Development of thermosensitive poly(n-isopropylacrylamide-co-((2-dimethylamino) ethyl methacrylate))-based nanoparticles for controlled drug release.

Abstract

Thermosensitive nanoparticles based on poly(N-isopropylacrylamide-co-((2-dimethylamino)ethylmethacrylate)) (poly(NIPA-co-DMAEMA)) copolymers were successfully fabricated by free radical polymerization. The lower critical solution temperature (LCST) of the synthesized nanoparticles was 41 °C and a temperature above which would cause the nanoparticles to undergo a volume phase transition from 140 to 100 nm, which could result in the expulsion of encapsulated drugs. Therefore, we used the poly(NIPA-co-DMAEMA) nanoparticles as a carrier for the controlled release of a hydrophobic anticancer agent, 7-ethyl-10-hydroxy-camptothecin (SN-38). The encapsulation efficiency and loading content of SN-38-loaded nanoparticles at an SN-38/poly(NIPA-co-DMAEMA) ratio of 1/10 (D/P = 1/10) were about 80% and 6.293%, respectively. Moreover, the release profile of SN-38-loaded nanoparticles revealed that the release rate at 42 °C (above LCST) was higher than that at 37 °C (below LCST), which demonstrated that the release of SN-38 could be controlled by increasing the temperature. The cytotoxicity of the SN-38-loaded poly(NIPA-co-DMAEMA) nanoparticles was investigated in human colon cancer cells (HT-29) to compare with the treatment of an anticancer drug, Irinotecan(®) (CPT-11). The antitumor efficacy evaluated in a C26 murine colon tumor model showed that the SN-38-loaded nanoparticles in combination with hyperthermia therapy efficiently suppressed tumor growth. The results indicate that these thermo-responsive nanoparticles are potential carriers for controlled drug delivery.

• Authors: Cheng-Liang Peng, Han-Min Tsai, Shu-Jyuan Yang, Tsai-Yueh Luo, Chia-Fu Lin, Wuu-Jyh Lin, Ming-Jium Shieh
• Journal: Nanotechnology (Nanotechnology) Vol. 22 Issue 26 Pg. 265608 (Jul 01 2011) ISSN: 1361-6528 [Electronic] England
• PMID: 21576795 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Delayed-Action Preparations
• Methacrylates
• Polymethacrylic Acids
• poly(N-isopropylacrylamide-co-((2-dimethylamino)ethylmethacrylate))
• Irinotecan
• 2-(dimethylamino)ethyl methacrylate
• Camptothecin

Topics

• Absorption (drug effects)
• Animals
• Antineoplastic Agents (pharmacology)
• Camptothecin (analogs & derivatives, pharmacology)
• Cell Death (drug effects)
• Delayed-Action Preparations
• Endocytosis (drug effects)
• Female
• Fluorescence
• HT29 Cells
• Humans
• Irinotecan
• Magnetic Resonance Spectroscopy
• Methacrylates (chemistry)
• Mice
• Mice, Inbred BALB C
• Nanoparticles (chemistry, ultrastructure)
• Nanotechnology (methods)
• Particle Size
• Polymethacrylic Acids (chemistry)
• Static Electricity
• Temperature
• Thermogravimetry