Abstract
Lung carcinoma is the most common cancer in men and second in women (preceded by breast cancer) worldwide. Around 1 in 10 of all cancers diagnosed in men, lung cancer contributed to a total fraction of 20% cancer deaths. Naringenin (NAR) is well known for its chemopreventive properties since ancient times but lacks an appropriate delivery carrier. The objective of present study was to expand the functionality of naringenin loaded poly caprolactone (PCL) nanoparticles in terms of release, chemoprevention and therapeutics. Polymeric nanoparticles such as PCL lack target specificity; hence, surface modification was attempted using layer by layer technique (LBL) to achieve improved and desired delivery as well as target specificity. The designing of Hyaluronic acid (HA) decorated PCL nanoparticles were prepared by utilizing self-assembling LBL technique, where a polycationic layer of a polymer was used as a linker for modification between two polyanionic layers. Additionally, an attempt has been made to strengthen the therapeutic efficacy of PCL nanocarriers by active targeting and overcoming the extracellular matrix associated barriers of tumors using HA targeting cluster determinant 44 receptor (CD44). Cell cytotoxicity study on A549 cells and J774 macrophage cells depicted enhanced anticancer effect of NAR-HA@CH-PCL-NP with safe profile on macrophages. Uptake study on A549 cells advocated enhanced drug uptake by cancer cells. Cell cycle arrest analysis (A549 cell lines) demonstrated the superior cytotoxic effect and active targeting of NAR-HA@CH-PCL-NP. Further chemopreventive treatment with NAR-HA@CH-PCL-NP was found effective in tumor growth inhibitory effect against urethane-induced lung cancer in rat. In conclusion, developed formulation possesses a promising potential as a therapeutic and chemopreventive agent against urethane-induced lung carcinoma in albino wistar rats.
Highlights
Lung cancer (LC) is the most frequent cancer occurring globally reported in both men and women [1]
LC is divided into two major types, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), of which NSCLC alone accounts for 85% [3,4]
Present investigation promises the designing of Hyaluronic acid (HA) decorated layer by layer assembled poly caprolactone (PCL) NPs sandwiched with CH for oral delivery to attenuate lung cancer
Summary
Lung cancer (LC) is the most frequent cancer occurring globally reported in both men and women [1]. Most opted treatment strategies include radiotherapy and chemotherapy which pose challenges to effective treatment of LC [6] These conventional treatments have discouraging outcomes due to limitations, namely dose-dependent toxicity, low selectivity, resistance development and compromised delivery of chemotherapeutic agents to lung tissue due to high tumor interstitial pressure [7]. A wide variety of polymeric nanoparticles (NPs) have been reported which can be surface engineered so as to protect the agent from reticuloendothelial system RES uptake during its circulation in the blood stream and may serve the dual purpose of targeting cancer cells while protecting normal non-targeted tissues from toxicity [3,8] Previous investigations proved these surface modified NPs to be biocompatible, having better cellular uptake and ability to target tumor tissue [9]. When a surface modified NP approaches these overexpressed receptors, they rapidly internalize it and the drug is directly delivered to these cells [1]
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