Biodegradable and clinically-compatible nanoparticles as drug delivery carriers
Inventors
Li, Chiang Jia • Li, Youzhi • Gada, Keyur • Dai, Xiaoshu
Assignees
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Publication Number
US-11001840-B2
Publication Date
2021-05-11
Expiration Date
Abstract
The present invention relates to the composition of a nanoparticle based on a magnesium salt, and methods of drug delivery using the nanoparticle. A preferred embodiment uses magnesium phosphate, with or without a shell to deliver aiRNA and/or siRNA. The nanoparticles of the present invention are also effective when administered orally.
Core Innovation
The invention provides a pharmaceutical composition comprising nanoparticles for RNA interference (RNAi) therapeutics. The nanoparticles include a core consisting of a magnesium salt of magnesium phosphate and a medically useful agent comprising ribonucleic acid (RNA), and the core is encapsulated by a shell.
In the disclosed embodiments, the RNA comprises an asymmetric interfering RNA (aiRNA) or a small interfering RNA (siRNA). The shell comprises 1,3-dichloropropan-2-yl carbamate (CAS Registry Number: 61791-12-6) together with protamine or histone, and the nanoparticles are defined by an inorganic magnesium salt core encapsulating an RNAi molecule.
The claims further define the nanoparticle composition and size constraints, including nanoparticles having an average diameter of no more than about 50 nm, and include defining properties such as preventing aggregation in aqueous solution and excluding calcium phosphate.
Claims Coverage
The independent claims cover four core inventive arrangements: a pharmaceutical composition of magnesium phosphate-based nanoparticles with an RNAi payload encapsulated in a shell containing a specified nonionic surfactant and a specified protein, with a nanoparticle size limit; a pharmaceutical composition where the shell contains protamine plus a specified nonionic surfactant; a nanoparticle definition with a magnesium salt core and an RNAi payload encapsulated by a shell with protamine plus the specified nonionic surfactant; and a nanoparticle definition with a magnesium salt core and an RNAi payload encapsulated by a shell with histone plus the specified nonionic surfactant.
Magnesium phosphate RNAi nanoparticle with nonionic surfactant and protein shell and size limit
A pharmaceutical composition comprising nanoparticles wherein at least a plurality of the nanoparticles each comprises a core comprising a magnesium salt consisting of magnesium phosphate and a medically useful agent comprising an RNA consisting of aiRNA or siRNA, wherein the core is encapsulated by a shell comprising a nonionic surfactant and a protein, wherein the nonionic surfactant is 1,3-dichloropropan-2-yl carbamate (CAS Registry Number: 61791-12-6), wherein the protein is protamine or histone, and wherein the nanoparticle has an average diameter of no more than about 50 nm.
Magnesium phosphate RNAi nanoparticle pharmaceutical composition with protamine and 1,3-dichloropropan-2-yl carbamate shell
A pharmaceutical composition comprising nanoparticles wherein at least a plurality of the nanoparticles each comprises a core comprising an inorganic magnesium salt consisting of magnesium phosphate and a medically useful agent comprising an RNA interfering (RNAi) molecule, wherein the core is encapsulated by a shell, wherein the RNAi molecule is an asymmetric interfering RNA (aiRNA) or a small interfering RNA (siRNA), wherein the shell comprises protamine and 1,3-dichloropropan-2-yl carbamate (CAS Registry Number: 61791-12-6).
RNAi magnesium-salt nanoparticle with protamine and 1,3-dichloropropan-2-yl carbamate shell
A nanoparticle comprising a core comprising an inorganic magnesium salt and a medically useful agent comprising an RNA interfering (RNAi) molecule, wherein the core is encapsulated by a shell, wherein the RNAi molecule is an asymmetric interfering RNA (aiRNA) or a small interfering RNA (siRNA), wherein the shell comprises protamine and 1,3-dichloropropan-2-yl carbamate (CAS Registry Number: 61791-12-6).
RNAi magnesium-salt nanoparticle with histone and 1,3-dichloropropan-2-yl carbamate shell
A nanoparticle comprising a core comprising an inorganic magnesium salt and a medically useful agent comprising an RNA interfering (RNAi) molecule, wherein the core is encapsulated by a shell, wherein the RNA comprises an asymmetric interfering RNA (aiRNA) or a small interfering RNA (siRNA), wherein the shell comprises histone and 1,3-dichloropropan-2-yl carbamate (CAS Registry Number: 61791-12-6).
Across the independent claims, the central claim coverage is for nanoparticles with magnesium phosphate or an inorganic magnesium salt cores that encapsulate an RNAi molecule (aiRNA or siRNA), where the shell includes 1,3-dichloropropan-2-yl carbamate (CAS Registry Number: 61791-12-6) combined with either protamine or histone, with at least one independent claim additionally requiring an average diameter of no more than about 50 nm.
Stated Advantages
Nanoparticles prevent aggregation when dispersed in aqueous solution.
Nanoparticles can be produced with an average diameter of no more than about 50 nm.
Documented Applications
Intracellular delivery of RNA interference (RNAi) therapeutics comprising aiRNA and/or siRNA, including in vitro and in vivo gene silencing contexts described in the document summary.
Targeted gene silencing related to β-catenin, PLK1, and Survivin, as described in the document summary.
Oral administration feasibility as described in the document summary.
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