COMPOSITIONS FOR DRUG ADMINISTRATION
The present invention provides compositions and methods and for increasing the bioavailability of therapeutic agents in a subject. The compositions include at least one alkyl glycoside and at least one therapeutic agent, wherein the alkylglycoside has an alkyl chain length from about 10 to about 16 carbon atoms. In various aspects, the invention provides compositions and methods for oral delivery of peptides containing non-naturally occurring structures including D-amino acids and/or chain cyclization.
1 . A composition comprising:
a) a peptide, wherein the peptide comprises a D-amino acid or a site for cyclization, or combination thereof; and
b) at least one alkylsaccharide, wherein the alkylsaccharide provides increased enteral absorption of the peptide.
2 . The composition of claim 1 , wherein the peptide is octreotide or an analog thereof.
3 . The composition of claim 1 , wherein the alkylsaccharide comprises an alkyl chain having between about 10 to 16 carbons.
4 . The composition of claim 3 , wherein the alkylsaccharide is selected from the group consisting of n-dodecyl maltoside, n-tetradecyl maltoside, n-tridecyl maltoside or sucrose mono-dodecanoate, sucrose mono-tridecanoate, and sucrose mono-tetradecanoate
5 . The composition of claim 1 , wherein the composition is formulated for oral or nasal delivery.
6 . The composition of claim 1 , wherein the composition is formulated as a tablet, liquid or capsule.
7 . The composition of claim 1 , wherein the alkylsaccharide concentration is between about 0.05% and 10% (w/v).
8 . The composition of claim 7 , wherein the alkylsaccharide concentration is between about 0.05% and 1% (w/v).
9 . The composition of claim 1 , wherein the composition exhibits a biphasic increase in serum levels of the peptide upon nasal or oral administration.
10 . The composition of claim 1 , wherein the bioavailability of the peptide is increased 2, 3, or 4 times upon nasal or oral administration as compared to bioavailability upon subcutaneous administration.
11 . A method of increasing enteral adsorption of a peptide in a biphasic manner comprising orally or nasally administering to a subject a composition comprising:
a) at least one peptide, wherein the peptide comprises a D-amino acid or a site for cyclization, or combination thereof; and
b) at least one alkylsaccharide, wherein the enteral absorption of the peptide is increased and systemic serum levels of the peptide are increased in a biphasic manner.
12 . The method of claim 11 , wherein the peptide is octreotide or an analog thereof.
13 . The method of claim 11 , wherein the alkylsaccharide comprises an alkyl chain having between about 10 to 16 carbons.
14 . The method of claim 13 , wherein the alkylsaccharide is selected from the group consisting of n-dodecyl maltoside, n-tetradecyl maltoside, n-tridecyl maltoside or sucrose mono-dodecanoate, sucrose mono-tridecanoate, and sucrose mono-tetradecanoate
15 . The method of claim 11 , wherein the composition is formulated as a tablet, liquid or capsule.
16 . The method of claim 11 , wherein the alkylsaccharide concentration is between about 0.05% and 10% (w/v).
17 . The method of claim 16 , wherein the alkylsaccharide concentration is between about 0.05% and 1% (w/v).
18 . The method of claim 12 , wherein the C max is 2, 3, 4, 5, 6, 7, 8 or 9-fold greater as compared to delivery without alkylsaccharide.