Studies On Biomacromolecule Capsules:Synthesis,Properties And Glucose-Triggered Insulin Delivery

Diabetics is one of the most serious diseases that affect human health. The conventional treatment need parenteral injection of insulin multiple daily to maintain the normoglycemia, which might cause overdose and bring some side effects. Thus, it is very important and necessary to develop a system that controlled release insulin with the glucose concentration. Phenylboronic acid and derivatives that conjugate with diol units to form a reversible ester bond could be combines with blood glucose monitoring, achieving self-adminstration of insulin releasing with a tight control of blood glucose. Therefore, the insulin controlled release carrier base on phenylboric acid has a theoretical significance for the effective treatment of diabetes. For the purpose of improving the stability of the carrier, enhancing the glucose sensitivity and well self-regulating release of insulin, biomacromolecule capsules contained phenylboronic acid and competitive prope rties were fabricated based on layer by layer(LBL) assembly. The stability of capsules was crosslinked via physical and chemical methods. The system with the property of glucose monitoring is expected to be achieve the self-adminstration of insulin releasing depending on the glucose concentration. I. Sodium Alginate/C hitosan O ligosaccharide-g-Phenylboronic Acid(Alg/CS-g-CPBAm)n Biomacromolecule Capsules: Synthesis, Properties and Glucose- Triggered Insulin DeliveryChitosan oligosaccharide-g-phenylboronic acid(CS-g-CPBA) was synthesized by grafting 3-carboxphenylboronic acid(CPBA) to chitosan oligosaccharide(CS), which has glucose-responsive property providing the carry possibility to control insulin release. Then, biomacromolecule microspheres(Alg/CS-g-CPBAm)n@SiO2 were prepared using functionalized silica microspheres as templates by layer-by-layer processes of Sodium alginate(Alg) and CS-g-CPBAm via electrostatic interaction. The(Alg/CS-g-CPBAm)n capsules with multi- layers were obtained by removing the SiO2 templates. Capsules can be crosslinked to improve the stability by chelating Ca2+ particles. Insulin was encapsulated in the capsules, and encapsulation efficiency was more than 61±2 %. Sizes and morphologies of biomacromolecule capsules were characterized by dynamic light scattering(DLS), scanning electron micrographs(SEM) and transmission electron microscope(TEM). The results showed that the(Alg/CS-g-CPBAm)n capsules had a good stability when it increased the number of the layers. Moreover, the stability of capsules can be improved by cross-linked with Ca2+ particles. The size of these capsules increased rapidly with increasing the glucose concentration, due to the swollen of the capsules. Cumulative release of insulin was observed from the capsules after exposed in glucose solutions with various levels. The released amount of insulin increased with incubation in glucose without Ca2+, because the diameter of the capsules diameter increased sharply and internal loose. However, the released amount of insulin dropped off after cross-linked with Ca2+ particles, which was induced by lower responsiveness of Glu and increase the inner layer tight relatively. The(Alg/CS-g-CPBAm)n capsules have the biocompatibility which was confirmed by cell viability treated with mouse embryonic fibroblast through the method of MTT. II. Poly(γ-glutamic acid)-g-Aminophenylboronic acid)/Galactosed C hitosan O ligosaccharide(γ-PGA-g-APBA/GC)5 Biomacromolecule Capsules: Synthesis, Properties and GlucoseTriggered Insulin DeliveryPoly(γ-glutamic acid)-g-3-aminophenylboronic acid)(γ-PGA-g-APBA) and galactosed chitosan oligosaccharide(GC) were synthesized by grafting APBA and lactobionic acid(LA) to poly(γ-glutamic acid)(γ-PGA) and chitosan oligosaccharide(CS), respectively. Then, biomacromolecule microspheres(γ-PGA-g-APBA/GC)5@SiO2 were prepared using functionalized silica microspheres as templates by layer-by- layer processes of GC and γ-PGA-g-APBA via electrostatic interaction.(γ-PGA-g-APBA/GC)5 capsules with multi- layers were obtained by removing SiO2 templates. Insulin was encapsulated in the capsules, and encapsulation efficiency was more than 59±2 %. Size and morphology of the particles and capsules were investigated by DLS, SEM and TEM.(γ-PGA-g-APBA/GC)5 capsules showed a good glucose-responsive property. The size of these capsules increased with increasing the glucose concentration, due to the swollen of the capsules. The capsules could be dissociated at high glucose concentration, due to the broken of the cross linking bonds between APBA and LA by the competitive react of the APBA with glucose. The encapsulated insulin could be self-regulated released from the capsules depending on the glucose level and APBA composition. The released amount of insulin increased w ith incubation in higher glucose concentration, while decreased with higher APBA composition. Moreover, two more On-Off regulation of insulin release from the(γ-PGA-g-APBA/GC)5 capsules could be triggered with a synchronizing and wavering change of the external glucose concentration, where as the capsules without the LA functional groups did not showed. Furthermore,(γ-PGA-g-APBA/GC)5 capsules have the biocompatibility which was confirmed by cell viability treated with mouse embryonic fibroblast through the method of MTT.These biomacromolecule capsules with good stability, glucose-response and controlled insulin delivery are expected to be used to the fields of the diagnosis glucose concentration and insulin release.