Micelles and vesicles for the delivery of glycopeptides
Methods for quality control and optimizing the formation and characterization of micelles, vesicles or other aggregates are described herein. Pharmaceutically relevant peptides may be modified to form glycopeptide surfactants which form micelles or other aggregates with another surfactant. Glycopeptide and glycolipid surfactants can aggregate to form particles that enhance drug delivery. The glycopeptide surfactants may be drugs or pro-drugs which are delivered via the micelles or other aggregated structures.
1. A method of optimizing formation of a glycoaggregate, the method comprising:
a. forming a first glycoaggregate from at least two co-surfactants according to two or more reaction parameters, wherein the at least two co-surfactants comprises a glycopeptide and a lipid;
b. characterizing the first glycoaggregate using Diffusion Ordered Spectroscopy (DOSY) to determine a first diffusion coefficient;
c. modifying at least one of the reaction parameters;
d. forming a second glycoaggregate from at least two co-surfactants according to the modified reaction parameters, wherein the at least two co-surfactants comprises a glycopeptide and a lipid;
e. characterizing the second glycoaggregate using DOSY to determine a second diffusion coefficient; and
f. comparing the first and second diffusion coefficients to determine if the first glycoaggregate or the second glycoaggregate is more suitable for a specific application, wherein the specific application is drug delivery.
2. The method of claim 1 , wherein the first glycoaggregate is a micelle or vesicle.
3. The method of claim 1 , wherein the second glycoaggregate is a micelle or vesicle.
4. The method of claim 1 , wherein the reaction parameters are selected from the group comprising a number of the co-surfactants, a selection of the co-surfactants, a ratio of the co-surfactants, a concentration of the co-surfactants, an order of addition of the co-surfactants, a reaction temperature, a mixing time, a presence of a catalyst, and a type of solvent system.
5. The method of claim 1 , wherein the glycopeptide is a drug or a pro-drug.
6. The method of claim 1 , wherein the glycopeptide is synthesized by providing a peptide, providing a saccharide, and covalently linking the peptide with the saccharide, thereby forming said glycopeptide.
7. The method of claim 6 , wherein the peptide includes a serine residue, wherein the saccharide is linked to the serine residue.
8. The method of claim 6 , wherein the saccharide is a glucose.
9. The method of claim 6 , wherein the peptide is a drug or a pro-drug.
10. The method of claim 1 , wherein the glycopeptide is a glycosylated opioid peptide.
11. The method of claim 1 , wherein the glycopeptide is lactomorphin.
12. The method of claim 1 , wherein the lipid is a glycolipid according to any one of the following structures:
wherein R 1 is H, OH, O-β-D-Glucose, O-β-D-Galactose, or O-α-D-Glucose;
wherein R 2 is H or OH;
wherein the chain is according to any one of the following formulas:
wherein n is 6, 8, or 10.
13. The method of claim 1 , wherein the lipid is according to any one of the following structures: