The impact of phospholipids with high transition temperature to enhance Redox-Sensitive liposomal doxorubicin efficacy in colon carcinoma model

In this study, we have developed a redox-sensitive (RS) liposomal doxorubicin formulation by incorporating 10,10'-diselanediylbis decanoic acid (DDA) organoselenium compound as the RS moiety. Hence, several RS liposomal formulations were prepared by using DOPE, HSPC, DDA, mPEG2000-DSPE, and cholesterol. In situ drug loading using a pH gradient and citrate complex yielded high drug to lipid ratio and encapsulation efficiency (100%) for RS liposomes. Liposomal formulations were characterized in terms of size, surface charge and morphology, drug loading, release properties, cell uptake and cytotoxicity, as well as therapeutic efficacy in BALB/c mice bearing C26 tumor cells. The formulations showed an average particle size of 200nm with narrow size distributions (PDI < 0.3), and negative surface charges varying from -6 mV to -18.6mV. Our study confirms that the presence of the DDA compound in liposomes is highly sensitive to hydrogen peroxide at 0.1% w/v, resulting in a significant burst release of up to 40%. The in vivo therapeutic efficacy study in BALB/c mice bearing C26 colon carcinoma confirmed the promising function of RS liposomes in the tumor microenvironment which led to a prolonged median survival time (MST). The addition of hydrogenated soy phosphatidylcholine (HSPC) with a high transition temperature (Tm: 52-53.5°C) extended the MST of our 3-component formulation of F14 (DOPE/HSPC/DDA) to 60 days in comparison to Caelyx (PEGylated liposomal Dox), which is not RS-s...
Source: Chemistry and Physics of Lipids - Category: Lipidology Authors: Source Type: research