Doxorubicin and Crocin Co-delivery by Polymeric Nanoparticles for Enhanced Anticancer Potential In Vitro and In Vivo

Abstract

Development of a biodegradable nanoplatform poly-(lactic-co-glycolic acid) (PLGA) for co-delivery of two drugs is hugely imperative and beneficial in anticancer therapeutics. In this study, co-delivery of a natural phytoconstituent, crocin (carotenoid), and a commonly prescribed drug, doxorubicin, was attempted using a nanoparticulate platform in the form of PLGA nanoparticles. Doxorubicin was chemically conjugated, while crocin was encapsulated physically in prepared PLGA nanoparticles (PDCR NPs). Prepared NPs were well-characterized for size, ζ, and surface morphology. PDCR NPs were of 174.2 ± 1.57 nm in size. The transmission electron microscopy (TEM) and atomic force microscopy (AFM) images revealed the spherical shape and smooth surface morphology of the nanoparticles, respectively. The entrapment efficiency and drug loading were found to be 58.95 ± 2.58 and 13.89 ± 1.09%, respectively. The drug release pattern of PDCR NPs showed a sustained and controlled release pattern throughout 48 h in PBS buffer pH 7.4 and acetate buffer pH 6.5. PDCR NPs were significantly less hemolytic than doxorubicin (p < 0.0001). Investigational formulation selectively produced cytotoxic effects on breast cancer cells via decreasing reactive oxygen species (ROS) and altering the mitochondrial potential that led to apoptosis with cell-cycle arrest at the G2/M phase. Prepared NPs were able to upregulate the caspase levels as well as efficient uptake by cells in a time-dependent manner. In vivo plasma drug profile studies in healthy rats revealed prolonged persistence of crocin and doxorubicin in systemic circulation. Additionally, the PDCR NPs portrayed reduced tumor volume as compared to control groups in the tumorinduced animal studies, which were favorable. Conclusively, the co-delivery of natural anticancer bioactive crocin along with doxorubicin in PDCR NPs provides a possible controlled-release nanoplatform for efficient drug delivery in vitro and in vivo.

Biodegradable nanoparticulate co-delivery of flavonoid and doxorubicin: Mechanistic exploration and evaluation of anticancer effect in vitro and in vivo

“…The formulation was found to possess better antiproliferative potential in comparison to individual counterparts D1 (See Ref. [45] ), D2 (MDA-MB-231: 2.98 ± 0.98 µM; T47D: 4.17 ± 0.97 µM and MCF-7: 4.75 ± 0.88 µM) and PND1 (MDA-MB-231: 2.87 ± 0.67 µM; T47D: 3.87 ± 0.53 µM and MCF-7: 3.98 ± 0.29 µM) as graphically summarised in Fig. 4A .…”

Elucidating shape-mediated drug carrier mechanics of hematite nanomaterials for breast cancer therapeutics

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Fisetin-Loaded Nanostructured Lipid Carriers: Formulation and Evaluations against Advanced and Metastatic Melanoma

“…Cell apoptosis analysis was performed by suspending the cells in Annexin binding buffer and incubating them with Annexin-V and PI for 30 min at room temperature. Both analyses were performed by flow cytometry (BD FACSVerse) using appropriate compensation and threshold settings …”

“…Both analyses were performed by flow cytometry (BD FACSVerse) using appropriate compensation and threshold settings. 39 2.6.5. Evaluation of the Expression of Apoptotic and Antioxidant Genes.…”