Thermoresponsive and biodegradable linear-dendritic nanoparticles containing poly( N-isopropylacrylamide), poly(l-lactic acid), and poly(l-lysine) dendrons were investigated for sustained release of nerve growth factor (NGF) in response to temperature change. The nanoparticles and their degradants were not cytotoxic to neuron-like PC12 cells for at least one month. The nanoparticles were preferentially taken up by PC12 cells 6-13-times more at temperatures above (37 °C) than below (25 °C) the lower critical solution temperature of the nanoparticles. NGF could be loaded into the nanoparticles in aqueous solution and slowly released from the nanoparticles for 12 and 33 days at 25 and 37 °C, respectively. The released NGF was biologically active by promoting neurite outgrowth of PC12 cells. This work demonstrates a new concept of using thermoresponsive and biodegradable linear-dendritic nanoparticles for thermally targeted and sustained release of NGF and other protein drugs for the treatment of Alzheimer's disease and other neurological disorders.
Keywords: cellular uptake; linear−dendritic nanoparticles; nerve growth factor; neurite outgrowth; sustained release; thermoresponsive and biodegradable.