Abstract: AimTo prepare recombinant human tumor necrosis factor-α (rHuTNF-α)-loaded stealth nanoparticles with different PEG chain lengths and sizes, and investigate the stability of nanoparticle suspensions. MethodsThe poly(MePEG cyanoacrylate-co-hexadecyl cyanoacrylate) (MePEG-PHDCA) and poly(hexadecyl cyanoacrylate) (PHDCA) were synthesized and characterized with Fourier transform infrared spectrum (FTIR), ¹HNMR, ¹³CNMR and gel permeation chromatography (GPC). Uniform design was used to optimize the entrapment efficiency. The nanoparticle suspensions were stored at 2-8 ℃ for 4 weeks, and the particle size evolution was studied. ResultsFTIR, ¹HNMR and ¹³CNMR were consistent with the structures of MePEG-PHDCA and PHDCA whose polydispersity indexes were all less than 1.1, indicating narrow distributions. The entrapment efficiency of all nanoparticles was satisfactory. The three different mean diameters of MePEG-PHDCA and PHDCA nanoparticles were about 80 nm, 170 nm and 240 nm, separately. The nanoparticle suspensions maintained their sizes at 2-8 ℃ for 4 weeks ConclusionMePEG-PHDCA with three different molecular weight MePEG and PHDCA were synthesized successfully. There are negligible aggregations and bulk or surface erosion as for both stealth MePEG-PHDCA and conventional PHDCA nanoparticles in distilled water.