A Nanoparticle-Based Ophthalmic Formulation of Dexamethasone Enhances Corneal Permeability of the Drug and Prolongs Its Corneal Residence Time
A Nanoparticle-Based Ophthalmic Formulation of Dexamethasone Enhances Corneal Permeability of the Drug and Prolongs Its Corneal Residence Time
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DOI：
10.1248/bpb.b17-00137
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发表时间：
2017-07-01
影响因子：
2
通讯作者：
Shimomura, Yoshikazu
中科院分区：
文献类型：
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作者：
Nagai, Noriaki;Nakazawa, Yosuke;Shimomura, Yoshikazu
我们设计了含有地塞米松负载的固体纳米颗粒（DEXnano分散体）的眼科配方，并研究了角膜的渗透性和毒性。以0.1%地塞米松（DEX）粉末（DEX微粒）、0.026%对羟基苯甲酸甲酯（MP）、0.014%对羟基苯甲酸丙酯（PP）、0.5%甲基纤维素为原料，采用球磨法制备DEXnano分散体。DEXnano分散体的平均粒径为78 nm。采用大肠杆菌法检测DEXnano分散体的抗菌活性，并采用角膜上皮清创大鼠模型和人角膜上皮永生化细胞系HCE-T细胞评价其角膜毒性。观察了DEXnano分散体在兔角膜中的渗透情况。DEXnano分散体在制备后14d保持高度稳定。虽然DEX本身不表现出抗菌活性，但含有对羟基苯甲酸酯（MP和PP）的DEXnano分散体表现出较高的抗菌活性，与不含DEX的对羟基苯甲酸酯溶液的抗菌活性大致相等。DEXnano分散体的DEX角膜穿透率（J(c)）和平均停留时间（MRT）分别比含有DEX微粒的分散体（平均粒径为11.3 μ m）高5.1倍和1.3倍。此外，DEXnano分散体与载药体对角膜的刺激无显著差异。综上所述，我们成功制备了含有DEX固体纳米颗粒的高质量分散体，并且基于纳米颗粒的DEX眼科配方提高了药物的角膜渗透性和停留时间。DEXnano分散体在治疗眼部炎症方面可能会显示出更高的有效性。
We designed ophthalmic formulations containing dexamethasone-loaded solid nanoparticles (DEXnano dispersion), and investigated corneal permeability and toxicity. 0.1% dexamethasone (DEX) powder (DEX microparticles), 0.026% methyl p-hydroxybenzoate (MP), 0.014% propyl p-hydroxybenzoate (PP), and 0.5% methylcellulose were used, and the DEXnano dispersion was prepared by the bead mill method. The mean particle size of DEXnano dispersion was 78 nm. Antimicrobial activity of the DEXnano dispersion were measured by using Escherichia coli, and the corneal epithelium-debrided rat model and HCE-T cells (immortalized human corneal epithelial cell line) were used to estimate the corneal toxicity. The transcorneal penetration of the DEXnano dispersion were evaluated in the corneas of rabbit. The DEXnano dispersion was found to be highly stable until 14d after its preparation. Although DEX itself did not exhibit antimicrobial activity, the DEXnano dispersion containing parabens (MP and PP) showed high antimicrobial activity, approximately equal to that of the solution containing parabens without DEX. The corneal penetration rate (J(c)) and mean residence time (MRT) of DEX from the DEXnano dispersion were approximately 5.1- and 1.3-fold higher, respectively, than those of a dispersion containing DEX microparticles (mean particle size, 11.3 mu m). In addition, no significant difference was found in corneal stimulation between the vehicle and DEXnano dispersion. In conclusion, we successfully prepared high quality dispersion containing DEX solid nanoparticles, and the nanoparticle-based ophthalmic formulation of DEX enhanced the corneal permeability and residence time of the drug. It is possible that DEXnano dispersion will show increased effectiveness in treating ocular inflammation.