Fat-soluble vitamin compounds for targeting drug delivery and enhancing siRNA activity

• Main Authors: HOU, ZHENG, KARMALI, PRIYA, PAYNE, JOSEPH E, AKOPIAN, VIOLETTA, NAGARAJAN, SRIDHAR C, KNOPOV, VICTOR, AHMADIAN, MOHAMMAD, PERELMAN, LOREN A, WITTE, RICHARD P, GAUDETTE, JOHN A, TANAKA, YASUNOBU, NIITSU, YOSHIRO
• Format: Patent
• Language: Chinese; English
• Published: 01.04.2013
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

Here described are compounds of formula I: wherein R1 and R2 is independently selected from a group consisting of C10 to C18 alkyl, C12 to C18 alkenyl, and oleoyl group; wherein R3 and R4 are independently selected from a group consisting of H, C1 to C6 alkyl, and C1 to C6 alkanol; wherein X is selected from a group consisting of -CH2-, -S-, and -O-; wherein Y is selected from -(CH2)n, -S(CH2)n, -O(CH2)n-, thiophene, -SO2(CH2)n-, and ester, wherein n = 1-4; and wherein Z is a counterion; and compounds consisting of the structure (targeting molecule)n-linker-(targeting molecule)n, wherein the targeting molecule is a retinoid or a fat soluble vitamin having a specific receptor on the target cell; wherein n=0, 1, 2 or 3; and wherein the linker comprises a polyethylene glycol (PEG) or PEG-like molecule, as well as compositions and pharmaceutical formulations including one or both of these compounds which are useful for the delivery of therapeutic agents; and methods of using these compositions and pharmaceutical