The aim of this work was to design a novel ocular delivery carrier based on liposomes loaded with azithromycin (AZM) for the treatment of dry eye (DE) disease. To improve the drug loading efficiency, an AZM–cholesteryl hemisuccinate (CHEMS) ion pair (ACIP) was first prepared, and the successful formation of the ACIP was characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRD), which demonstrated a stable interaction between CHEMS and AZM. The ACIP-loaded liposome (ACIP-Lip) appeared as spherical particles under TEM, with a uniform particle size of 60 ± 2 nm and zeta potential of −20.3 ± 4.6 mV. The entrapment efficiency (EE) and drug loading (DL) of ACIP-Lip were greatly improved to 95.6 ± 2.0 and 9.2 ± 0.7%, respectively, which was attributed to the enhanced loading capacity of the liposomes through use of the ion pair and addition of MCT. ACIP-Lip also exhibited a high stability during a 3 month storage period at both 4 and 25 °C. In vitro release of AZM from ACIP-Lip was pH-dependent, with a more rapid release at pH 6.0 than at pH 7.4, which is beneficial for ocular therapy. Furthermore, the corneal permeation of AZM was enhanced by ACIP-Lip, demonstrating an apparent permeability coefficient (P_app × 10⁶) of 8.92 ± 0.56 cm/s, which was approximately 2-fold greater that of the AZM solution. Finally, an in vivo pharmacodynamical study showed that the essential symptoms of DE rats were significantly improved by ACIP-Lip, as it was highly efficient and superior compared to hyaluronic acid sodium eye drops available on the market. Hence, ACIP-Lip is a promising formulation for DE treatment.

中文翻译：

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阿奇霉素离子对在脂质体中的包裹，以增强干眼的眼部递送和治疗功效

这项工作的目的是设计一种基于载有阿奇霉素（AZM）的脂质体的新型眼部递送载体，以治疗干眼症（DE）。为了提高载药效率，首先制备了AZM-胆固醇半琥珀酸酯（CHEMS）离子对（ACIP），并通过傅里叶变换红外光谱（FTIR），差示扫描量热法（DSC）和质谱分析了ACIP的成功形成。 X射线粉末衍射（XRD），表明CHEMS与AZM之间存在稳定的相互作用。载有ACIP的脂质体（ACIP-Lip）在TEM下显示为球形颗粒，粒径均匀，为60±2 nm，ζ电位为-20.3±4.6 mV。ACIP-Lip的包封率（EE）和载药量（DL）分别大大提高到95.6±2.0和9.2±0.7％，这归因于通过使用离子对和添加MCT，脂质体的负载能力增强。ACIP-Lip在4°C和25°C下三个月的存储期内也显示出很高的稳定性。AZM从ACIP-Lip的体外释放是pH依赖性的，在pH 6.0时比在pH 7.4时释放更快，这对眼部治疗非常有益。此外，ACIP-Lip可增强AZM的角膜渗透性，表明其表观渗透系数（P _app ×10 ⁶）为8.92±0.56 cm / s，约为AZM解决方案的2倍。最后，一项体内药效学研究表明，ACIP-Lip可显着改善DE大鼠的基本症状，因为与市场上出售的透明质酸钠滴眼剂相比，DEIP的高效性和优越性。因此，ACIP-Lip是用于DE治疗的有前途的制剂。