A Novel Strategy for Treating Squamous Cell Carcinoma of the Head and Neck with Nano encapsulated Drugs Based on Thermosensitive Delivery System

Abstract

Current therapeutics for treatment of head and neck squamous cell carcinoma (HNSCC) are plagued by severe side effects. Local drug delivery for HNSCC has emerged as a more effective and safe treatment strategy. Lauric acid (LA) is saturated fatty acid that demonstrated many beneficial therapeutic features. This study aimed to explore a novel use of LA as injectable thermosensitive drug carrier for anticancer drugs for treatment of HNSCC. LA was characterized in terms of melting temperature and gelation time. Micellar formulations Styrene Maleic Acid (SMA) of gefitinib (G), cisplatin (CDDP) and doxorubicin (DOXO) were synthesized and characterized. We further tested the anticancer efficacy of the different formulations in LA in vitro in HNSCC cell line as well as in vivo in mice model of HNSCC. LA used in this study was modified to achieve a melting temperature of 38.7° C and a gelation temperature at 37.7° C within 40 seconds. All the micellar formulations had negative charge with the molecular size of 155 ± 77 nm for G-SMA micelles, CDDP-SMA size was 174.2 ± 87 nm, and DOXO-SMA size was 127.2 ± 89 nm. Drug-loaded LA systems showed slow release with maximum release of 32% at 3 days. LA demonstrated in vivo biocompatibility and biodegradability after 1 month follow up. The addition of LA to both free and micellar drugs in vitro enhanced its cytotoxic effect except for G. LA delivery system improved the safety of chemotherapeutics used in the study, when injected in mice model of HNSCC. LA loaded with chemotherapeutics formulations abolished tumor progression and further reduced the original tumor volume significantly over one month of treatment compared to almost 4-fold increase in tumor volume in untreated control groups. This study proves the value of LA delivery system for local delivery of chemotherapeutics and offers safe, simple, and effective strategy for the delivery of clinically relevant anticancer hydrophobic drugs.