Salave Sagar, Shinde Suchita Dattatray, Rana Dhwani, Sahu Bichismita, Kumar Hemant, Patel Rikin, Benival Derajram, Kommineni Nagavendra
National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad 382355, India.
Intas Pharmaceuticals Ltd., Matoda Village, Ahmedabad 382210, India.
Pharmaceutics. 2023 Feb 11;15(2):608. doi: 10.3390/pharmaceutics15020608.
Bone-specific functionalization strategies on liposomes are promising approaches to delivering the drug in osteoporotic conditions. This approach delivers the drug to the bone surface specifically, reduces the dose and off-target effects of the drug, and thereby reduces the toxicity of the drug. The purpose of the current research work was to fabricate the bone-specific peptide conjugated pegylated nanoliposomes to deliver anabolic drug and its physicochemical evaluations. For this, a bone-specific peptide (SDSSD) was synthesized, and the synthesized peptide was conjugated with a linker (DSPE-PEG2000-COOH) to obtain a bone-specific conjugate (SDSSD-DSPE). Purified SDSSD-DSPE was characterized by HPLC, Maldi-TOF, NMR, and Scanning Electron Microscope/Energy Dispersive Spectroscopy (SEM/EDS). Further, peptide-conjugated and anabolic drug-encapsulated liposomes (SDSSD-LPs) were developed using the ethanol injection method and optimized by Central Composite Design (CCD) using a statistical approach. Optimized SDSSD-LPs were evaluated for their physicochemical properties, including surface morphology, particle size, zeta potential, in vitro drug release, and bone mineral binding potential. The obtained results from these studies demonstrated that SDSSD-DSPE conjugate and SDSSD-LPs were optimized successfully. The particle size, % EE, and zeta potential of SDSSD-LPs were observed to be 183.07 ± 0.85 nm, 66.72 ± 4.22%, and -25.03 ± 0.21 mV, respectively. SDSSD-LPs demonstrated a sustained drug release profile. Further, the in vitro bone mineral binding assay demonstrated that SDSSD-LPs deliver the drug to the bone surface specifically. These results suggested that SDSSD-LPs could be a potential targeting approach to deliver the anabolic drug in osteoporotic conditions.
脂质体上的骨特异性功能化策略是在骨质疏松症情况下递送药物的有前景的方法。这种方法将药物特异性地递送至骨表面，减少药物剂量和脱靶效应，从而降低药物毒性。当前研究工作的目的是制备骨特异性肽偶联的聚乙二醇化纳米脂质体以递送合成代谢药物并对其进行物理化学评估。为此，合成了一种骨特异性肽（SDSSD），并将合成的肽与连接子（DSPE-PEG2000-COOH）偶联以获得骨特异性偶联物（SDSSD-DSPE）。纯化后的SDSSD-DSPE通过高效液相色谱、基质辅助激光解吸电离飞行时间质谱、核磁共振以及扫描电子显微镜/能量色散光谱（SEM/EDS）进行表征。此外，采用乙醇注入法制备了肽偶联且包封有合成代谢药物的脂质体（SDSSD-LPs），并使用统计方法通过中心复合设计（CCD）进行优化。对优化后的SDSSD-LPs进行了物理化学性质评估，包括表面形态、粒径、zeta电位、体外药物释放以及骨矿物质结合潜力。这些研究获得的结果表明，SDSSD-DSPE偶联物和SDSSD-LPs已成功优化。观察到SDSSD-LPs的粒径、包封率和zeta电位分别为183.07±0.85 nm、66.72±4.22%和-25.03±0.21 mV。SDSSD-LPs表现出持续的药物释放曲线。此外，体外骨矿物质结合试验表明，SDSSD-LPs可将药物特异性地递送至骨表面。这些结果表明，SDSSD-LPs可能是在骨质疏松症情况下递送合成代谢药物的一种潜在靶向方法。
