Advanced Drug Delivery Group, School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales 2006, Australia.
The University of Sydney, Sydney Nano Institute, Faculty of Medicine and Health, Sydney Pharmacy School, Sydney, New South Wales 2006, Australia.
Anal Chem. 2020 Jul 21;92(14):9922-9931. doi: 10.1021/acs.analchem.0c01465. Epub 2020 Jul 2.
Use of liposomes encapsulating drug nanocrystals for the treatment of diseases like cancer and pulmonary infections is gaining attention. The potential therapeutic benefit of these engineered formulations relies on maintaining the physical integrity of the liposomes and the stability of the encapsulated drug. With the significant advancement in the microscopic and analytical techniques, analysis of the size and size distribution of these nanosized vesicles is possible. However, due to the limited spatial resolution of conventional vibrational spectroscopy techniques, the chemical composition of individual nanosized liposome cannot be resolved. To address this limitation, we applied atomic force microscopy infrared spectroscopy (AFM-IR) to assess the chemical composition of individual liposomes encapsulating ciprofloxacin in dissolved and nanocrystalline form. Spatially resolved AFM-IR spectra acquired from individual liposomes confirmed the presence of peaks related to N-H bending vibration, C-N stretching and symmetric, and asymmetric vibration of the carboxyl group present in the ciprofloxacin. Our results further demonstrated the effectiveness of AFM-IR in differentiating the liposome containing ciprofloxacin in dissolved or nanocrystalline form. Spectra acquired from dissolved ciprofloxacin had peaks related to the ionised carboxyl group, i.e., at 1576 and 1392 cm, which were either absent or far weaker in intensity in the spectra of liposomal sample containing ciprofloxacin nanocrystals. These findings are highly significant for pharmaceutical scientists to ascertain the stability and physicochemical composition of individual liposomes and will facilitate the design and development of liposomes with greater therapeutic benefits.
脂质体纳米晶药物用于治疗癌症和肺部感染等疾病的方法受到关注。这些工程制剂的潜在治疗益处依赖于保持脂质体的物理完整性和包封药物的稳定性。随着微观和分析技术的显著进步，这些纳米尺寸囊泡的大小和尺寸分布的分析成为可能。然而，由于传统振动光谱技术的空间分辨率有限，无法解析单个纳米脂质体的化学组成。为了解决这一限制，我们应用原子力显微镜红外光谱（AFM-IR）来评估溶解态和纳米晶态环丙沙星包封的单个脂质体的化学组成。从单个脂质体获得的空间分辨 AFM-IR 光谱证实了存在与 N-H 弯曲振动、C-N 伸缩和对称、不对称振动相关的峰，这些峰存在于环丙沙星中。我们的结果进一步证明了 AFM-IR 在区分含有溶解态或纳米晶态环丙沙星的脂质体方面的有效性。溶解态环丙沙星的光谱具有与离子化羧基相关的峰，即在 1576 和 1392 cm 处，而在含有环丙沙星纳米晶的脂质体样品的光谱中，这些峰要么不存在，要么强度要弱得多。这些发现对制药科学家来说非常重要，可以确定单个脂质体的稳定性和物理化学组成，并促进具有更大治疗益处的脂质体的设计和开发。
