Formulations for targeted release of agents under low ph conditions and methods of use thereof
AssigneeYale University
InventorsW. Mark SALTZMAN, Junwei ZHANG, Jiangbing ZHOU, Zhaozhong JIANG
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Abstract
Poly(amine-co-ester-co-ortho ester) polymers, methods of forming active agent-load nanoparticles therefrom, and methods of using the nanoparticles for drug delivery are disclosed. The nanoparticles can be coated with an agent that reduces surface charge, an agent that increases cell-specific targeting, or a combination thereof. Typically, the loaded nanoparticles are less toxic, more efficient at drug delivery, or a combination thereof compared to a control or other transfection reagents.
Claims33
A polymeric formulation for delivery of a nucleic acid comprising a poly(amine-co-ester-co-ortho ester) or poly(amine-co-amide-co-ortho ester) having the following formula:
- wherein each occurrence of m is an integer from 1-30,
- each occurrence of n, p, and q is independently an integer from 1-20, and
- each occurrence oft, u, v, and w is independently an integer from 1-1000,
- J and Z are independently O or NR′, wherein R′ is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl.
A method for delivering molecules to a compartment of a cell, wherein the molecule is released at the pH of the compartment, comprising
- providing a poly(amine-co-ester-co-ortho ester) or poly(amine-co-amides-co-orthoester) having the following formula:
- wherein each occurrence of m is an integer from 1-30,
- each occurrence of n, p, and q, is independently an integer from 1-20, and each occurrence of t, u, v, and w is independently an integer from 1-1000,
- J and Z are independently O or NR′, wherein R′ is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl.
- Precipitating molecules to be delivered by mixing the orthoester with the nucleic acid in a solution, and
- Forming the precipitate into nanoparticles.
Dependencies are inferred from the claim text.