Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Sep 5;8(9):375.
doi: 10.3390/antiox8090375.

Polydatin Encapsulated Poly [Lactic-co-glycolic acid] Nanoformulation Counteract the 7,12-Dimethylbenz[a] Anthracene Mediated Experimental Carcinogenesis through the Inhibition of Cell Proliferation

Sankaran Vijayalakshmi  1 , Arokia Vijaya Anand Mariadoss  1 , Vinayagam Ramachandran  1 , Vijayakumar Shalini  1 , Balupillai Agilan  1 , Casimeer C Sangeetha  2 , Periyasamy Balu  3 , Venkata Subbaih Kotakadi  4 , Venkatachalam Karthikkumar  5 , David Ernest  6
Affiliations

Polydatin Encapsulated Poly [Lactic-co-glycolic acid] Nanoformulation Counteract the 7,12-Dimethylbenz[a] Anthracene Mediated Experimental Carcinogenesis through the Inhibition of Cell Proliferation

Sankaran Vijayalakshmi et al. Antioxidants (Basel). .

Abstract

In the present study, the authors have attempted to fabricate Polydatin encapsulated Poly [lactic-co-glycolic acid] (POL-PLGA-NPs) to counteract 7,12-dimethyl benzyl anthracene (DMBA) promoted buccal pouch carcinogenesis in experimental animals. The bio-formulated POL-PLGA-NPs were characterized by dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRD) pattern analysis, and transmission electron microscope (TEM). In addition, the nano-chemopreventive potential of POL-PLGA-NPs was assessed by scrutinizing the neoplastic incidence and analyzing the status of lipid peroxidation, antioxidants, phase I, phase II detoxification status, and histopathological changes and in DMBA-treated animals. In golden Syrian hamsters, oral squamous cell carcinoma (OSCC) was generated by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. After 100% tumor formation was observed, high tumor volume, tumor burden, and altered levels of biochemical status were observed in the DMBA-painted hamsters. Intra-gastric administration of varying concentration of POL-PLGA-NPs (7.5, 15, and 30 mg/kg b.wt) to DMBA-treated hamsters assumedly prevents oncological incidences and restores the status of the biochemical markers. It also significantly enhances the apoptotic associated and inhibits the cancer cell proliferative markers expression (p53, Bax, Bcl-2, cleaved caspase 3, cyclin-D1). The present study reveals that POL-PLGA-NPs is a penitential candidate for nano-chemopreventive, anti-lipid peroxidative, and antioxidant potential, and also has a modulating effect on the phase I and Phase II detoxification system, which is associated with reduced cell proliferation and induced apoptosis in experimental oral carcinogenesis.

