The clinical utility of siRNA therapy has been hampered due to poor cell penetration, nonspecific effects, rapid degradation,\nand short half-life. We herewith proposed the formulation development of STAT6 siRNA (S6S) nanotherapeutic agent by\nencapsulating them within gelatin nanocarriers (GNC). The prepared nanoformulation was characterized for size, charge, loading\nefficiency, release kinetics, stability, cytotoxicity, and gene silencing assay. The stability of S6S-GNC was also assessed under\nconditions of varying pH, serum level, and using electrophoretic assays. In vitro cytotoxicity performance was evaluated in human\nadenocarcinoma A549 cells following MTT assay.The developed formulation resulted in an average particle size, surface charge,\nand encapsulation efficiency as 70�±6.5 nm, +10�±1.5mV, and 85�±4.0%, respectively. S6S-GNC showed an insignificant (P< 0.05)\nchange in the size and charge in the presence of buffer solutions (pH 6.4 to 8.4) and FBS (10% v/v). A549 cells were treated with\nnative S6S, S6S-lipofectamine, placebo-GNC, and S6S-GNC using untreated cells as a control. It was observed that cell viability\nwas decreased significantly with S6S-GNC by 55 �± 4.1% (P < 0.001) compared to native S6S (2.0 �± 0.55%) and S6S-lipofectamine\ncomplex (40 �± 3.1%). This investigation infers that gelatin polymer-based nanocarriers are a robust, stable, and biocompatible\nstrategy for the delivery of siRNA.
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