<p>Glucose-Sensitive Nanoparticles Based On Poly(3-Acrylamidophenylboronic Acid-Block-N-Vinylcaprolactam) For Insulin Delivery</p>

Abstract

BackgroundCompared 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.PurposeIn 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.MethodsThe 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.ResultsThe 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.ConclusionOur 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.

Nanoparticles Prepared From Pterostilbene (PTE): A New Strategy for Reducing Blood Glucose and Improving Diabetic Complications

“…It is suggested that the p(AAPBA-b-PTE) NPs can intelligently release insulin in diabetic patients. Compared with our previously prepared p(NVCLco-AAPBA) NPs [13], the addition of PTE did not damage the phenylboronic acid functional group, which had a more stable glucose sensitivity. The results of structural stability test of p(AAPBA-b-PTE) NPs shows that the particle size was relatively stable within 35 days of storage, and there was little difference in particle size.…”

“…Firstly, acrylic acid-PTE was prepared by using acryloyl chloride to endow the C = C double bond of pterostilbene (scheme 2A), so that it can be used as a part of polymer materials. P(AAPBA) was prepared according to our previously published protocol [13]. Next, as shown in scheme 1C, p(AAPBA-b-PTE) was synthesized via "one-pot" reported in our previous literature [14].…”

“…Zheng [12] et al also prepared an amphiphilic glycopolymer (p(LAMA-r-AAPBA)), which can be delivered through the nasal cavity with lower blood glucose. In previous studies, we used N-vinylcaprolactam (NVCL), Diethylene glycol dimethacrylate DEGMA , 6-O-vinylazeloyl-dgalactose(OVZG) to copolymerize with AAPBA, and successfully synthesized a variety of glucose sensitive carriers [13][14][15]. In summary of previous studies, whether polymers formed as thermosensitive monomers, pH sensitive monomers, polyaminoacids, glycolipid monomers, can make them glucose responsive through various process methods.…”

Nanoparticles prepared from pterostilbene reduce blood glucose and improve diabetes complications

“…The first step involved preparing acrylic acid-PTE by using acryloyl chloride to endow the C=C double bond of pterostilbene (Scheme 2 a), so that it could be used as a component in the polymer materials. P(AAPBA) was prepared according to our previously published protocol [ 12 ]. Next, as shown in Scheme 1 C, p(AAPBA-b-PTE) was synthesised via ‘one-pot’, as reported in our previous literature [ 13 ].…”

“…Zheng [ 11 ] et al also prepared an amphiphilic glycopolymer (p[LAMA-r-AAPBA]), which can be delivered with lower blood glucose through the nasal cavity. In previous studies, we used N-vinylcaprolactam (NVCL), diethylene glycol dimethacrylate (DEGMA) and 6-O-vinylazeloyl-d-galactose (OVZG) to copolymerise with AAPBA, with which a variety of glucose-sensitive carriers were successfully synthesised [ 12 – 14 ]. In a summary of previous studies, various formations of polymers, including thermosensitive monomers, pH-sensitive monomers, polyaminoacids, and glycolipid monomers, can be made glucose responsive through various processing methods (Summarised in Additional file 1 : Table S1).…”