Self‐assembled, fluorescent polymeric micelles of a graft copolymer containing carbazole for thermo‐controlled drug delivery in vitro

Abstract

A novel thermosensitive amphiphilic graft copolymer PNIPAAm-g-PCbzEA appending carbazole group was successfully designed and synthesized by the free radical copolymerization of N-isopropylacrylamide with hydrophobic precursor polymers of vinyl-functionalized poly(2-(N-carbazolyl)ethyl acrylate) (PCbzEA) in DMF. The PNIPAAm-g-PCbzEA copolymer was characterized by FTIR, (1)H NMR, GPC analysis, UV-vis spectroscopy and fluorescence spectroscopy. The TEM observation shows that the graft copolymer may self-assemble into polymeric micelles exhibiting a nanospheric morphology within a narrow size range of 30-60 nm in aqueous solution. From the (1)H NMR and FTIR analysis, the polymer micelles are composed of hydrophobic PCbzEA segments as the cores and the hydrophilic PNIPAAm segements as outer shells. The resulting micelles exhibited the temperature sensitivity with a lower critical solution temperature (LCST) of 31.5 degrees C and a critical micelle concentration (CMC) of 12.9 mg/L in water. In the study of drug release, an "on-off" drug release profile was found in response to stepwise temperature changes between 20 and 40 degrees C. The cytotoxicity assays for vero cells shows good biocompatibility of the graft copolymer in vitro.

Self-assembling materials for therapeutic delivery

“…Importantly, the long induction time ensures sufficient time for the micelles to accumulate in the small vasculature before the drug is released. Other micelles have been designed from diblock copolymers with release profiles that are responsive to changes in pH [75–78] and temperature [61,79,80]. These systems have been recently reviewed [81,82].…”

Thermoresponsive Polymer Colloids for Drug Delivery and Cancer Therapy

“…Conversely, Liu et al observed reduced methotrexate release above the LCST for micelles formed from poly{NIPAM ‐graft‐ poly[2‐( N ‐carbazolyl)ethyl acrylate]}. The authors attributed the reduced release above the LCST to the barrier produced by the collapsed poly(NIPAM) shell 30…”

Self-assembled micellar nanoparticles of a novel star copolymer for thermo and pH dual-responsive drug release

“…As our previously work [22] described, steady-state fluorescence spectra were obtained on a Shimadzu RF-5301PC spectrometer (Japan). Pyrene was used as a hydrophobic fluorescent probe.…”

“…Over the last several years, we [22] and others [23][24][25][26][27][28][29] have investigated thermo-responsive polymeric micelles based on PNIPAAm. Yokoyama et al [23] reported polymeric micelles com- posed of thermo-responsive poly(NIPAAm-co-DMAAm) as hydrophilic blocks and biodegradable poly(d,l-lactide), poly(ε-caprolactone) or poly(d,l-lactide-co-ε-caprolactone) as hydrophobic blocks, which demonstrated thermo-responsive release of the incorporated anticancer drug, doxorubicin.…”