Efficiency of Azithromycin-Loaded Lipid Polymer Hybrid Nano-vehicle as a Repurposing formulation in Colon Cancer Management

Abstract

Colorectal cancer (CRC) despite notable progress in treatment still ranks third in terms of occurrences and second in terms of mortality. Numerous synthetic chemotherapies have been used in CRC; nevertheless, they do not specifically target cancerous cells resulting in serious side effects and significant harm to healthy cells. Accordingly, many alternative safer therapies have been extensively investigated against CRC. Azithromycin (AZI), a member of macrolides antibiotics, has been reported to inhibit the proliferation of cancer cells by targeting mitochondria and eradicating cancer cells. Despite its promising therapeutic activity, it is restricted by its poor aqueous solubility leading to efforts focusing on the development of safe and efficient anticancer Nano carriers. Liposomes are the most widely studied Nano-drug carriers in drug delivery. Compared with other Nano carriers, liposomes exhibit prominent properties that include targeted delivery, high biocompatibility, biodegradability, low toxicity, and improved therapeutic indices. Thus, the current work aims is to design a liposome to augment azithromycin anticancer effects. Liposome was prepared from soybean phospholipid using an ethanol injection technique and coated chitosan. The designed coated and uncoated systems were characterized both physicochemically and on colorectal cancer cell line in vitro. The results displayed Nano metric size range for azithromycin-loaded uncoated and coated liposomes of values 65.5± 2.83 nm and 73.53 ± 2.01 nm, respectively with uni-modal particle size distribution with PDI less than 0.3. The shifting of the negative charge (-17.22± 5.99 mV) of the uncoated liposomes to the positive charge (13.17± 3.34 mV) of the coated one approved the success of the coating. The formulation showed ideal characteristics of 70% AZI entrapment and in vitro controlled release. It displayed a safe profile on HT29 cell line, with the coated formulation having the lowest IC50= 24.17 μM at 24 hours that even decreases at longer time intervals, which confirms its potential for colorectal cancer management.