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.

Characterization of temperature induced changes in liposomes coated with poly( N -isopropylacrylamide- co -methacrylic acid)

“…Polymers with thermoresponsive properties, such as poly(Nisopropylacrylamide) (PNIPAAM), are interesting for drug delivery applications as this property may be used to control drug release or to allow the drug delivery system to bind to cell surfaces at specific temperatures [24][25][26][27][28]. PNIPAAM has a lower critical solution temperature (LCST) around 32°C [29].…”

Colorectal Cancer from Molecular Pathways to Gene Therapy

“…Several efforts have been made towards identifying the genome of CRC cancer and therefore providing targeted therapy, mostly in the form of chemotherapy or inhibitors. Gene therapy in the form of molecular pathway inhibition has been proposed with the help of drug delivery systems for efficient delivery such as; the SN-38, and nanoparticles [74][75][76], liposomes [77], carbon nanotubes [78] and polymeric micelles. [79,80] Today the investigation of the various resistance mechanisms has led to the development of new drugs that can be specifically targeted as inhibitors of certain molecular pathways.…”

Physical and Chemical Strategies for Therapeutic Delivery by Using Polymeric Nanoparticles

“…Recent in vivo studies are also beginning to show some promising results to treat cancer using thermosensitive nanoparticles based on poly(N-isopropylacrylamide-co-((2-dimethylamino)ethylmethacrylate) copolymers. For instance, the chemotherapeutic drug SN-38 can be delivered using thermosensitive nanoparticles to efficiently suppress colon tumor growth when combined with hyperthermia (Peng et al, 2011). Poly(N-isopropylacrylamide)-based systems are limited by the polymer's toxicity, immunogenicity, and short blood circulation time, but these could be overcome by PEGylation or other creative designs to shield the thermosensitive portion of the nanoparticle (Zhao et al, 2011).…”