AN INTELLIGENT CHARGE SWITCHABLE POLYMER-LIPID HYBRID SYSTEM FOR IN VIVO DELIVERY OF MOLECULES INCLUDING RNAs
AssigneeQurcan Therapeutics Inc.
InventorsAzhar Zahoor ABBASI, Chunsheng HE, Mohammad Ali AMINI, Xiaoyu WU
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Abstract
Among other things, in general, polymer-lipid nanoparticles (PLNPs) are disclosed that have charge switching properties which allow for efficient release of payloads in the pH environment of the endosome. PLNPs and methods of manufacture thereof are disclosed for charge switchable PLNPs having an anionic polymeric shell surrounding ionizable cationic lipids (also potentially including helper lipids and cholesterol) that are in complex with a cargo (such as, in a non-limiting example, therapeutically useful nucleic acids).
Claims40
A method of synthesizing charge switchable polymer-lipid nanoparticles (PLNPs) encapsulating a cargo, comprising the steps of:
- solubilizing lipids in an alcohol or organic solvent;
- solubilizing the cargo in an acidic aqueous solvent;
- solubilizing an anionic polymer in an aqueous solvent;
- rapidly mixing the solubilized lipids and cargo under stirring to obtain a lipid/cargo complex;
- adding the solubilized anionic polymer aqueous solution to the lipid/cargo complex to form a polymer/lipid-cargo emulsion;
- and
- homogenizing the polymer/lipid-cargo emulsion to obtain cargo loaded PLNPs, wherein the lipids are a mixture of ionizable cationic lipids, cholesterol, and helper lipids and wherein the anionic polymer is an amphiphilic polymer having a backbone and side chains, each of which includes carboxylic groups along at least a portion of its length.
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A charge switchable polymer-lipid nanoparticle (PLNP) comprising:
- an anionic polymer, the anionic polymer being an amphiphilic polymer having a backbone and side chains, each of which includes carboxylic groups along at least a portion of its length;
- ionizable cationic lipids;
- cholesterol;
- a helper lipids;
- a cargo,
- wherein the ionizable cationic lipids form a complex with the cargo,
- wherein the anionic polymer forms a shell surrounding the complex, and
- wherein the shell presents a negative charge under physiological conditions and protonates when the pH is below 6.
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Dependencies are inferred from the claim text.