Swami Rajan, Kumar Yogesh, Chaudhari Dasharath, Katiyar Sameer S, Kuche Kaushik, Katare Parmeshwar B, Banerjee Sanjay K, Jain Sanyog
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali), Punjab, India.
Drug Discovery Research Centre, Translational Health Science and Technology Institute, Faridabad 121001, India.
Mater Sci Eng C Mater Biol Appl. 2021 Jan;120:111664. doi: 10.1016/j.msec.2020.111664. Epub 2020 Oct 22.
Combining the bio-therapeutics with chemotherapeutic drugs can assist in augmenting the therapeutic standards by increasing the efficacy and decreasing the toxicity. Hence, in the present investigation Docetaxel (DTX) loaded pH-sensitive SIRT1 shRNA complexed lipoplex (DTX-lipoplex) were developed and explored for their improved breast cancer potential. The DTX-lipoplex were prepared by solvent evaporation and rehydration method and were evaluated for various quality attributes (particle size, % entrapment efficiency, hemotoxicity, DNA stability efficiency etc.), in vitro drug release, cell culture assays, antitumor efficacy and in vivo toxicity. The DTX-lipoplex exhibited a size of 200 nm and zeta-potential of ~20 mV with ~70% encapsulation. Through systematic in vitro and in vivo examinations, DTX-lipoplex showed ~3 fold higher DTX titre within the tumor cells thereby significantly reducing the tumor burden (78%) when compared to the marketed non pH sensitive lipid transfection agent and clinical counterpart i.e. Taxotere®. Thus, to conclude it can be said that co-delivering DTX and SIRT1 shRNA in a single tumor-specific nano-platform can improve the therapeutic potential of current therapy.
将生物治疗药物与化疗药物相结合，可以通过提高疗效和降低毒性来辅助提高治疗标准。因此，在本研究中，开发了负载多西他赛（DTX）的pH敏感型SIRT1 shRNA复合脂质体（DTX-脂质体），并探索其在改善乳腺癌治疗方面的潜力。DTX-脂质体通过溶剂蒸发和复水法制备，并对其各种质量属性（粒径、包封率、血液毒性、DNA稳定性效率等）、体外药物释放、细胞培养试验、抗肿瘤疗效和体内毒性进行了评估。DTX-脂质体的粒径约为200 nm，zeta电位约为20 mV，包封率约为70%。通过系统的体外和体内研究，与市售的非pH敏感脂质转染剂和临床对照药泰索帝®相比，DTX-脂质体在肿瘤细胞内的DTX效价高出约3倍，从而显著降低肿瘤负荷（约78%）。因此，可以得出结论，在单一肿瘤特异性纳米平台上共同递送DTX和SIRT1 shRNA可以提高当前治疗的治疗潜力。
