1. Academic Validation
  2. Surface-modified nanoparticles of docetaxel for chemotherapy of lung cancer: an intravenous to oral switch

Surface-modified nanoparticles of docetaxel for chemotherapy of lung cancer: an intravenous to oral switch

  • Int J Pharm. 2023 Mar 13;122846. doi: 10.1016/j.ijpharm.2023.122846.
Shruti Rawal 1 Shubham Khot 1 Bora Vivek 1 Bhoomika Patel 1 Mayur M Patel 2
Affiliations

Affiliations

  • 1 Institute of Pharmacy, Nirma University, SG Highway, Chharodi, Ahmedabad: 382 481, Gujarat, India.
  • 2 Institute of Pharmacy, Nirma University, SG Highway, Chharodi, Ahmedabad: 382 481, Gujarat, India. Electronic address: [email protected].
Abstract

Despite being potent, the marketed formulations of Docetaxel (DX) are associated with numerous side effects and are meant for intravenous administration. Advanced pharmaceutical nanotechnology has a significant potential to facilitate the 'intravenous (i.v) to oral switch'. The present research work deals with the development of an orally administrable, folate-receptor-targeted Nanostructured lipid carriers (NLCs) of DX (FA-DX-NLCs) for facilitating oral chemotherapy of lung Cancer while overcoming the bioavailability and toxicity issues. The nanoformulation prepared to employ high-pressure homogenization and lyophilization, was evaluated and statistically analyzed for various in-vitro and in-vivo formulation characteristics. The lyophilized nanoparticles were observed to be spherical with a particle size of 183.4 ± 2.13 (D90), PDI of 0.358 ± 0.03, % EE of 82.41 ± 2.44, % DL of 4.41± 0.54 and a zeta potential of -3.3 ± 0.7 mv. The increased oral in-vivo bioavailability of DX was evident from the plasma-concentration area under the time curve (AUC0-t), which was ∼27-fold greater for FA-DX-NLCs as compared to DX suspension. The orally administered FA-DX-NLCs exhibited excellent antitumor efficacy in a pre-clinical model of lung carcinoma. Tumor staging, histopathology, and immunostaining of the tumors suggested greater anti-proliferative, apoptotic, anti-metastatic, and anti-angiogenic potential as compared to DX-suspension. The pre-clinical toxicity studies affirmed the excellent safety and bio-compatibility of FA-DX-NLCs. The research work presents immense translational potential for switching the DX-based chemotherapy for lung Cancer from 'hospital to home.'

Keywords

Folate receptor; Immunostaining; Lipid nanoparticles; Lymphatic delivery; NSCLC.

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