Novel nano-vehicle for delivery and efficiency of anticancer auraptene against colon cancer cells

Abstract

The aim of this study is to devise, prepare and characterize nano encapsulated auraptene (AUR) and evaluate cytotoxic and apoptotic effects on HT-29 colon cancer cells. Herein, AUR nano formulations were prepared by triblock (PCL-PEG-PCL) and pentablock (PLA-PCL-PEG-PCL-PLA) biodegradable copolymers in order to increase AUR bioavailability as an anticancer agent. The preparation of nano particles (NPs) was done with rotor stator homogenization (RSH) and Ultrasonic homogenization (USH) methods. The physicochemical characteristics of prepared nanoparticles (NPs) were studied using HNMR, FTIR, GPC, DLS and SEM techniques. The smaller hydrodynamic size (110 nm) and polydispersity index (PDI: 0.288) as well as higher cellular uptake (89%) were observed in PB NPs rather than TB NPs. The highest cytotoxic and apoptotic effects were observed in AUR loaded PB NPs compared to AUR loaded TB NPs and free AUR obtained by MTT assay, cell cycle arrest, Annexin V-FITC, DAPI staining and RT-PCR techniques. Real time PCR results indicated that Bax /Bcl2 expression ratio as an apoptosis predicting criterion, in free AUR, AUR loaded TB and AUR loaded PB have increased 6, 9 and 13 times, respectively (p value < 0.05). In conclusion, using biodegradable nano-vehicles for sustained delivery of natural anti-cancer compounds may open new perspectives for treatment of cancer patients. NP preparation and characterization. Nano particles size, zeta potential and morphology. Table 1 summarized the size distribution, polydispersity index and zeta potential of TB and PB NPs prepared by RSH and USH methods, measured by DLS technique. Blank PB and TB NPs size prepared by RSH method were 170 and 308 nm, while size of NPs prepared by USH method were 109.8 and 314.5 nm, respectively. PDI values of PB and TB NPs prepared by RSH method were 0.805 and 0.675 while, this value for NPs prepared by USH methods were 0.288 and 0.192, respectively (Figs. S3-S10). Surface charge of TB and PB NPs which were prepared by RSH method were −26.4 mV and −19.6 mV and for TB and PB NPs which were prepared by USH method were −17.5 mV and −9.26 mV. Due to the superiority of USH compare to RSH method in terms of smaller size, narrower PDI and lower negative surface charge, we used USH method in rest of this study. Figures 5 and 6 show the SEM images of TB and PB NPs prepared by both RSH and USH methods. As it has been seen in the SEM images revealed that NPs real size were in the range of 10 nm to 50 nm also NPs had homo-dispersed spherical morphology. Scientific RepoRtS |(2020) 10:1606 | https://doi. Auraptene release.In the current study, the release of AUR from TB and PB NPS was studied over 120 h and the controlled-release potential was assessed (Fig. 7). The release data generated in this work indicated that in pH 7.4 environment over 24 h only 16.74% and 14.29% of the drug were released from AUR loaded PB and AUR loaded TB NPs respectively. Which in pH 5.4 environment AUR release from AUR loaded PB and AUR loaded TB NPs at the same time were 14.39% and 12.76% respe...

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