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Surface-engineered nanostructured lipid carrier systems for synergistic combination oncotherapy of non-small cell lung cancer

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Abstract

Nanoparticle-aided combination chemotherapy offers several advantages like ratiometric drug delivery, dose reduction, multi-targeted therapy, synergism, and overcoming multi-drug resistance. The current research was instigated to facilitate targeted and ratiometric co-delivery of docetaxel (DT) and curcumin (CR) through the development of folate (FA)–appended nanostructured lipid carriers (NLCs), i.e., FA-DTCR-NLCs to lung cancer cells. The FA-DTCR-NLCs were formulated by employing a scaleable and solvent-free high-pressure homogenization approach. The FA-DTCR-NLCs were evaluated for in vitro and in vivo characteristics using suitable analytical and statistical techniques. The FA-DTCR-NLCs demonstrated physicochemical properties and particokinetics suitable for targeted, ratiometric co-delivery of the anticancer agents. This was further affirmed by significantly better in vivo relative bioavailability of DT (24.85 fold) with FA-DTCR-NLCs as compared with Taxotere® (p < 0.05) and cell line studies. A significant tumor regression was observed from the results of tumor staging in a murine model of lung carcinoma (p < 0.05). Immunostaining of the tumor sections with tumor differentiation biomarkers suggested considerably higher apoptotic, anti-proliferative, anti-angiogenic, and anti-metastatic potential of FA-DTCR-NLCs compared with Taxotere®. In vivo toxicity assessment of the FA-DTCR-NLCs demonstrated a noteworthy reduction in DT associated side effects. The in vitro and in vivo pre-clinical findings prove the therapeutic and safety pre-eminence of FA-DTCR-NLCs for the treatment of NSCLC.

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Acknowledgments

The authors are thankful to the Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India, for providing the necessary facilities to generate the manuscript that is a part of a Doctor of Philosophy (Ph.D.) research work of Ms. Shruti U. Rawal to be submitted to Nirma University, Ahmedabad, India.

Funding

The authors were financially assisted by Nirma University, Ahmedabad, India, in form of Major Research Project (NU/Ph.D./Major Res Pro/IP/16-17/669) which also provided necessary facilities to carry out the research work. This study was funded by the Department of Science and Technology (DST) Fund for Improvement of S&T Infrastructure (FIST) (Grant No. SR/FST/LSI-607/2014), Government of India, for the establishment of equipment facility. Ms. Shruti Rawal was supported by Nirma University which provided the Junior Research Fellowship and Senior Research Fellowship.

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  1. Department of Pharmaceutics, Institute of Pharmacy, Nirma University, SG Highway Ahmedabad 382481, Gujarat, Chharodi, India

    Shruti Rawal & Mayur Patel

  2. Department of Pharmacology, Institute of Pharmacy, Nirma University, SG Highway Ahmedabad 382481, Gujarat, Chharodi, India

    Vivek Bora & Bhoomika Patel

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Rawal, S., Bora, V., Patel, B. et al. Surface-engineered nanostructured lipid carrier systems for synergistic combination oncotherapy of non-small cell lung cancer. Drug Deliv. and Transl. Res. 11, 2030–2051 (2021). https://doi.org/10.1007/s13346-020-00866-6

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