PREPARATION OF pH-RESPONSIVE NANOPARTICLES AND PROMOTED DELIVERY OF ANTICANCER DRUGS INTO DEEP TUMOR TISSUES AND APPLICATION THEREOF

Patent metadata

Field	Value
Publication number	US-2016367489-A1
Application number	US-201514931872-A
Country	US
Kind code	A1
Filing date	Nov 4, 2015
Priority date	Jun 22, 2015
Publication date	Dec 22, 2016
Grant date	—

Abstract

A pH-responsive nanoparticle made of a pH-responsive polymer and a poly(lactic-co-glycolic acid) by self-assembly includes a polyethylene glycol derivative and a R-Histidine derivative that are subjected to a chemical reaction to form the pH-responsive polymer, wherein the surface electric potential of the pH-responsive nanoparticle is −25 to 10 mV, such that when a pH value of the pH-responsive nanoparticle is changed from 7.4 to 5.0 depending upon an external environment, a surface zeta potential of the pH-responsive nanoparticle is converted from negative charge to positive charge.

First claim

1 . A pH-responsive nanoparticle made of a pH-responsive polymer and a poly(lactic-co-glycolic acid) by self-assembly,
wherein the pH-responsive polymer is formed by a polyethylene glycol derivative and a R-Histidine derivative through a chemical reaction; wherein the surface electric potential of the pH-responsive nanoparticle is −25 to 10 mV, such that when a pH value of the pH-responsive nanoparticle is changed from 7.4 to 5.0 depending upon an external environment, a surface zeta potential of the pH-responsive nanoparticles is converted from negative charge to positive charge; wherein the pH-responsive polymer is connected to poly(lactic-co-glycolic acid) through the polyethylene glycol derivative, and the R-Histidine derivative is selected from a group consisting of N-acetyl-Histidine, L-Histidine, D-Histidine, and 3-Methyl-L-histidine.

2 . The pH-responsive nanoparticle as claimed in claim 1 , wherein the pH-responsive polymer is formed from the conjugation of the polyethylene glycol derivative and the R-Histidine derivative via an esterification.

3 . The pH-responsive nanoparticle as claimed in claim 2 , wherein the polyethylene glycol derivative is Vitamin E TPGS or DSPE-PEG.

4 . (canceled)

5 . The pH-responsive nanoparticle as claimed in claim 1 , wherein the pH-responsive nanoparticle includes a hydrophilic shell and a hydrophobic core, and the hydrophilic shell is located at an outer side of the hydrophobic core.

6 . The pH-responsive nanoparticle as claimed in claim 5 , wherein the hydrophobic core further lade an anticancer drug, developer, photothermal agent, nano-metal particle, or combinations thereof.

7 . A pH-responsive nanoparticle adapted for preparation of a delivery system capable of promoting the tumor accumulation of anticancer drug and an application of a deep tumor penetration of drug, comprising:
(a) a polyethylene glycol derivative and a R-Histidine derivative subjected to a chemical reaction to form a pH-responsive polymer; and (b) the pH-responsive polymer and a poly(lactic-co-glycolic acid) underwent a self-assembly process to form the pH-responsive nanoparticles, wherein a surface zeta potential of the pH-responsive nanoparticles under different pH conditions is −25 to 10 mV; wherein the pH-responsive polymer is connected to poly(lactic-co-glycolic acid) through the polyethylene glycol derivative, and the R-Histidine derivative is selected from a group consisting of N-acetyl-Histidine, L-Histidine, D-Histidine, and 3-Methyl-L-histidine.

8 . The pH-responsive nanoparticle adapted for preparation of a delivery system capable of promoting the tumor accumulation of anticancer drug and an application of a deep tumor penetration of drug, as claimed in claim 7 , wherein the polyethylene glycol derivative is Vitamin E TPGS or DSPE-PEG.

9 . (canceled)

10 . The pH-responsive nanoparticle adapted for preparation of a delivery system capable of promoting the tumor accumulation of anticancer drug and an application of a deep tumor penetration of drug, as claimed in claim 7 , wherein the pH-responsive nanoparticle includes a hydrophilic shell and a hydrophobic core, and the hydrophilic shell is located at an outer side of the hydrophobic core.

11 . The pH-responsive nanoparticle adapted for preparation of a delivery system capable of promoting the tumor accumulation of anticancer drug and an application of a deep tumor penetration of drug, as claimed in claim 10 , wherein the hydrophobic core further loads an anticancer drug, developer, photothermal agent, nano-metal particle, or combinations thereof.

Assignees

• Nat Univ Tsing Hua

Inventors

• Chiu Hsin-Cheng
• Chiang Wen-Hsuan
• Hung Chia-Chian
• Yu ting-wei

Classifications

• G01N33/84

  involving inorganic compounds or pH · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61K9/5153 Primary

  Polyesters, e.g. poly(lactide-co-glycolide) · CPC title

• A61K41/0052

  Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title