Key result
Remotely loaded Lip-DOX-HDZ demonstrated ~4-fold lower toxicity and higher selectivity for normal cells compared to breast cancer cells.
Why the study?
Combining doxorubicin with hydralazine has been proposed as a cardioprotective combination therapy to reduce doxorubicin dosing, prompting investigation of remote co-loading into PEGylated liposomes.
Does co-loading doxorubicin and hydralazine into PEGylated liposomes reduce cytotoxicity in normal cardiac cells while maintaining efficacy against breast cancer cells in vitro?
Does co-loading doxorubicin and hydralazine into PEGylated liposomes reduce cytotoxicity in normal cardiac cells while maintaining efficacy against breast cancer cells in vitro?
Liposomal co-delivery of doxorubicin and hydralazine offers a promising strategy to maintain anti-cancer efficacy while potentially reducing cardiotoxicity.
Supports further liposomal co-loading exploration in vitro; leaves open clinical translation for reduced-dose doxorubicin cardioprotection.
Doxorubicin (DOX), an anthracycline chemotherapeutic agent, demonstrates efficacy against various types of cancer. Combining DOX with the antihypertensive drug hydralazine (HDZ) has been proposed as cardioprotective combination therapy, allowing for the use of a reduced DOX dose. The current study describes the remote co-loading of DOX and HDZ into PEGylated liposomes using, for the first time, a simultaneous pH gradient technique. First, PEGylated liposomes were prepared using an ethanol injection method and remotely loaded with DOX and HDZ. Then, DOX- and HDZ-loaded liposomes (Lip-DOX-HDZ) were characterized using DLS, TEM, FTIR, thermal analysis, drug leakage, and stability. Furthermore, the cellular uptake and cytotoxicity were evaluated in two human breast cancer cell lines (MCF7 and MDA-MB-231) and two normal cell lines (human dermal fibroblasts (HDFs) and rat cardiac cells (H9C2)). The results revealed that Lip-DOX-HDZ had a particle size of 158 ± 18 nm, PDI of 0.22 ± 0.08, and zeta potential of −22 ± 5 mV. The encapsulation efficiency of DOX and HDZ was 90% and 30%, respectively. Moreover, the IC50 values of Lip-DOX-HDZ showed higher cytotoxicity against the MDA-MB-231 (5.5 ± 0.4 µM) and MCF7 (6.25 ± 0.9 µM) breast cancer cell lines compared to normal cells: HDF cells (20 ± 3.0 µM) and H9C2 cardiac cells (19.37 ± 2.0 µM). Our study found that remotely loaded Lip-DOX-HDZ showed a ~4-fold lower toxicity and selectivity for normal cells (HDFs and H9C2), compared to breast cancer cells. This suggests that Lip-DOX-HDZ is a promising nanocarrier for both DOX and HDZ, clinically potent molecules.
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Alshaer et al. (2025) studied Breast cancer. PEGylated liposomes co-loaded with doxorubicin and hydralazine (Lip-DOX-HDZ) vs. Normal cells (HDFs and H9C2) was evaluated on Cytotoxicity (IC50). Remotely loaded Lip-DOX-HDZ demonstrated ~4-fold lower toxicity and higher selectivity for normal cells compared to breast cancer cells.
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