Keywords: PLGA; antioxidant; apoptosis; cell proliferation; nanoformulation; polydatin.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Dynamic light scattering (DLS) analysis (mean particle size, polydispersity index and Zeta potential) of poly-lactic-co-glycolic acid nanoparticles (PLGA-NPs) and POL-PLGA-NPs. POL-PLGA-NPs has 187.3 (average size), 0.256 (PDI index), and −23.8 mV of Zeta potential.
Figure 2
Figure 2
Transmission electron microphotograph of POL-PLGA-NPs. It shows the smooth surface without agglomeration and NPs appeared spherical in shape, with an average size of 105 to 200 nm.
Figure 3
Figure 3
Atomic force microscopy analysis of green synthesized POL-PLGA-NPs. The results disclose that biosynthesized NPs appears to be spherical in shape by the seeing the nanoparticle’s topology and morphology of 2D image (A). Nova-Px 3.2.0.rev soft ware provided by NT-MDT was used to detect the grain size of the AFM image. An analysis of the results reveals that the NPs are varied in size that is 150 nm ± 10 nm to 200 nm ± 10 nm, we have also carried out grain analysis of the AFM 3D image using Nova-Px 3.2.0.rev software (B). Whereas the average size of the grains was found to be 160 ± 10 nm nm by using grain analysis (C&D).
Figure 4
Figure 4
FTIR spectrum of polydatin, PLGA and POL-PLGA-NPs. FTIR spectrum of POL-PLGA-NPs showing the peaks of 3503, 3485 cm−1 shift to a lower frequency at 3395 cm−1 due to the encapsulation of PLGA.
Figure 5
Figure 5
XRD pattern of polydatin, PLGA, and POL-PLGA-NPs. POL-PLGA-NPs showings peaks in 14.18°, 21.98°, and 35.62° indicates the entrapment of polydatin in synthesized PLGA nanoparticles.
Figure 6
Figure 6
In vitro release pattern of polydatin loaded PLGA nanoparticles. Burst and fast releasing pattern were recorded in pH 4.8, Almost 68% polydatin was released from the nanoformulation.
Figure 7
Figure 7
Effects of POL-PLGA-NPs on 7, 12-dimethyl benzyl anthracene (DMBA) -induced changes in the activity of thiobarbituric acid reactive substances (TBARS), Lipid hydroperoxides (LOOH), and CD. Values are expressed as mean ± SD (n = 6). * significantly differ from control group (p < 0.05), ** Significantly differ from DMBA group (p < 0.001), *** significantly differ from DMBA group (p < 0.05) (One-way ANOVA).
Figure 8
Figure 8
Effects of POL-PLGA-NPs on DMBA induced changes in the activity of enzymatic antioxidants. Values are expressed as mean ± SD (n = 6). * Significantly differ from control group (p < 0.05), ** Significantly differ from DMBA group (p < 0.001), *** significantly differ from DMBA group (p < 0.05).
Figure 9
Figure 9
Effects of POL-PLGA-NPs on DMBA induced changes in the level of non-enzymatic antioxidants. Values are expressed as mean ± SD (n = 6). * Significantly differ from control group (p < 0.05), ** Significantly differ from DMBA group (p < 0.001), *** Significantly differ from DMBA group (p < 0.05) (Oneway ANOVA).
Figure 10
Figure 10
Modulating effects of POL-PLGA-NPs on DMBA induced Xenobiotic metabolizing enzymes. Values are expressed as mean ± SD (n = 6). * significantly differ from control group (p < 0.05), ** significantly differ from DMBA group (p < 0.001), *** significantly differ from DMBA group (p < 0.05) (One-way ANOVA).
Figure 11
Figure 11
Histopathological analysis of buccal tissue of control and experimental animals (10x). Control and POL-PLGA-NPs showing normal architecture. DMBA alone treated sections showing a well-defined squamous cell carcinoma with hyper chromatic nuclei containing epithelial and keratin pearls. DMBA+POL-PLGA-NPs showing a mild to moderate dysplasia and hyperplasia.
Figure 12
Figure 12
Immunoblot analysis of mutant p53, bax, Bcl-2, cleaved caspase-3, and cyclin D1 in control an experimental animal. 1-Control; 2-DMB; 3-DMBA+POL-PLGA-NPs (7.5 mg/kg b.wt.); 4-DMBA +POL-PLGA-NPs (15 mg/kg b.wt.); 5-DMBA +POL-PLGA-NPs (30 mg/kg b.wt.); 6-POL-PLGA-NP alone (30 mg/kg b.wt.). POL-PLGA-NPs enhance the apoptotic mediators such as Bax, cleaved caspase-3 and inhibit p53, Bcl-2 and cyclin-D1 expressions in a dose-dependent manner. Bar diagram represents the proteins expression; each bar represents the mean ± SD of three independent analysis.
Scheme 1
Scheme 1
Proposed mechanism involved in the polydatin loaded PLGA nanoparticles enhance the apoptosis and inhibit the cell proliferation in DMBA induced experimental carcinogenesis.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Gunasheela D., Menon J., Ashwin N. Strategies for fertility preservation in young patients with cancer. Onco Fertil. J. 2018;1:86. doi: 10.4103/tofj.tofj_4_18. - DOI - PMC - PubMed
    1. Arem H., Loftfield E. Cancer Epidemiology: A Survey of modifiable risk factors for prevention and survivorship. Am. J. Lifestyle Med. 2017;12:200–210. doi: 10.1177/1559827617700600. - DOI - PMC - PubMed
    1. Jethwa A.R., Khariwala S.S. Tobacco-related carcinogenesis in head and neck cancer. Cancer Metastasis Rev. 2017;36:411–423. doi: 10.1007/s10555-017-9689-6. - DOI - PMC - PubMed
    1. Romero-Perez A.I., Ibern-Gomez M., Lamuela-Raventos R.M., de La Torre-Boronat M.C. Piceid, the major resveratrol derivative in grape juices. J. Agric. Food Chem. 1999;47:1533–1536. doi: 10.1021/jf981024g. - DOI - PubMed