A facile approach for fabricating CD44-targeted delivery of hyaluronic acid-functionalized PCL nanoparticles in urethane
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ORIGINAL ARTICLE
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 1 & Chandra Bhushan Tripathi 1 & Malti Arya 1 & Jovita Kanoujia 1 & Mahendra Singh 1 & Abhishek Yadav 1 & Shubhini A. Saraf 1
# Controlled Release Society 2018
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 CAPloaded 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. HAPCL-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. Keywords NSCLC . Layer by layer technique . PCL . ROS . Apoptosis
Introduction Lung cancer (LC) is one of the most common cancers occurring worldwide, accounting for 20% of total cancer mortality [1, 2]. Broadly LC is divided into two major types, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), of which NSCLC occurrence accounts for 85% of LC patients [3]. The Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13346-018-0575-8) contains supplementary material, which is available to authorized users. * Shubhini A. Saraf [email protected] 1
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow, U.P. 226025, India
absence of early diagnosis, poor prognosis, and development of resistance to chemotherapeutic agents and an overall less than 5-year survival rate are the prime hindrances for effective LC treatment [
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