Transdermal drug delivery using an osmolyte and vasoactive agent
A formulation and method for delivery of bioactive substances when applied to, or within, the skin or other exterior region of a mammal. for example, a patient, includes a vasoactive agent; an osmolyte; and an active ingredient. The formulation is sufficiently hygroscopic so as to create a condition of hypertonicity when absorbed by the skin. When the formulation is applied to the skin, the vasoactive agent can be delivered to the dermis so as to contact the vasculature of a patient.
1. A formulation for topical delivery of an active ingredient to a mammal, said mammal having a body surface and the body surface having a topical application site comprising skin cells, the formulation comprising:
a vasodilator, an osmolyte, and an active ingredient, wherein:
a) the vasodilator is selected from the group consisting of arginine, methyl nicotinate, naftidrofuryl oxalate, papaverine, tolazoline, and combinations of the foregoing;
b) the osmolyte is a sugar;
c) the active ingredient is selected from the group consisting of sirtuin activator and sirtuin inhibitor; and
d) the vasodilator and the osmolyte are present in amounts effective to work together in a synergistic manner to enable penetration of the active ingredient into or through the skin,
wherein the vasodilator, the osmolyte, and the active ingredient are non-identical and wherein the formulation has an osmolarity that is greater than 350 milliOsmol/L.
2. The formulation of claim 1 , further comprising a component selected from the group consisting of a transpiration barrier, a penetration enhancer, and a drug administration patch.
3. The formulation of claim 1 , further comprising a transpiration barrier, wherein the transpiration barrier includes at least one of a chemical barrier or a physical barrier.
4. The formulation of claim 1 , wherein said formulation is packaged in a water-resistant delivery system.
5. The formulation of claim 1 , wherein the osmolarity is greater than 600 milliOsmol/L.
6. A method for enhancing the penetration of an active ingredient into or through a body surface of a mammal, the method comprising introducing a formulation comprising:
a vasodilator, an osmolyte, and an active ingredient wherein:
a) the vasodilator is selected from the group consisting of arginine, methyl nicotinate, naftidrofuryl oxalate, papaverine, tolazoline, and combinations of the foregoing,
b) the osmolyte is a sugar,
c) the active ingredient is selected from the group consisting of sirtuin activator and sirtuin inhibitor; and
d) the vasodilator and the osmolyte are present in amounts effective to work together in a synergistic manner to enable penetration of the active ingredient into or through the skin,
wherein the vasodilator, the osmolyte, and the active ingredient are non-identical and wherein the formulation has an osmolarity that is greater than 350 milliOsmol/L; and
wherein the formulation is introduced into or onto a region of the body surface comprising skin cells so as to cause the active agent ingredient to cross the body surface.
7. The method of claim 6 , wherein the active ingredient penetrates to at least one of an epidermis, a dermis, or a systemic circulatory vessel of the mammal.
8. The method of claim 6 , wherein the region of the body surface is skin.
9. The method of claim 6 , wherein the osmolarity is greater than 600 milliosmol/L.
10. A method for topical delivery of an active ingredient to a mammal, said mammal having a body surface and said body surface comprising a dermis and a topical application site, the method comprising:
administering a vasodilator to the topical application site, said vasodilator being deliverable to a region of said dermis and said vasodilator being selected from the group consisting of arginine, methyl nicotinate, naftidrofuryl oxalate, papaverine, tolazoline, and combinations of the foregoing,
administering an osmolyte to the topical application site, wherein the osmolyte is a sugar; and
administering the active ingredient to the topical application site, the active ingredient selected from the group consisting of sirtuin activator and sirtuin inhibitor,
wherein the vasodilator, the osmolyte, and the active ingredient are non-identical and wherein the vasodilator, the osmolyte, and the active ingredient have an osmolarity that is greater than 350 milliOsmol/L; and
wherein the vasodilator and the osmolyte are present in amounts effective to work together in a synergistic manner to enable penetration of the active ingredient into or through the skin.
11. The method of claim 10 , wherein the vasodilator and osmolyte are applied sequentially.
12. The method of claim 10 , wherein the vasodilator and osmolyte are applied together.
13. The method of claim 10 , further comprising applying an occlusive barrier to the topical application site.
14. The method of claim 10 , wherein the osmolarity is greater than 600 milliosmol/L.
15. The method of claim 10 , wherein the vasodilator induces an increased blood flow in the body surface.
16. The method of claim 10 , wherein administration of the vasodilator, the osmolyte, and the active ingredient results in passage of the vasodilator through a basement membrane of the body surface.
17. The method of claim 10 , wherein the administered vasodilator and the osmolyte exert a physiological change in the body surface of the mammal to thereby allow transport of the administered active agent through the body surface.
18. The method of claim 17 , wherein the administered vasodilator and the osmolyte exert a physiological change in the body surface of the mammal to thereby allow transport of the administered active agent into at least one of an epidermal tissue of the body surface, a dermal tissue of the body surface, or a portion of a systemic circulatory system of the mammal.