PMID- 31632018 OWN - NLM STAT- MEDLINE DCOM- 20191216 LR - 20231014 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 14 DP - 2019 TI - Glucose-Sensitive Nanoparticles Based On Poly(3-Acrylamidophenylboronic Acid-Block-N-Vinylcaprolactam) For Insulin Delivery. PG - 8059-8072 LID - 10.2147/IJN.S220936 [doi] AB - BACKGROUND: Compared with random copolymers, block copolymerization is easier to prepare for nanoparticles with core-shell structure, and they will have better glucose sensitivity and higher insulin loading. PURPOSE: In our study, insulin-loaded poly (3-acrylamidophenylboronic acid-block-N-vinyl caprolactam) p(AAPBA-b-NVCL) nanoparticles were successfully prepared and were glucose-sensitive, which could effectively lower the blood sugar levels within 72 hrs. METHODS: The polymer of p(AAPBA-b-NVCL) was produced by reversible addition-fragmentation chain transfer polymerization based on different ratios of 3-acrylamidophenylboronic acid (AAPBA) and N-vinylcaprolactam (NVCL), and its structure was discussed by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance . Next, the polymer was manufactured into the nanoparticles, and the characteristics of nanoparticles were detected by dynamic light scattering, lower critical solution temperature, and transmission electron microscopy. After that, the cell and animal toxicity of nanoparticles were also investigated. RESULTS: The results demonstrated that p(AAPBA-b-NVCL) was successfully synthesized, and can be easily self-assembled to form nanoparticles. The new nanoparticles included monodisperse submicron particles, with the size of the nanoparticle ranged between 150 and 300nm and are glucose- and temperature-sensitive. Meanwhile, insulin can be easily loaded by p(AAPBA-b-NVCL) nanoparticles and an effective sustained release of insulin was observed when the nanoparticles were placed in physiological saline. Besides, MTT assay revealed that cell viability was more than 80%, and mice demonstrated no negative impact on blood biochemistry and heart, liver, spleen, lung, and kidney after intraperitoneal injection of 10 mg/kg/d of nanoparticles. This suggested that the nanoparticles were low-toxic to both cells and animals. Moreover, they could lower the blood sugar level within 72h. CONCLUSION: Our research suggested that these p(AAPBA-b-NVCL) nanoparticles might have the potential to be applied in a delivery system for insulin or other hypoglycemic proteins. CI - (c) 2019 Wu et al. FAU - Wu, Jun-Zi AU - Wu JZ AD - Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, School of Basic Medical, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, People's Republic of China. FAU - Yang, Yuqing AU - Yang Y AD - Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, School of Basic Medical, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, People's Republic of China. FAU - Li, Shude AU - Li S AD - Department of Biochemistry and Molecular Biology, College of Basic Medicine, Kunming Medical University, Kunming, Yunnan 650500, People's Republic of China. FAU - Shi, Anhua AU - Shi A AD - Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, School of Basic Medical, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, People's Republic of China. FAU - Song, Bo AU - Song B AD - Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, School of Basic Medical, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, People's Republic of China. FAU - Niu, Shiwei AU - Niu S AD - Department of Biotechnology, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. FAU - Chen, WenHui AU - Chen W AD - Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, School of Basic Medical, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, People's Republic of China. FAU - Yao, Zheng AU - Yao Z AD - Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, School of Basic Medical, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, People's Republic of China. LA - eng PT - Journal Article DEP - 20191004 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (Acrylamides) RN - 0 (Blood Glucose) RN - 0 (Boronic Acids) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (poly(acrylamidophenylboronicacid)) RN - 6879X594Z8 (Caprolactam) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Acrylamides/chemical synthesis/*chemistry MH - Animals MH - Blood Glucose/metabolism MH - Boronic Acids/chemical synthesis/*chemistry MH - Caprolactam/analogs & derivatives/chemical synthesis/*chemistry MH - Cell Survival/drug effects MH - *Drug Delivery Systems MH - Female MH - Glucose/*analysis MH - Hydrodynamics MH - Hydrogen-Ion Concentration MH - Hypoglycemic Agents/administration & dosage/pharmacology MH - Insulin/*administration & dosage MH - Male MH - Mice MH - NIH 3T3 Cells MH - Nanoparticles/*chemistry/ultrastructure MH - Proton Magnetic Resonance Spectroscopy MH - Spectroscopy, Fourier Transform Infrared MH - Static Electricity MH - Temperature PMC - PMC6781948 OTO - NOTNLM OT - 3-acrylamidophenylboronic acid OT - AAPBA OT - N-vinylcaprolactam OT - NVCL OT - glucose-sensitive OT - nanoparticles OT - temperature-sensitive COIS- The authors report no conflicts of interest in this work. EDAT- 2019/10/22 06:00 MHDA- 2019/12/18 06:00 PMCR- 2019/10/04 CRDT- 2019/10/22 06:00 PHST- 2019/06/26 00:00 [received] PHST- 2019/09/11 00:00 [accepted] PHST- 2019/10/22 06:00 [entrez] PHST- 2019/10/22 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/10/04 00:00 [pmc-release] AID - 220936 [pii] AID - 10.2147/IJN.S220936 [doi] PST - epublish SO - Int J Nanomedicine. 2019 Oct 4;14:8059-8072. doi: 10.2147/IJN.S220936. eCollection 2019.