سنتز و مشخصه‌يابي پليمرهاي پر شاخه و كاهش سميت آن در جهت ايجاد سامانه‌ي پاسخگو به گلوكز و محاسبه‌ي ثابت تفكيك اسيدي و اتصال

Diabetes is a common metabolic disorder characterized by impaired insulin secretion an‎d/or function, leading to chronic hyperglycemia. If not properly controlled, it can result in numerous acute an‎d long-term complications. In this context, the development of smart, self-regulated insulin delivery systems based on glucose-responsive materials has attracted considerable attention as a novel therapeutic strategy. Phenylboronic acid (PBA) is one of the most widely studied glucose-responsive moieties; however, its relatively high pKa an‎d limited stability at physiological pH present significant challenges for practical applications. In this study, novel hybrid nanocarriers were synthesized based on poly(amidoamine) (PAMAM) dendrimers with a nanocrystalline cellulose core an‎d poly(propylene imine) (PPI) dendrimers with an ethylenediamine core, followed by functionalization with 4-carboxyphenylboronic acid (4-CPBA). Structural characterization of the dendrimers an‎d the modified nanocarriers was performed using FT-IR, ^1H NMR, GPC, TGA, an‎d XRD analyses, confirming successful synthesis an‎d functionalization. Determination of the acid dissociation constant (pKa) by titration an‎d spectrophotometric differential methods revealed that increasing the generation of PAMAM dendrimers led to a decrease in pKa, achieving full compatibility with physiological pH at the third generation. DLS an‎d FE-SEM analyses confirmed the appropriate glucose responsiveness of the developed nanocarriers. The insulin encapsulation efficiency of third-generation PAMAM reached 74%. The cumulative insulin release was 30% in the absence of glucose an‎d increased to 58% an‎d 60% in the presence of 1 an‎d 3 mg/mL glucose, respectively. Cytotoxicity studies demonstrated high biocompatibility of this nanocarrier up to a concentration of 200 µg/mL.Similarly, fourth-generation PPI dendrimers functionalized with PBA exhibited a significant reduction in pKa an‎d desirable responsiveness to varying glucose concentrations. The encapsulation efficiency an‎d loading capacity of insulin were calculated to be 92% an‎d 23%, respectively. In PBS at pH 7.4, insulin release increased from 26% in the absence of glucose to 82% in the presence of 3 mg/mL glucose. Cytotoxicity assays further confirmed the non-toxic nature of this nanocarrier up to 400 µg/mL after 48 hours of incubation.Overall, PBA-functionalized PAMAM an‎d PPI dendrimer-based nanocarriers demonstrated safe, effective, an‎d glucose-responsive behavior for smart insulin delivery an‎d represent promising can‎didates for improving therapeutic management of diabetes.

طيبه بهزاد , مهدي سلامي كلجاهي

محمدامين بوجاري

محمد ديناري , سميرا اقبلاغي , افسانه فخار