Stable micelles formed with diblock copolymers of critical micelle concentration copolymer and temperature-sensitive copolymer
AssigneeNational Tsing Hua University
InventorsGing-Ho Hsiue, Chun-Liang Lo, Sheng-Jie Lin, Hsieh-Chih Tsai
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Abstract
A novel class of mixed micelles formed with critical micelle concentration (Cmc) character's diblock copolymer, and temperature-sensitive character's diblock copolymer were disclosed. The mixed micelles possess complementary effects in adjusting external temperature shift (storage vs. body temperature) and concentration change (dilution after intravenous injection). The mixed micelles of the present invention can serve as a potential injectable drug delivery system for anticancer drugs, such as doxorubicin and many others.
Claims37
A polymeric micelle comprising a temperature-sensitive block copolymer, said temperature-sensitive block copolymer comprising a hydrophobic polymeric segment and a hydrophilic polymeric segment, wherein said hydrophobic polymeric segment is a copolymer of monomers comprising a pH-/ionic strength sensitive monomer and a temperature-sensitive monomer, wherein the polymeric micelle has a LCST lower than 37° C. at a pH value of 7-8 and has a LCST greater than 37° C. at a pH value of 6 or less than 6;
- the polymeric micelle has a polydispersity index less than 0.2;
- and the polymeric micelle forms a micellar solution in water with micellar particle sizes within 50-200 nm.
A process for preparing a polymeric micelle, which comprises the following steps:
- a) dissolving a temperature-sensitive block copolymer and optionally a Cmc block copolymer in an organic solvent, wherein said temperature-sensitive block copolymer comprising a hydrophobic polymeric segment and a hydrophilic polymeric segment, wherein said hydrophobic polymeric segment is a copolymer of monomers comprising a pH-/ionic strength sensitive monomer and a temperature-sensitive monomer, and said Cmc block copolymer comprises a hydrophobic polymeric segment and a hydrophilic polymeric segment;
- b) mixing the resulting polymer solution from step a) with an aqueous medium having a temperature higher than LCST of said temperature-sensitive block copolymer to form a micellar solution in the aqueous medium;
- and
- c) subjecting the resulting mixture from step b) to a dialysis treatment against water to replace the organic solvent in the mixture with water or subjecting the resulting mixture from step b) to a reduced pressure and/or an elevated temperature to evaporate the organic solvent from the mixture.
Dependencies are inferred from the claim text.