Thermally sensitive micelles self-assembled from poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(D,L-lactide-co-glycolide) for controlled delivery of paclitaxel

Mol Biosyst. 2005 Jul;1(2):158-65. doi: 10.1039/b501756b. Epub 2005 Jun 9.

Abstract

Thermally sensitive micelles self-assembled from poly(N-isopropylacrylamide-co- N,N-dimethylacrylamide)-b-poly(d,l-lactide-co-glycolide)[P(NIPAAm-co-DMAAm)-b-PLGA] are fabricated and used as a carrier for the controlled delivery of paclitaxel. Paclitaxel is efficiently loaded into the micelles by a membrane dialysis method. The lower critical solution temperature (LCST) of the micelles is 39.0 degrees C in PBS. Encapsulation efficiency and loading level of paclitaxel are affected by the initial loading level of paclitaxel, fabrication temperature and polymer composition. The blank and paclitaxel-loaded micelles are characterized by particle size analysis (DLS), morphology (TEM and AFM) and paclitaxel distribution (NMR, DSC and WAXRD). The micelles are spherical in shape, having an average size less than 130 nm. Paclitaxel is molecularly distributed within the core of micelles. Sustained release of paclitaxel is achieved, which is much faster at a temperature above the LCST than at the normal body temperature (37 degrees C). Cytotoxicity of free paclitaxel and paclitaxel-loaded micelles against a human breast carcinoma cell line (MDA-MB-435S) is studied at different temperatures. The cytotoxicity of the paclitaxol-loaded micelles is greater as compared to free paclitaxel. Enhanced cytotoxicity is achieved by the paclitaxol-loaded micelles when the environmental temperature increases slightly above the LCST. Paclitaxel-loaded P(NIPAAm-co-DMAAm)-b-PLGA micelles may provide a good formulation for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / chemistry
  • Acrylic Resins / chemistry
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Delayed-Action Preparations / chemistry*
  • Delayed-Action Preparations / pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • Lactic Acid / chemistry
  • Magnetic Resonance Spectroscopy
  • Micelles*
  • Microscopy, Atomic Force
  • Microscopy, Electron, Transmission
  • Paclitaxel / chemistry*
  • Paclitaxel / pharmacology
  • Particle Size
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemistry*
  • Temperature

Substances

  • Acrylamides
  • Acrylic Resins
  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Micelles
  • Polymers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • poly-N-isopropylacrylamide
  • Polyglycolic Acid
  • Lactic Acid
  • N,N-dimethylacrylamide
  • Paclitaxel