Synthesis, characterization, and evaluation of in vitro cytotoxicity and in vivo antitumor activity of asiatic acid-loaded poly lactic-co-glycolic acid nanoparticles: A strategy of treating breast cancer

被引:10
作者
Dutta, Sayanta [1 ]
Chakraborty, Pratik [2 ]
Basak, Susmita [2 ]
Ghosh, Sumit [1 ]
Ghosh, Noyel [1 ]
Chatterjee, Sharmistha [1 ]
Dewanjee, Saikat [2 ]
Sil, Parames C. [1 ]
机构
[1] Bose Inst, Div Mol Med, P-1-12,CIT Scheme 7M, Kolkata 700054, India
[2] Jadavpur Univ, Dept Pharmaceut Technol, Adv Pharmacognosy Res Lab, Kolkata 700032, India
关键词
Apoptosis; Asiatic acid; Breast cancer; Cytotoxicity; Polymeric nanoparticles; POLYMERIC NANOPARTICLES; HEPATOCELLULAR-CARCINOMA; DRUG-DELIVERY; ACTIVATION; STRESS; CELLS; INHIBITION; PACLITAXEL; APOPTOSIS; MEMBRANE;
D O I
10.1016/j.lfs.2022.120876
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Asiatic acid (AA), an aglycone of pentacyclic triterpene glycoside, obtained from the leaves of Centella asiatica exerts anticancer effects by inhibiting cellular proliferation and inducing apoptosis in a wide range of carcino-genic distresses. However, its chemotherapeutic efficacy is dampened by its low bioavailability. Polymeric nanoparticles (NPs) exhibit therapeutic efficacy and compliance by improving tissue penetration and lowering toxicity. Thus, to increase the therapeutic effectiveness of AA in the treatment of breast cancer, AA-loaded poly lactic-co-glycolic acid (PLGA) NPs (AA-PLGA NPs) have been formulated. The AA-PLGA NPs were characterized on the basis of their average particle size, zeta potential, electron microscopic imaging, drug loading, and entrapment efficiency. The NPs exhibited sustained drug release profile in vitro. Developed NPs exerted dose -dependent cytotoxicity to MCF-7 and MDA-MB-231 cells without damaging normal cells. The pro-oxidant and pro-apoptotic properties of AA-PLGA NPs were determined by the study of the cellular levels of SOD, CAT, GSH-GSSG, MDA, protein carbonylation, ROS, mitochondrial membrane potential, and FACS analyses on MCF-7 cells. Immunoblotting showed that AA-PLGA NPs elicited an intrinsic pathway of apoptosis in MCF-7 cells. In vivo studies on female BALB/c mice exhibited reduced volume of mammary pad tumor tissues and augmented expression of caspase-3 when administered with AA-PLGA NPs. No systemic adverse effect of AA-PLGA NPs was observed in our studies. Thus, AA-PLGA NPs can act as an efficient drug delivery system against breast cancer.
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页数:13
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