Abstract:
The present invention provides an amphiphilic poly(amino acid) for nucleic acid delivery, which is represented by the following formula (1): where: R1 represents a hydroxy group, an oxybenzyl group, an —O—R1a group, or an —NH—R1b group, where R1a and R1b each independently represent an unsubstituted or substituted, linear or branched alkyl group having 1 to 12 carbon atoms; R2 represents a hydrogen atom, an unsubstituted or substituted, linear or branched alkyl group having 1 to 12 carbon atoms, or an unsubstituted or substituted, linear or branched alkylcarbonyl group having 1 to 24 carbon atoms; R3a, R3b, R4a, and R4b each independently represent a methylene group or an ethylene group; R5a and R5b each independently represent —O— or —NH—; R6a and R6b each independently represent an unsubstituted or substituted aliphatic hydrocarbon group having 7 to 12 carbon atoms that may contain an alicycle; R7a and R7b are each independently selected from groups identical to or different from each other in the group consisting of the following groups: —NH—(CH2)p1—[NH—(CH2)q1—]r1NH2 (i); —NH—(CH2)p2—N[—(CH2)q2—NH2]2 (ii); —NH—(CH2)p3—N{[—(CH2)q3—NH2][—(CH2)q4—NH—]r2H} (iii); and —NH—(CH2)p4—N{—(CH2)q5—N[—(CH2)q6—NH2]2}2 (iv), where p1 to p4, q1 to q6, and r1 and r2 each independently represent an integer of from 1 to 5; R8 represents a side chain of an amino acid selected from the group consisting of ornithine, lysine, homolysine, arginine, homoarginine, and histidine; m represents an integer of 9 or more; n represents an integer of from 0 to m; x represents an integer of from 2 to 300; y represents an integer of from 0 to x; and z represents an integer of from 0 to x, provided that a relationship of y+z≤x and a relationship of 11≤m+x≤400 are satisfied, and repeating units in the formula (1) may be randomly present.
Abstract:
A unit structure-type pharmaceutical composition includes a single nucleic acid, such as an antisense nucleic acid, electrostatically bound to a single block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment. The negative charges of the nucleic acid are counterbalanced, at least substantially, by the positive charges of the cationic polyamino acid segment such that the pharmaceutical composition is electrically neutral or nearly electrically neutral. Further, the nucleic acid is covered with the hydrophilic polymer chain segment. The block copolymer thereby improves the blood retention capability of the nucleic acids.
Abstract:
The present invention provides a vesicle, a conjugate, a composition comprising the vesicle or the conjugate, for use in delivering a drug to the brain, and a method for administering the same. The composition of the present invention is a composition for administration to a subject according to a dosing regimen, comprising a carrier for drug delivery, wherein the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject, and the carrier is modified at the outer surface thereof with a GLUT1 ligand.
Abstract:
A unit structure-type pharmaceutical composition includes at least one nucleic acid, such as siRNA, electrostatically bound to at least one block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment. The negative charge(s) of the nucleic acid are counterbalanced, at least substantially, by the positive charge(s) of the cationic polyamino acid segment such that the pharmaceutical composition is electrically neutral or nearly electrically neutral. Further, the nucleic acid is covered with the hydrophilic polymer chain segment(s). The at least one block copolymer thereby improves the blood retention capability of the nucleic acid(s).
Abstract:
The present invention provides a vesicle, a conjugate, a composition comprising the vesicle or the conjugate, for use in delivering a drug to the brain, and a method for administering the same. The composition of the present invention is a composition for administration to a subject according to a dosing regimen, comprising a carrier for drug delivery, wherein the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject, and the carrier is modified at the outer surface thereof with a GLUT1 ligand.
Abstract:
A unit-type polyion complex for use in delivering nucleic acid to a target site in a patient includes one or more molecules of a block copolymer having a poly(ethylene glycol) segment and a cationic poly(amino acid) segment and one or more molecules of a nucleic acid. A total quantity of positive charges derived from side chains of the cationic poly(amino acid) segment of the block copolymer in the unit-type polyion complex is not offset by a total quantity of negative charges derived from the nucleic acid. Furthermore, the nucleic acid has a strand length of 10-50 bases, the molecular weight of the poly(ethylene glycol) segment is 40×103 or more, and the block copolymer has a binding constant (Ka) for the nucleic acid of 3.0×105 or more.
Abstract:
The present invention provides a vesicle, a conjugate, a composition comprising the vesicle or the conjugate, for use in delivering a drug to the brain, and a method for administering the same. The composition of the present invention is a composition for administration to a subject according to a dosing regimen, comprising a carrier for drug delivery, wherein the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject, and the carrier is modified at the outer surface thereof with a GLUT1 ligand.
Abstract:
A unit structure-type pharmaceutical composition includes at least one nucleic acid, such as siRNA, electrostatically bound to at least one block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment. The negative charge(s) of the nucleic acid are counterbalanced, at least substantially, by the positive charge(s) of the cationic polyamino acid segment such that the pharmaceutical composition is electrically neutral or nearly electrically neutral. Further, the nucleic acid is covered with the hydrophilic polymer chain segment(s). The at least one block copolymer thereby improves the blood retention capability of the nucleic acid(s).
Abstract:
This invention provides an antitumor drug delivery formulation for treating a subject having a tumor more highly expressing a TUG1 gene than normal tissues or preventing the subject from tumor metastasis, comprising a polymeric micelle comprising a nucleic acid that suppresses high expression of the TUG1 gene as an active ingredient, wherein the polymeric micelle comprises a block copolymer having a cationic poly(amino acid) segment and a hydrophilic polymer chain segment and the nucleic acid, and wherein the nucleic acid is bound to a cationic group of the cationic poly(amino acid) segment to form a complex and/or the nucleic acid is incorporated in the micelle or attached into the micelle; and the polymeric micelle accumulates in the tumor.
Abstract:
Provided are a micelle composition for nucleic acid delivery using a temperature-sensitive polymer, and a method for producing the micelle. For example, provided is a polyion complex comprising a temperature-sensitive copolymer and a nucleic acid, wherein the temperature-sensitive copolymer comprises a cationic block and a temperature-sensitive block, the cationic block optionally carrying a hydrophilic block linked thereto, and the polyion complex is obtained by mixing the temperature-sensitive copolymer with the nucleic acid under temperature conditions equal to or lower than the lower critical solution temperature (LCST) of the temperature-sensitive copolymer.