Preparation of nanoparticles of PEG-grafted poly-L-lysine for drug delivery

Drug carriers are expected to provide a controlled release and a selective targeting of drugs. At the same time, the long circulation time of carriers in blood and their degradable property are required. The secondary structure of poly-L-lysine (PLL) changed responding to pHs and temperatures among random, α -helix, and β -sheet forms. Poly(ethylene glycol) (PEG) was coupled with the backbone of PLL (mPEG-PLL graft polymers). PEG-rich graft polymers were associated to form nanoparticles spontaneously by the formation of β -sheet structures when both pHs and temperatures were raised. Nanoparticles were cross-linked with divinyl sulfone (DVS) to prevent them from dissolving. By circular dichroism (CD) spectrometry, it was found that the cross-linked nanoparticles changed their secondary structure from β -sheet to ramdom coil and thereby swelled and became soluble partially as the pH was lowered to 6.0. This suggests that cross-linked nanoparticles have an ability to release drugs in response to pH when they are taken up by cells and delivered to endosomes.