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    Oleanolic acid-conjugated human serum albumin nanoparticles encapsulating doxorubicin as synergistic combination chemotherapy in oropharyngeal carcinoma and melanoma

    Year: 2022

    Journal: Int. J. Pharm., Volume 614, FEB 25

    Authors: Kumbham, Soniya; Paul, Milan; Itoo, Asif; Ghosh, Balaram; Biswas, Swati

    Organizations: Center for Human Diseases by BITS-Pilani, India [210088OOC3]; Indian Council of Medical Research (ICMR); DST FIST [SR/FST/LS-II/2018/210]

    Keywords: Combination; Nanoparticles; Cancer; Human serum albumin; Oleanolic acid; Doxorubicin

    Combination chemotherapy produces a superior therapeutic response than monotherapy in cancer. Human serum albumin and a naturally occurring cancer prophylactic/anticancer triterpenoid, oleanolic acid, were conjugated to form self-assembled nanoparticles that entrapped doxorubicin. Dox@HSA-OA NPs were physicochemically characterized for particle size, zeta potential, drug loading, entrapment efficiency, stability, release, and hemocompatibility. The Dox@HSA-OA NPs (particle size. ~ 140 nm) showed commendable loading (14.6 %), entrapment (59.01%) of Dox. The in vitro cell uptake study using human oral squamous carcinoma (FaDuHTB-43) and murine melanoma (B16F10) cells indicated a higher cellular association of Dox@HSA-OA NPs than free Dox. The lowest IC50 of Dox@HSA-OA NPs than Dox against both the cell lines at various time points proved the Dox/HSA-OA-mediated combination chemotherapeutic effect. Dox@HSA-OA NPs demonstrated higher apoptosis and cell cycle arrest (G2/M phase). The Dox@HSA-OA NPs-mediated Dox penetration, cell death/shrinkage were significant in FaDu-HTB-43 spheroids. Dox@HSA-OA NPs showed a better pharmacokinetic profile with increased t(1/2) and Cmax than Dox. The in vivo experiment using B16F10 tumor-bearing mice showed tumor regression, DNA damage, oxidative stress, and apoptosis-induction via the intrinsic pathway to a greater extent following Dox@HSA-OA NPs treatment than Dox. Therefore, the Dox@HSA-OA NPs-mediated combination therapy could be a powerful treatment strategy for solid tumors.
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