Subi Tamil Mani, Selvasudha Nandhakumar, Priyadharshini Sivakumar, Kumar Pradeep, Singh Rakesh, Vasanthi Hannah Rachel
Natural Products Research Laboratory, Department of Biotechnology, Pondicherry University, Puducherry, 605014, India.
Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, 605006, India.
Appl Biochem Biotechnol. 2024 Dec;196(12):8763-8790. doi: 10.1007/s12010-024-04987-3. Epub 2024 Jun 27.
Plumbagin is a naphthoquinone from the roots of the Plumbago species and exhibits anticancer activity. Translational usage of plumbagin in biomedical sciences is restricted due to its poor solubility and bioavailability. Therefore, pH-responsive plumbagin-loaded vaginal nanoformulations with polylactic acid (PLA)-chitosan polymeric coat were fabricated by inotropic gelation technique. Among the four (F1, F2, F3, F4) nanoformulations prepared, F3 exhibited good interaction of polymers with plumbagin as evidenced by FTIR, XRD, and thermal analysis. The positive zeta potential (48.4 ± 5.57 mV), optimal size (694 ± 65.76 nm), low PDI (0.157), and good encapsulation efficiency (77.8 ± 3.62%) of F3 were significant. The indirect method of drug loading (58.35 ± 5.00%) confirmed the drug content of about 495.44 ± 5.00 µg of plumbagin in 1 mg of F3. The drug loading pattern was confirmed by TEM analysis, and the spherical morphology of the nanocomposite was confirmed by SEM analysis. F3 formulation showed 46% and 25.2% of drug release in 24 h in simulated vaginal fluid at pH 4.5 and 7 respectively with sustained release and hydrolyses of lactic acid from PLA. Among all the nanoformulations evaluated, nanoformulation F3 with promising physicochemical properties showed good antifungal and antibacterial activity against various fungal and bacterial strains. F3 exhibited potent cytotoxicity with an IC50 of 3.6 ± 0.12 µg/ml for HeLa and an IC50 of 0.81 ± 0.01 µg/ml for SiHa cells. Altogether, the nanoformulation F3 exhibited potent antimicrobial activity against vaginal infections and cytotoxicity against cervical cancer cell lines.
白花丹醌是一种从白花丹属植物根部提取的萘醌，具有抗癌活性。由于其溶解性和生物利用度较差，白花丹醌在生物医学领域的转化应用受到限制。因此，采用离子凝胶技术制备了具有聚乳酸（PLA）-壳聚糖聚合物涂层的pH响应性载白花丹醌阴道纳米制剂。在所制备的四种纳米制剂（F1、F2、F3、F4）中，F3通过傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）和热分析证明聚合物与白花丹醌具有良好的相互作用。F3的正zeta电位（48.4±5.57 mV）、最佳粒径（694±65.76 nm）、低多分散指数（PDI，0.157）和良好的包封率（77.8±3.62%）具有显著意义。间接载药法（58.35±5.00%）证实1 mg F3中白花丹醌的药物含量约为495.44±5.00 μg。通过透射电子显微镜（TEM）分析确认了载药模式，通过扫描电子显微镜（SEM）分析确认了纳米复合材料的球形形态。F3制剂在pH 4.5和7的模拟阴道液中24小时分别释放46%和25.2%的药物，具有缓释作用且聚乳酸发生乳酸水解。在所有评估的纳米制剂中，具有良好理化性质的纳米制剂F3对各种真菌和细菌菌株表现出良好的抗真菌和抗菌活性。F3对HeLa细胞表现出强大的细胞毒性，IC50为3.6±0.12 μg/ml，对SiHa细胞的IC50为0.81±0.04 μg/ml。总之，纳米制剂F3对阴道感染表现出强大的抗菌活性，对宫颈癌细胞系表现出细胞毒性。
