Compositions and methods for drug delivery using pH sensitive molecules
View Patent ↗A system relating to the delivery of desired compounds (e.g., drugs and nucleic acids) into cells using pH-sensitive delivery systems. The system provides compositions and methods for the delivery and release of a compound to a cell.
1. A process for transfecting a nucleic acid into a cell in vivo, comprising:
a) attaching a membrane activity inhibitor to a membrane active peptide via a labile linkage, wherein the inhibitor is detached within the cell;
b) adding the peptide to a solution containing the nucleic acid;
c) delivering the peptide and nucleic acid to the cell, wherein the peptide and the nucleic acid are endocytosed; and,
d) transfecting the cell.
2. The process of claim 1 wherein the peptide consists of pardaxin.
3. The process of claim 1 wherein the peptide consists of KL3.
4. The process of claim 1 wherein the peptide consists of magainin.
5. The process of claim 1 wherein the labile linkage is selected from the group consisting of pH-labile, very pH labile, and extremely pH-labile.
6. The process of claim 1 wherein the labile linkage is selected from the group consisting of disulfide, acetal, ketal, enol ether, enol esters amide, imine, imminium, enamine, allyl ether, silazane, and silyl enol ether bonds.
7. The process of claim 1 wherein the labile linkage is selected from the group consisting of dials, diazo, ester, sulfone, and silicon-carbon bonds.
8. A process for transfecting a nucleic acid into a cell in vivo, comprising:
a) attaching a reversible labile membrane activity inhibitor to a melittin peptide wherein the inhibitor is detached upon association with the cell;
b) adding the peptide to a solution containing the nucleic acid;
c) contacting the peptide and nucleic acid with the cell, wherein the peptide and nucleic acid are endocytosed; and,
d) transfecting to cell.
9. A process for transfecting a nucleic acid into a cell in vivo, comprising:
a) attaching a membrane activity inhibitor to a membrane active polymer via a labile linkage wherein the inhibitor is detached upon association with the cell;
b) adding the membrane active polymer to a solution containing the nucleic acid;
c) contacting the membrane active polymer and nucleic acid with the cell wherein the membrane active polymer and the nucleic acid are endocytosed; and,
d) transfecting the cell.
10. The process of claim 9 wherein the labile linkage is selected from the group consisting of pH-labile, very pH labile, and extremely pH-labile.
11. The process of claim 9 wherein the labile linkage is selected from the group consisting of disulfide, acetal, ketal, enol ether, enol ester, amide, imine, imminium, enamine, silyl ether, silazane, and silyl enol ether bonds.
12. The process of claim 9 wherein to labile linkage is selected from the group consisting of diols, diazo, ester, sulfone, and silicon-carbon bonds.