Co-Encapsulation of Doxorubicin HCl and Paclitaxel in Nanovesicles for Enhanced Breast Cancer Therapy

Abstract Breast cancer is a prevalent malignancy that can metastasize to distant organs if left untreated, leading to significant morbidity. While chemotherapy is commonly used, it has drawbacks like low tissue availability, short circulation time, and toxicity to healthy cells. The objective of this study was to develop and characterize three different nanovesicles loaded with doxorubicin hydrochloride and paclitaxel, hypothesizing that this combination would enhance tumor targeting, reduce dosing and toxicity, and improve patient compliance. A validated UPLC method was developed for simultaneous detection and quantitation of both drugs, showing linearity over 3.13–50 µg/mL. Retention times were 1.53 and 4.06 min for doxorubicin hydrochloride and paclitaxel, respectively. Using thin-film hydration technique, blank and drug-loaded liposomes, transfersomes, and niosomes were formulated. Nanovesicles were characterized for size (150–250 nm), polydispersity index (0.14–0.20), and zeta potential (-0.56 to + 0.54 mV). Drug loading was 2.0–2.5% for doxorubicin hydrochloride and 7.0–7.5% for paclitaxel, with high encapsulation efficiency. Drug release studies showed sustained release for up to 72 h. Nanovesicles remained stable for at least seven days at room temperature and 4⁰C. Cytotoxicity and apoptosis studies using MTT assay and flow cytometry on MDA-MB 231 breast cancer cells revealed that the drug-loaded nanovesicles exhibited potent cytotoxicity and induced apoptotic cell death more effectively than individual drug solutions. In conclusion, this study successfully developed three nanovesicular systems co-loaded with doxorubicin hydrochloride and paclitaxel, demonstrating their potential as effective drug delivery systems for breast cancer treatment. Graphical Abstract Created in BioRender. Dang, L. (2025) https://BioRender.com/h14t77