reservoir.
14 . The iontophoresis device of claim 13 , further comprising:
an outermost ion selective membrane having an outer surface, the outer surface being proximate the biological interface when in use.
15 . The iontophoresis device of claim 14 , further comprising:
additional active agents cached in the outermost ion selective membrane.
16 . The iontophoresis device of claim 15 wherein the additional active agents are conjugated to respective additional nanoparticles.
17 . The iontophoresis device of claim 13 , further comprising:
further active agents deposited on the outer surface of the outermost ion selective membrane.
18 . The iontophoresis device of claim 17 wherein the further active agents are conjugated to respective further nanoparticles.
19 . The iontophoresis device of claim 1 wherein the active agents can be released by enzymatic cleavage following the delivery.
20 . The iontophoresis device of claim 1 , further comprising:
one or more microneedles.
21 . A method for transdermal administration of an active agent by iontophoresis, comprising:
positioning an active electrode assembly and a counter electrode assembly of an iontophoresis device on a biological interface of a subject, the active electrode assembly including: an active electrode element operable to provide an electrical potential; and a first active agent reservoir comprising a plurality of nanoparticles, each nanoparticle being conjugated to one or more active agents via respective linkers; and
applying a sufficient amount of current to administer a therapeutically effective amount of the active agents conjugated to the nanoparticles in the subject for a limited period of time.
22 . The method of claim 21 wherein at least some of the nanoparticles are metallic.
23 . The method of claim 21 wherein at least some of the nanoparticles are gold.
24 . The method of claim 21 wherein the nanoparticles are coupled to the linkers by metal-sulfur bonds.
25 . The method of claim 21 wherein the linkers are coupled to the active agents by carboxylate ester linkages.
26 . The method of claim 21 wherein the linker is a poly(ethylene glycol) derivative.
27 . The method of claim 21 wherein the nanoparticles remain conjugated to the respective active agents during the transdermal administration.