Micellar nanoparticles and uses thereof
Inventors
Ryu, Jin-Hyeob • LIM, Yu Na • Min, Hyun Su • KOH, Han Seok • Kim, Dae Hoon • Cho, Hyun-Jeong
Assignees
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Publication Number
US-11839624-B2
Publication Date
2023-12-12
Expiration Date
Abstract
The present disclosure includes cationic carrier units comprising (i) a water soluble polymer, (ii) a positively charged carrier, and (iii) an adjuvant moiety, wherein when the cationic carrier unit is mixed with an anionic payload (e.g., an antisense oligonucleotide) that electrostatically interacts with the cationic carrier unit, the resulting composition self-organizes into a micelle encapsulating the anionic payload in its core. The cationic carrier units can also comprise a tissue specific targeting moiety, which would be displayed on the surface of the micelle. The disclosure also includes micelles comprising the cationic carrier units of the disclosure, methods of manufacture of cationic carrier units and micelles, pharmaceutical compositions comprising the micelles, and also methods of treating diseases or conditions comprising administering the micelles to a subject in need thereof.
Core Innovation
The invention relates to a micelle comprising a plurality of cationic carrier units and an anionic payload. Each cationic carrier unit includes a water-soluble biopolymer moiety comprising polyethylene glycol (PEG), a positively charged carrier moiety comprising polylysine, an adjuvant moiety comprising 20 to 50 vitamin B3 units, and a targeting moiety comprising a ligand that can be transported by large neutral amino acid transporter 1 (LAT1).
Within the polylysine, some lysine units are covalently linked to the adjuvant moiety as AM-linked lysine units, and each AM-linked lysine unit is covalently linked to a vitamin B3 unit. The PEG and the positively charged polylysine are attached directly or through a bifunctional linker, and the charged carrier moieties of the cationic carrier units and the anionic payload are associated with each other via a covalent bond, a non-covalent bond, or an ionic bond.
The disclosed targeting concept covers LAT1-transportable ligands, including phenylalanine, tryptophan, and tyrosine. The anionic payload includes nucleic acids such as siRNA, shRNA, antisense oligonucleotides, antimir, miRNA, mRNA, and other nucleic-acid types, with nucleic-acid analog content including LNA and other specified analogs.
Claims Coverage
The provided claim content includes one independent claim directed to a LAT1-targeting cationic micelle with defined PEG, polylysine, vitamin B3, and anionic payload features.
Lat1-targeted vitamin B3-adjuvanted peg-polylysine micelle
A micelle comprising a plurality of cationic carrier units and an anionic payload, wherein each cationic carrier unit includes a water-soluble biopolymer moiety comprising polyethylene glycol (PEG), a positively charged carrier moiety comprising polylysine, an adjuvant moiety comprising 20 to 50 vitamin B3 units, and a targeting moiety comprising a ligand that can be transported by large neutral amino acid transporter 1 (LAT1).
Am-linked lysine units covalently linked to vitamin B3
The polylysine comprises some lysine units covalently linked to the adjuvant moiety as AM-linked lysine units, and each AM-linked lysine unit is covalently linked to a vitamin B3 unit.
Charge-associated anionic payload
The charged carrier moieties of the plurality of cationic carrier units and the anionic payload are associated with each other via a covalent bond, a non-covalent bond, or an ionic bond.
Direct or bifunctional-linker attachment between PEG and polylysine
The water-soluble biopolymer moiety comprising PEG and the positively charged carrier moiety comprising polylysine are attached directly or through a bifunctional linker.
The claims center on a LAT1-transportable targeting micelle built from PEG and positively charged polylysine, with vitamin B3 introduced through AM-linked lysine units and with anionic payload association through covalent, non-covalent, or ionic interactions.
Stated Advantages
Electrostatic protection of the anionic payload from DNase and RNase.
Tunable micelle size and charge characteristics.
BBB delivery using LAT1-transportable targeting ligands.
Documented Applications
Anti-miRNA delivery system and delivery of nucleic-acid payloads such as antisense oligonucleotides and other nucleic-acid types.
BBB delivery using LAT1-transportable targeting ligands.
Drug treatment of neurodegenerative disease, including Alzheimer’s disease.
Cancer targeting.
Delivery contexts involving targeting miRNA-485-3p.
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