Use of tetrapeptides and functionalised microcapsules as skin penetration carriers
Microcapsules contain a peptide (I), and peptides (II) or (III) coupled to a PLGA-containing polymeric shell. The microcapsules can be used to enhance skin penetration of active ingredients encapsulated therein, particularly in the field of cosmetics. A process can be used for preparing the microcapsules, and compositions can contain said microcapsules. The microcapsules can be used as a transdermal delivery system for the active ingredients encapsulated therein.
1. A microcapsule, comprising:
a polymeric shell comprising poly(D,L-lactide-co-glycolide) acid (PLGA),
a first peptide of formula (I)
(I)
(SEQ ID NO: 3-NH 2 )
D-Arg-Tyr-Orn-Phe-NH 2
coupled to said polymeric shell, and
a second peptide selected from the group consisting of a peptide of formula (II) and a peptide of formula (III)
(II)
(SEQ ID NO: 1-NH 2 )
Lys-Phe-Asn-Leu-Pro-Ala-Gly-Asn-
Tyr-Lys-Lys-Pro-NH 2 ,
and
(III)
(SEQ ID NO: 2-OH)
Lys-Thr-Thr-Lys-Ser-OH,
coupled to said polymeric shell.
2. The microcapsule according to claim 1 , wherein an average particle size as determined by Dynamic Light Scattering is between 100 to 1000 nm.
3. The microcapsule according to claim 1 , wherein the polymeric shell comprises the PLGA and at least one further polymer.
4. The microcapsule according to claim 1 , wherein the polymeric shell comprises more than one layer.
5. The microcapsule according to claim 4 , wherein the microcapsule is a bilayered microcapsule, comprising an inner layer and an outer layer.
6. The microcapsule according to claim 5 , wherein the outer layer comprises poly (vinyl alcohol) (PVA).
7. The microcapsule according to claim 1 , wherein the polymeric shell encapsulates at least one active ingredient.
8. A process for the preparation of microcapsules as defined in claim 1 , comprising:
a) coupling the first peptide of formula (I) to a first portion of a first microcapsule shell-forming polymeric material, to obtain a first material;
b) preparing an activated form of a second portion of the first microcapsule shell-forming polymeric material by reaction with a suitable coupling agent, to obtain a second material;
c) adding a solution of the first material obtained in a) in a first solvent and a solution of the second material obtained in b) in a second solvent, to an aqueous solution,
wherein the aqueous solution optionally comprises a second shell-forming polymeric material and optionally comprises a material to be encapsulated,
thereby obtaining a colloidal suspension;
d) evaporating said first solvent and second solvent, to obtain a third material;
e) adding the second peptide selected from the group consisting of the peptide of formula (II) and the peptide of formula (III), to the third material obtained in d), to obtain a mixture;
f) incubating the mixture resulting from e), wherein the microcapsules functionalized with said first peptide and second peptide are obtained; and
g) isolating the microcapsules functionalized with said first peptide and second peptide.
9. A composition, comprising:
the microcapsule as defined in claim 1 , and
at least one cosmetically acceptable excipient and/or adjuvant.
10. A method for the preparation of microcapsules, the method comprising:
forming at least one microcapsule having an outer layer comprising a peptide of formula (I)
(I)
(SEQ ID NO: 3-NH 2 )
D-Arg-Tyr-Orn-Phe-NH 2 .
11. The method according to claim 10 , wherein the outer layer further comprises a second peptide selected from the group consisting of a peptide of formula (II) and a peptide of formula (III)
(II)
(SEQ ID NO: 1-NH 2 )
Lys-Phe-Asn-Leu-Pro-Ala-Gly-Asn-
Tyr-Lys-Lys-Pro-NH 2 ,
and
(III)
(SEQ ID NO: 2-OH)
Lys-Thr-Thr-Lys-Ser-OH.
12. A transdermal delivery system, comprising the microcapsule according to claim 7 ,
wherein the at least one active ingredient is encapsulated therein.
13. The transdermal delivery system according to claim 12 , wherein the transdermal delivery system directs the at least one active ingredient towards mitochondria.
14. A method for the transdermal delivery of active ingredients, the method comprising:
administering the microcapsule according to claim 1 to skin, wherein the microcapsule comprises at least one active ingredient encapsulated therein.
15. The method according to claim 14 , wherein the at least one active ingredient is targeted to achieve its effect in mitochondria.
16. The microcapsule according to claim 2 , wherein the average particle size is from 150 to 450 nm.
17. The microcapsule according to claim 2 , wherein the average particle size is from 180 to 400 nm.
18. The microcapsule according to claim 7 , wherein the at least one active ingredient is at least one cosmetic agent.