Lee Jong-Ju, Choi Minji, Jeon Yuim, Khanal Dipesh, Lee Juseung, Kim Dowoong, Chan Hak-Kim, Hwang Sung-Joo
College of Pharmacy & Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon, 21983, Republic of Korea.
Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, NSW 2006, Australia.
Int J Pharm. 2025 Mar 15;672:125314. doi: 10.1016/j.ijpharm.2025.125314. Epub 2025 Feb 3.
This study investigates the physicochemical transformation of ciprofloxacin (CIP) through hydrophobic ion pairing with five counter ions-sodium oleate, sodium laurate, sodium caprate, disodium pamoate, and sodium deoxycholate-to enhance compatibility with hydrophobic Poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Complexation efficiencies (CE) reached up to 92.26 %, with ciprofloxacin pamoate (CIP-PAM) achieving over 90 % CE at a 1:0.5 M ratio. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses showed reduced crystallinity across all complexes, with CIP-PAM exhibiting an amorphous form. Optical photothermal infrared spectroscopy (O-PTIR) confirmed uniform complexation within particles, while CIP-PAM displayed a broad peak and weak intensity in the 900-1300 cm region, supporting its amorphous nature. Log P values demonstrated increased hydrophobicity for all complexes, with ciprofloxacin oleate (CIP-OLE) showing a 93-fold increase (p < 0.001). In vitro dissociation patterns varied: CIP-OLE maintained steady release in DW (49.7 %) and PBS (32.3 %) over 48 h, whereas CIP-PAM exhibited strong stability in DW (25.2 %) and a contrasting 68.1 % release in PBS, highlighting solvent-dependent dissociation behaviors. PLGA nanoparticles prepared via S/O/W achieved particle sizes under 200 nm, with CIP-PAM showing the highest encapsulation efficiency (63.02 % vs 17.21 % (CIP)). These findings underscore the importance of counter ion selection to optimize CIP compatibility with hydrophobic carriers, providing a basis for improved drug loading of hydrophilic antibiotics.
本研究通过环丙沙星（CIP）与五种抗衡离子（油酸钠、月桂酸钠、癸酸钠、双羟萘酸二钠和脱氧胆酸钠）进行疏水离子配对，研究其物理化学转变，以增强与疏水性聚（乳酸-乙醇酸共聚物）（PLGA）纳米颗粒的相容性。络合效率（CE）高达92.26%，在1:0.5摩尔比下，环丙沙星双羟萘酸盐（CIP-PAM）的络合效率超过90%。差示扫描量热法（DSC）和X射线衍射（XRD）分析表明，所有络合物的结晶度均降低，CIP-PAM呈现无定形形式。光热红外光谱（O-PTIR）证实颗粒内络合均匀，而CIP-PAM在900-1300cm区域显示出宽峰和弱强度，支持其无定形性质。Log P值表明所有络合物的疏水性均增加，环丙沙星油酸盐（CIP-OLE）增加了93倍（p < 0.001）。体外解离模式各不相同：CIP-OLE在48小时内在去离子水（49.7%）和磷酸盐缓冲液（PBS，32.3%）中保持稳定释放，而CIP-PAM在去离子水（25.2%）中表现出很强的稳定性，在PBS中的释放率为68.1%，形成对比，突出了溶剂依赖性解离行为。通过S/O/W法制备的PLGA纳米颗粒粒径小于200nm，CIP-PAM的包封率最高（63.02%，而CIP为17.21%）。这些发现强调了选择抗衡离子以优化CIP与疏水性载体相容性的重要性，为提高亲水性抗生素的载药量提供了依据。
