METHODS: The designed nano- anticancer formulation was characterized thorough X-ray diffraction (XRD), Fourier transformed infrared (FTIR), transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) and Brunauer-Emmett-Teller (BET) methods. The nano- anticancer formulation (DTX- CaCO3NP) was evaluated for drug delivery properties thorough in vitro release study in human body simulated solution at pH 7.4 and intracellular lysosomal pH 4.8.
RESULTS: Characterization revealed the successful synthesis of DTX- CaCO3NP, which had a sustained release at pH 7.4. TEM showed uniformly distributed pleomorphic shaped pure aragonite particles. The highest entrapment efficiency (96%) and loading content (11.5%) were obtained at docetaxel to nanoparticles ratio of 1:4. The XRD patterns revealed strong crystallizations in all the nanoparticles formulation, while FTIR showed chemical interactions between the drug and nanoparticles with negligible positional shift in the peaks before and after DTX loading. BET analysis showed similar isotherms before and after DTX loading. The designed DTX- CaCO3NP had lower (p 0.05) effects at 48 h and 72 h. However, the DTX- CaCO3NP released less than 80% of bond DTX at 48 and 72 h but showed comparable effects with free DTX.
CONCLUSIONS: The results showed that the developed DTX- CaCO3NP released DTX slower at pH 7.4 and had comparable cytotoxicity with free DTX at 48 and 72 h in MCF-7 cells.
METHODS: Postbiotic metabolites (PM) produced by six strains of L. plantarum were determined for their antiproliferative and cytotoxic effects on normal human primary cells, breast, colorectal, cervical, liver and leukemia cancer cell lines via MTT assay, trypan blue exclusion method and BrdU assay. The toxicity of PM was determined for human and various animal red blood cells via haemolytic assay. The cytotoxicity mode was subsequently determined for selected UL4 PM on MCF-7 cells due to its pronounced cytotoxic effect by fluorescent microscopic observation using AO/PI dye reagents and flow cytometric analyses.
RESULTS: UL4 PM exhibited the lowest IC50 value on MCF-7, RG14 PM on HT29 and RG11 and RI11 PM on HL60 cell lines, respectively from MTT assay. Moreover, all tested PM did not cause haemolysis of human, dog, rabbit and chicken red blood cells and demonstrated no cytotoxicity on normal breast MCF-10A cells and primary cultured cells including human peripheral blood mononuclear cells, mice splenocytes and thymocytes. Antiproliferation of MCF-7 and HT-29 cells was potently induced by UL4 and RG 14 PM respectively after 72 h of incubation at the concentration of 30% (v/v). Fluorescent microscopic observation and flow cytometric analyses showed that the pronounced cytotoxic effect of UL4 PM on MCF-7 cells was mediated through apoptosis.
CONCLUSION: In conclusion, PM produced by the six strains of L. plantarum exhibited selective cytotoxic via antiproliferative effect and induction of apoptosis against malignant cancer cells in a strain-specific and cancer cell type-specific manner whilst sparing the normal cells. This reveals the vast potentials of PM from L. plantarum as functional supplement and as an adjunctive treatment for cancer.