载羧甲基壳聚糖介孔硅纳米粒用于 5-氟尿嘧啶眼部给药：特性、体外与体内研究。
Mesoporous Silica Nanoparticles Coated with Carboxymethyl Chitosan for 5-Fluorouracil Ocular Delivery: Characterization, In Vitro and In Vivo Studies.
机构信息
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Nanobiotechnology Unit, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
出版信息
Molecules. 2023 Jan 27;28(3):1260. doi: 10.3390/molecules28031260.
This study investigates the development of topically applied non-invasive amino-functionalized silica nanoparticles (AMSN) and O-Carboxymethyl chitosan-coated AMSN (AMSN-CMC) for ocular delivery of 5-Fluorouracil (5-FU). Particle characterization was performed by the DLS technique (Zeta-Sizer), and structural morphology was examined by SEM and TEM. The drug encapsulation and loading were determined by the indirect method using HPLC. Physicochemical characterizations were performed by NMR, TGA, FTIR, and PXRD. In vitro release was conducted through a dialysis membrane in PBS (pH 7.4) using modified Vertical Franz diffusion cells. The mucoadhesion ability of the prepared nanoparticles was tested using the particle method by evaluating the change in zeta potential. The transcorneal permeabilities of 5-FU from AMNS-FU and AMSN-CMC-FU gel formulations were estimated through excised goat cornea and compared to that of 5-FU gel formulation. Eye irritation and ocular pharmacokinetic studies from gel formulations were evaluated in rabbit eyes. The optimum formulation of AMSN-CMC-FU was found to be nanoparticles with a particle size of 249.4 nm with a polydispersity of 0.429, encapsulation efficiency of 25.8 ± 5.8%, and drug loading capacity of 5.2 ± 1.2%. NMR spectra confirmed the coating of AMSN with the CMC layer. In addition, TGA, FTIR, and PXRD confirmed the drug loading inside the AMSN-CMC. Release profiles showed 100% of the drug was released from the 5-FU gel within 4 h, while AMSN-FU gel released 20.8% of the drug and AMSN-CMC-FU gel released around 55.6% after 4 h. AMSN-CMC-FU initially exhibited a 2.45-fold increase in transcorneal flux and apparent permeation of 5-FU compared to 5-FU gel, indicating a better corneal permeation. Higher bioavailability of AMSN-FU and AMSN-CMC-FU gel formulations was found compared to 5-FU gel in the ocular pharmacokinetic study with superior pharmacokinetics parameters of AMSN-CMC-FU gel. AMSN-CMC-FU showed 1.52- and 6.14-fold higher AUC0-inf in comparison to AMSN-FU and 5-FU gel, respectively. AMSN-CMC-FU gel and AMSN-FU gel were "minimally irritating" to rabbit eyes but showed minimal eye irritation potency in comparison to the 5 FU gel. Thus, the 5-FU loaded in AMSN-CMC gel could be used as a topical formulation for the treatment of ocular cancer.
本研究旨在开发局部应用的非侵入性氨基功能化硅纳米粒子（AMSN）和 O-羧甲基壳聚糖涂覆的 AMSN（AMSN-CMC），用于眼部传递 5-氟尿嘧啶（5-FU）。通过 DLS 技术（Zeta-Sizer）进行颗粒表征，并通过 SEM 和 TEM 检查结构形态。通过间接方法使用 HPLC 测定药物包封和载药量。通过 NMR、TGA、FTIR 和 PXRD 进行物理化学特性分析。通过改良的垂直 Franz 扩散池在 PBS（pH 7.4）中进行体外释放。通过评估 Zeta 电位的变化来测试制备的纳米粒子的粘膜粘附能力。通过比较 5-FU 凝胶制剂，通过评估角膜穿透性来估计 AMNS-FU 和 AMSN-CMC-FU 凝胶制剂中 5-FU 的透皮渗透率。通过兔眼评估凝胶制剂的眼部刺激性和眼内药代动力学研究。发现 AMSN-CMC-FU 的最佳配方是粒径为 249.4nm、多分散度为 0.429、包封效率为 25.8%±5.8%、载药量为 5.2%±1.2%的纳米粒子。NMR 谱证实了 AMSN 与 CMC 层的涂层。此外，TGA、FTIR 和 PXRD 证实了 AMSN-CMC 内的药物负载。释放曲线表明，5-FU 凝胶在 4 小时内释放了 100%的药物，而 AMSN-FU 凝胶在 4 小时后释放了 20.8%的药物，而 AMSN-CMC-FU 凝胶释放了约 55.6%。与 5-FU 凝胶相比，AMSN-CMC-FU 最初表现出 2.45 倍的角膜通量和 5-FU 的表观渗透增加，表明角膜渗透更好。与 5-FU 凝胶相比，在眼部药代动力学研究中发现 AMSN-FU 和 AMSN-CMC-FU 凝胶制剂的生物利用度更高，具有更好的药代动力学参数。与 AMSN-FU 和 5-FU 凝胶相比，AMSN-CMC-FU 凝胶的 AUC0-inf 分别高出 1.52 倍和 6.14 倍。AMSN-CMC-FU 凝胶和 AMSN-FU 凝胶对兔眼“轻度刺激”，但与 5-FU 凝胶相比，刺激强度最小。因此，负载在 AMSN-CMC 凝胶中的 5-FU 可作为眼部癌症治疗的局部制剂。
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