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Yan Fang,1 Xiaojie Lin,2 Xuechao Jin,2 Dongjuan Yang,2 Shan Gao,2 Kai Shi,2 Mingshi Yang1,3 1Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, Shenyang 117004, People’s Republic of China; 3Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen O DK-2100, DenmarkCorrespondence: Kai Shi; Mingshi Yang Email shikai@syphu.edu.cn; mingshi.yang@sund.ku.dkBackground: PEI is currently the most used non-viral gene carrier and the transfection efficiency is closely related to the molecular weight; however, the prominent problem is that the cytotoxicity increased with the molecular weight.Methods: A novel redox responsive biodegradable diselenide cross-linked polymer (dPSP) was designed to enhance gene expression. ICG-pEGFP-TRAIL/dPSP nanoparticles with high drug loading are prepared, which have redox sensitivity and plasmid protection. The transfection efficiency of dPSP nanoparticle was evaluated in vitro.Results: The plasmid was compressed by 100% at the N/P ratio of 16, and the particle size was less than 100 nm. When explored onto high concentrations of GSH/H2O2, dPSP4 degraded into small molecular weight cationic substances with low cytotoxicity rapidly. Singlet oxygen (1O2) was produced when indocyanine green (ICG) was irradiated by near-infrared laser irradiation (NIR) to promote oxidative degradation of dPSP4 nanoparticles. Under the stimulation of NIR 808 and redox agent, the particle size and PDI of ICG-pDNA/dPSP nanoparticle increased significantly.Conclusion: Compared with gene therapy alone, co-transportation of dPSP4 nanoparticle with ICG and pEGFP-TRAIL had better antitumor effect. Diselenide-crosslinked polyspermine had a promising prospect on gene delivery and preparation of multifunctional anti-tumor carrier.Keywords: diselenide, polysper

Yan Fang,1 Xiaojie Lin,2 Xuechao Jin,2 Dongjuan Yang,2 Shan Gao,2 Kai Shi,2 Mingshi Yang1,3 1Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, Shenyang 117004, People’s Republic of China; 3Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen O DK-2100, DenmarkCorrespondence: Kai Shi; Mingshi Yang Email shikai@syphu.edu.cn; mingshi.yang@sund.ku.dkBackground: PEI is currently the most used non-viral gene carrier and the transfection efficiency is closely related to the molecular weight; however, the prominent problem is that the cytotoxicity increased with the molecular weight.Methods: A novel redox responsive biodegradable diselenide cross-linked polymer (dPSP) was designed to enhance gene expression. ICG-pEGFP-TRAIL/dPSP nanoparticles with high drug loading are prepared, which have redox sensitivity and plasmid protection. The transfection efficiency of dPSP nanoparticle was evaluated in vitro.Results: The plasmid was compressed by 100% at the N/P ratio of 16, and the particle size was less than 100 nm. When explored onto high concentrations of GSH/H2O2, dPSP4 degraded into small molecular weight cationic substances with low cytotoxicity rapidly. Singlet oxygen (1O2) was produced when indocyanine green (ICG) was irradiated by near-infrared laser irradiation (NIR) to promote oxidative degradation of dPSP4 nanoparticles. Under the stimulation of NIR 808 and redox agent, the particle size and PDI of ICG-pDNA/dPSP nanoparticle increased significantly.Conclusion: Compared with gene therapy alone, co-transportation of dPSP4 nanoparticle with ICG and pEGFP-TRAIL had better antitumor effect. Diselenide-crosslinked polyspermine had a promising prospect on gene delivery and preparation of multifunctional anti-tumor carrier.Keywords: diselenide, polysper

Background: PEI is currently the most used non-viral gene carrier and the transfection efficiency is closely related to the molecular weight; however, the prominent problem is that the cytotoxicity increased with the molecular weight. Methods: A novel redox responsive biodegradable diselenide cross-linked polymer (dPSP) was designed to enhance gene expression. ICG-pEGFP-TRAIL/dPSP nanoparticles with high drug loading are prepared, which have redox sensitivity and plasmid protection. The trans-fection efficiency of dPSP nanoparticle was evaluated in vitro. Results: The plasmid was compressed by 100% at the N/P ratio of 16, and the particle size was less than 100 nm. When explored onto high concentrations of GSH/H2O2, dPSP4 degraded into small molecular weight cationic substances with low cytotoxicity rapidly. Singlet oxygen (1O2) was produced when indocyanine green (ICG) was irradiated by near-infrared laser irradiation (NIR) to promote oxidative degradation of dPSP4 nanoparticles. Under the stimulation of NIR 808 and redox agent, the particle size and PDI of ICG-pDNA /dPSP nanoparticle increased significantly. Conclusion: Compared with gene therapy alone, co-transportation of dPSP4 nanoparticle with ICG and pEGFP-TRAIL had better antitumor effect. Diselenide-crosslinked polysper-mine had a promising prospect on gene delivery and preparation of multifunctional anti-tumor carrier.

Background: PEI is currently the most used non-viral gene carrier and the transfection efficiency is closely related to the molecular weight; however, the prominent problem is that the cytotoxicity increased with the molecular weight. Methods: A novel redox responsive biodegradable diselenide cross-linked polymer (dPSP) was designed to enhance gene expression. ICG-pEGFP-TRAIL/dPSP nanoparticles with high drug loading are prepared, which have redox sensitivity and plasmid protection. The trans-fection efficiency of dPSP nanoparticle was evaluated in vitro. Results: The plasmid was compressed by 100% at the N/P ratio of 16, and the particle size was less than 100 nm. When explored onto high concentrations of GSH/H2O2, dPSP4 degraded into small molecular weight cationic substances with low cytotoxicity rapidly. Singlet oxygen (1O2) was produced when indocyanine green (ICG) was irradiated by near-infrared laser irradiation (NIR) to promote oxidative degradation of dPSP4 nanoparticles. Under the stimulation of NIR 808 and redox agent, the particle size and PDI of ICG-pDNA /dPSP nanoparticle increased significantly. Conclusion: Compared with gene therapy alone, co-transportation of dPSP4 nanoparticle with ICG and pEGFP-TRAIL had better antitumor effect. Diselenide-crosslinked polysper-mine had a promising prospect on gene delivery and preparation of multifunctional anti-tumor carrier.

Gastrointestinal responsive polymeric nanospheres (NPs) based on hydroxypropyl methylcellulose phthalate were prepared using spontaneous emulsification solvent diffusion method for improved oral administration of insulin. The NPs prepared under optimized conditions have an encapsulation efficiency of 90% and a particle size of about 200 nm. In vitro drug release experiments demonstrated that the NPs exhibited a gradient release profile of loaded drug when the pH value gradually increased from 3.0 to 7.4. Enzyme resistance experiments showed that under simulated gastrointestinal conditions, the NPs protected more than 60% of the drug from being degraded by trypsin. The oral hypoglycemic experiments revealed that insulin-loaded NPs could significantly reduce blood glucose levels in diabetic rats with a relative bioavailability of 8.6%. Ex vivo imaging investigation of rat tissues showed that the drug-loaded NPs could promote the absorption of insulin in the ileum and colon. The work described here suggests that the gastrointestinal responsive polymeric NPs may be promising candidates for improving gastrointestinal tract delivery of hydrophilic biomacromolecules. Accordingly, the results indicated that hydroxypropyl methylcellulose phthalate NPs with gastrointestinal stimuli responsiveness could be a promising candidate for oral insulin delivery.