Development of Targeted Nano Drug Delivery System Loaded With Naringenin and Its Derivative for Breast Cancer Cells

Abstract

Development of appropriate drug delivery systems is one of the essential aspects newlinefor successful delivery of drugs with poor aqueous solubility. By using colloidal newlinenanoparticles, we can possibly enhance the efficacy of chemotherapy agents and newlinealso lower their side effects. Polymer nanocarriers have several advantages to their newlinecredit such as synergistic delivery of drugs, limited toxicity and specific interaction newlinewith tumor cells, longer circulation times, and enhanced cellular uptake. In the newlinepresent study, a nanocarrier was synthesized using chitosan and dextran sulfate to newlineencapsulate naringenin and improve its therapeutic potential. Carboxymethyl newlinechitosan was synthesized to improve the water solubility of the polymer. In order newlineto achieve targeted and stimuli sensitive drug delivery, carboxymethyl chitosan newlinewas conjugated with folic acid and naringenin was modified with 2-hydroxy newlinebenzoyl hydrazine. The nanocarriers were characterized to understand them newlinephysically and chemically. They were then studied in breast cancer cell lines to newlineunderstand if they modify any cancer pathways. newlineThe flavanone naringenin (Nar) and a benzoyl hydrazine derivative of naringenin newline(Nar-Bhz) were studied to understand their antagonistic activity against breast newlinecancer proteins using molecular docking study. Nar and Nar-Bhz showed newlinesignificant activity against the proteins Survivin, Estrogen Receptor and#945;, Akt1, and newlineEpidermal Growth Factor Receptor. Chitosan and dextran sulfate were used to newlinesynthesis a nanocarrier for naringenin using the complex coacervation method. The newlinewater soluble derivative of chitosan known as carboxymethyl chitosan was newlinesynthesized and used as starting material for synthesis of nanocarrier for naringenin newline2-hydroxy benzoyl hydrazone. To make the nanocarrier targeted towards cancer newlinecells, carboxymethyl chitosan was conjugated with folic acid. Both the systems had newlinegood loading and encapsulation efficiencies and showed sustained drug release. newlineThey also showed high cytotoxicity against the MCF-7 breast cancer cells. newline