1. Academic Validation
  2. Surface-engineered nanostructured lipid carrier systems for synergistic combination oncotherapy of non-small cell lung cancer

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

  • Drug Deliv Transl Res. 2021 Oct;11(5):2030-2051. doi: 10.1007/s13346-020-00866-6.
Shruti Rawal 1 Vivek Bora 2 Bhoomika Patel 2 Mayur Patel 3
Affiliations

Affiliations

  • 1 Department of Pharmaceutics, Institute of Pharmacy, Nirma University, SG Highway Ahmedabad 382481, Gujarat, Chharodi, India.
  • 2 Department of Pharmacology, Institute of Pharmacy, Nirma University, SG Highway Ahmedabad 382481, Gujarat, Chharodi, India.
  • 3 Department of Pharmaceutics, Institute of Pharmacy, Nirma University, SG Highway Ahmedabad 382481, Gujarat, Chharodi, India. drmayurmpatel@gmail.com.
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.

Keywords

Cell uptake; Folate receptor; NSCLC; Pharmacokinetics; Synergistic combination; Tumor regression.

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