Doxorubicin and Crocin Co-delivery by Polymeric Nanoparticles for Enhanced Anticancer Potential In Vitro and In Vivo .
Iliyas KhanGaurav JoshiBibekananda SarkarKartik T Nakhatenull AjazuddinAnil K ManthaRaj KumarAnkur KaulShubhra ChaturvediAnil K MishraUmesh GuptaPublished in: ACS applied bio materials (2020)
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 tumor-induced 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 .
Keyphrases
- drug delivery
- drug release
- cancer therapy
- cell cycle arrest
- cell death
- oxide nanoparticles
- atomic force microscopy
- reactive oxygen species
- pi k akt
- photodynamic therapy
- induced apoptosis
- breast cancer cells
- oxidative stress
- randomized controlled trial
- drug induced
- dna damage
- risk assessment
- deep learning
- emergency department
- clinical trial
- convolutional neural network
- diabetic rats
- open label
- double blind