1. An active transdermal system for the release of drugs, the system comprising a control device powered by a battery and a getter device, the getter device comprising particles of activated charcoal and at least a first wall, the first wall being permeable to organic molecules but capable of retaining solid particles, the first wall being coupled to a second wall also capable of retaining solid particles, such that an assembly resulting by the coupling of the first wall and the second wall contains the particles of activated charcoal, wherein the control device is capable of controlling transdermal drug flow from the system through ionic flow from and towards the system, wherein the getter device is located in a region of the system remote from where the ionic flow occurs, and wherein the drugs to be released are in direct contact with the getter device.
2. The active transdermal system according to claim 1, wherein the first wall comprises a continuous polymeric sheet.
3. The active transdermal system according to claim 1, wherein the first wall comprises a fabric of polymeric fibers, the fabric being woven or non-woven.
4. The active transdermal system according to claim 1, wherein the first wall comprises a material selected from sheets or fibers, the sheets or fibers being selected from polyolefin, polyester and Teflon.
5. The active transdermal system according to claim 1, wherein the first and second wall are mutually coupled by heat sealing.
6. The active transdermal system according to claim 1, wherein the second wall of the getter device is selected from a continuous polymeric sheet, woven fabrics, and non-woven fabrics.
7. The active transdermal system according to claim 1, wherein the second wall of the getter device is a portion of an internal surface of an envelope of the system itself.
8. The active transdermal system of claim 1, wherein the getter device is remote from the control device, the battery, and any interconnection between the control device and the battery.
9. An active transdermal system for release of drugs comprising:
an electrode adapted to release drugs from the system;
a control device to control the polarity of the electrode;
a battery to power the control device;
a drug dispersed within the system, the drug adapted to be transdermally released from the system through control exerted by the control device on the electrode; and
a getter device in contact with the drug, permeable to the drug and capable of retaining particles released by the battery, the getter device being located inside the system remote from the electrode and outside a path from the control device to the electrode.
10. The active transdermal system of claim 9, wherein the control device is a microcomputer.
11. The active transdermal system of claim 9, wherein the system forms an envelope and wherein the getter device is in touch with an internal surface of the envelope and not in touch with the control device, the battery or the electrode.
12. The active transdermal system of claim 11, wherein the getter device is remote from an interconnection between the control device and the electrode.
13. The active transdermal system of claim 9, wherein the getter device contains particles of activated charcoal.
14. The active transdermal system of claim 13, wherein the getter device comprises a first wall and a second wall coupled with the first wall, and wherein the particles of activated charcoal are located between the first wall and the second wall.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. An ocular implant comprising a small interfering RNA (siRNA) complexed with a transfection agent, the transfection agent selected from the group consisting of cationic lipids and cell penetration peptides, wherein said complex is associated with a biocompatible polymer, wherein said biocompatible polymer comprises a polymeric matrix configured to release said complex into the eye of a patient at therapeutic levels for a time sufficient to treat an ocular condition or disease.
2. The implant of claim 1, wherein said cell penetration peptide is selected from the group consisting of polylysine peptides, polyarginine peptides, Pep-1 (SEQ ID NO:1), and MPG (SEQ ID NO:2).
3. The implant of claim 1, wherein said transfection agent is a cationic lipid.
4. The implant of claim 3, wherein said cationic lipid is selected from the group consisting of Cetyl trimethylammonium bromide, Cetylpyridinium chloride, Polyethoxylated tallow amine, Benzalkonium chloride, Benzethonium chloride, 1,2-distearoyl-sn-glycero-3-ethyl phosphocholine chloride, Dimethyldioctadecylammonium bromide, and 1,2-dioleoyl-3-trimethylammonium-propane chloride.
5. In a method for increasing the duration of the release of siRNA from an ocular implant, the improvement comprising increasing the loading of siRNA by complexing said siRNA with a transfection agent selected from the group consisting of cationic lipids and cell penetration peptides, and associating said complex with a biocompatible polymer.
6. The method of claim 5, wherein said cell penetration peptide is selected from the group consisting of polylysines, polyarginines, Pep-1 (SEQ ID NO:1), and MPG (SEQ ID NO:2).
7. The method of claim 5 wherein said cationic lipid is selected from the group consisting of Cetyl trimethylammonium bromide, Cetylpyridinium chloride, Polyethoxylated tallow amine, Benzalkonium chloride and Benzethonium chloride.
8. A biodegradable ocular implant, comprising a small interfering RNA (siRNA), a transfection agent, and a biodegradable polymer, wherein the siRNA is complexed with the transfection agent, and wherein said complex is associated with the biodegradable polymer, the transfection agent selected from the group consisting of cell penetration peptides and cationic lipids.
9. The implant of claim 8, wherein the transfection agent is a cell penetration peptide selected from the group consisting of polylysine peptides, polyarginine peptides, R9, Pep-1 (SEQ ID NO:1), and MPG (SEQ ID NO:2).
10. The implant of claim 8, wherein the transfection agent is a cationic lipid selected from the group consisting of Cetyltrimethylammonium bromide, Cetylpyridinium chloride, Polyethoxylated tallow amine, Benzalkonium chloride, Benzethonium chloride, 1,2-distearoyl-sn-glycero-3-ethyl phosphocholine chloride, Dimethyldioctadecylammonium bromide, and 1,2-dioleoyl-3-trimethylammonium-propane chloride.
11. The implant of claim 8, wherein the biodegradable polymer comprises a poly (D,L-lactide-co-glycolide) (PLGA) copolymer or a poly (D,L-lactide) (PLA) polymer or both a PLGA copolymer and PLA polymer.
12. The implant of claim 8, wherein the implant consists essentially of about 14% by weight siRNA, about 81% by weight biodegradable polymer, and about 5% by weight transfection agent, wherein the transfection agent is a cationic lipid or peptide, wherein the implant provides sustained release of an siRNA for at least 24 hours after placement in an eye.
13. The implant of claim 8, wherein the implant consists of about 14% by weight siRNA, about 81% by weight biodegradable polymer, and about 5% by weight transfection agent, wherein the transfection agent is a cationic lipid or peptide, wherein the implant provides sustained release of an siRNA for at least 24 hours after placement in an eye.
14. An ocular implant according to claim 1 or 8, wherein the transfection agent is a cell penetration peptide and the implant is made by the process comprising the steps of:
(a) mixing a cell penetration peptide with an siRNA in aqueous solution, followed by
(b) lyophilizing the solution into a dry powder, followed by
(c) blending the dry powder of (b) with a dry biodegradable polymer powder, the polymer selected from the group consisting of a polylactide (PLA) and a poly(lactide-co-glycolide) (PLGA), followed by
(d) heating the blend of (c) for a time and at a temperature sufficient to form a semi-molten material, followed by
(e) extruding the material of (d) at the temperature sufficient to form the semi-molten material, thereby forming the ocular implant.
15. An ocular implant according to claim 1 or 8, wherein the transfection agent is a cationic lipid and the implant is made by the process comprising the steps of:
(a) dissolving the cationic lipid in ethanol, followed by
(b) mixing the ethanol solution of (a) with an aqueous solution of siRNA, followed by
(c) lyophilizing the mixture of (b) into a dry powder, followed by
(d) blending the dry powder of (c) with a dry biodegradable polymer powder, the polymer selected from the group consisting of a polylactide (PLA) and a poly(lactide-co-glycolide) (PLGA), followed by
(e) heating the blend of (d) for a time and at a temperature sufficient to form a semi-molten material, followed by
(f) extruding the material of (e) at the temperature sufficient to form the semi-molten material, thereby forming the ocular implant.