Bruno Sebastián G, Martínez Sofía M, Costa Gobbato Camila, Quinteros Daniela A, Alaimo Agustina, Pérez Oscar E
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina.
Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales-Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIBICEN-CONICET), Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina.
Pharmaceutics. 2025 Mar 27;17(4):424. doi: 10.3390/pharmaceutics17040424.
: Folic acid (FA) is essential for cellular functions but has limited ocular bioavailability, restricting its therapeutic effectiveness. : To develop chitosan (CS)-based nanogels (NGs) for FA transport and release, with corneal permeation evaluation. : NGs' hydrodynamic diameter (Ho) and polydispersity index (PdI) were determined using dynamic light scattering (DLS). CS-FA interaction was confirmed by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) was applied for the dehydrated material characterization. Scanning electron microscopy (SEM) was used to evaluate the NGs ultraestructure. In vitro drug release studies were performed using a modified Franz diffusion cell, and the release profile was fitted to obtain kinetics parameters. Mucoadhesion properties were evaluated through ζ-potential measurements. Ex vivo corneal permeation studies were conducted in rabbit corneas to compare the permeability of FA contained in NGs. : NGs presented a Ho of 312.4 ± 8.2 nm and a PdI of 0.28 ± 0.04. SEM imaging revealed spherical morphologies with minor variations in size and shape induced by FA. Lyophilized and resuspended NGs exhibited a 6.8% increase in Ho and a PdI rise to 0.42, indicating slight aggregation. In vitro drug release studies demonstrated sustained FA release, as determined by the Higuchi model. Mucoadhesion studies showed a decrease in ζ-potential from +36.9 to +18.1 mV, confirming electrostatic interactions with mucin. Ex vivo corneal permeation studies indicated that encapsulated FA permeated 2.6 times slower than free FA, suggesting sustained release. : our findings demonstrate the potential of nanostructures in the form of NGs to enhance FA-loaded ocular delivery and bioavailability.
叶酸（FA）对细胞功能至关重要，但其眼部生物利用度有限，限制了其治疗效果。为开发用于FA运输和释放的基于壳聚糖（CS）的纳米凝胶（NGs），并进行角膜渗透评估。使用动态光散射（DLS）测定NGs的流体动力学直径（Ho）和多分散指数（PdI）。通过傅里叶变换红外（FTIR）光谱确认CS - FA相互作用，应用差示扫描量热法（DSC）和热重分析（TGA）对脱水材料进行表征。使用扫描电子显微镜（SEM）评估NGs的超微结构。使用改良的弗兰兹扩散池进行体外药物释放研究，并拟合释放曲线以获得动力学参数。通过ζ电位测量评估粘膜粘附特性。在兔角膜上进行离体角膜渗透研究，以比较NGs中所含FA的渗透性。NGs的Ho为312.4±8.2 nm，PdI为0.28±0.04。SEM成像显示球形形态，FA引起大小和形状的微小变化。冻干并重悬的NGs的Ho增加6.8%，PdI升至0.42，表明有轻微聚集。体外药物释放研究表明FA持续释放，由Higuchi模型确定。粘膜粘附研究表明ζ电位从+36.9 mV降至+18.1 mV，证实与粘蛋白的静电相互作用。离体角膜渗透研究表明，包封的FA渗透速度比游离FA慢2.6倍，表明有持续释放。我们的研究结果证明了NGs形式的纳米结构在增强载FA眼部递送和生物利用度方面的潜力。
