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Drug Delivery and Translational Research

, Volume 9, Issue 1, pp 37–52 | Cite as

A facile approach for fabricating CD44-targeted delivery of hyaluronic acid-functionalized PCL nanoparticles in urethane-induced lung cancer: Bcl-2, MMP-9, caspase-9, and BAX as potential markers

  • Poonam Parashar
  • Chandra Bhushan Tripathi
  • Malti Arya
  • Jovita Kanoujia
  • Mahendra Singh
  • Abhishek Yadav
  • Shubhini A. SarafEmail author
Original Article
  • 80 Downloads

Abstract

Lung carcinoma ranks highest in cancer-related death (about 20% of total cancer deaths) due to poor prognosis and lack of efficient management therapy. Owing to the lack of effective therapeutic approaches, survival rate of less than 5 years persists over the years among non-small cell lung cancer (NSCLC) patients. Capsaicin (CAP) is well reported for its antiproliferative and antioxidant properties in various literature but lacks an appropriate delivery carrier. The present study was aimed to develop CAP-loaded hyaluronic acid (HA) nanoparticles (NPs) utilizing layer by layer technique to achieve enhanced and precise delivery as well as target specificity. The NPs were evaluated for in vitro release, particle size, zeta potential, and cytotoxicity on A549 cells. The optimized NPs exhibited a particle size of 194 ± 2.90 nm, − 27.87 ± 3.21 mV zeta potential, and 80.70 ± 4.29% release, respectively, over a period of 48 h. Flow cytometric analysis revealed superior performance of HA-PCL-CAP in terms of suppressed cell viability in A549 cell lines when compared with CAP and PCL-CAP. Further, HA-anchored NPs were evaluated in vivo for their therapeutic efficacy in urethane-induced lung carcinoma in rat model. The superlative therapeutic potential of HA-PCL-CAP was advocated from the results of reactive oxygen species and mitochondrial membrane-mediated apoptosis. HA-PCL-CAP-administered groups presented greater therapeutic efficacy as revealed through reduced tumor volume and improved animal survival rate. A greater drug accumulation in tumor tissue as revealed from biodistribution studies evidences targeting potential of HA-PCL-CAP in urethane-induced lung carcinoma.

Graphical abstract

Keywords

NSCLC Layer by layer technique PCL ROS Apoptosis 

Notes

Acknowledgments

The authors (PP, MA, JK) wish to acknowledge the scholarship received from University Grant Commission during this study.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of concern with respect to the authorship and/or publication of this research article.

Supplementary material

13346_2018_575_MOESM1_ESM.docx (22 kb)
ESM 1 (DOCX 21 kb)

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Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesBabasaheb Bhimrao Ambedkar University (A Central University)LucknowIndia

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