Skip to main content
SpringerLink
Log in

Preparation of oral nanoemulsion drug delivery system loaded with punicalagin: in vitro antibacterial activity, drug release, and cell safety studies

  • Article
  • Published:
Macromolecular Research Aims and scope Submit manuscript

Abstract

The objective of the present study was to develop a W/O/W nanoemulsion (NE) drug delivery system loaded with punicalagin (PGN) for oral delivery and evaluate its potential in antibacterial therapy. The W/O/W PGN-NE was prepared using a two-step process by combining ultrasonic with high-energy emulsification and subsequently characterized by its droplet size, zeta potential, and morphology. The PGN-NE was further evaluated for its pH, in vitro antibacterial activity, drug release property, and cytotoxicity. The results indicated the formation of spherical, nano-sized globules of PGN-NE had a mean particle size of 45.53 ± 2.2 nm, with a PDI value of 0.22 ± 0.028, zeta potential was −4.67 ± 0.88 mV, and pH value was 5.8. In vitro antibacterial activity studies showed a significantly higher antibacterial activity of PGN-NE in comparison to free PGN, suggesting that NE can effectively improve the antibacterial effect of natural pharmaceuticals. The drug release assay demonstrated that PGN was slowly released from the NE preparation and absorbed, helping to prolong the potency and improve the bioavailability of PGN. Cytotoxicity testing showed that PGN had reduced toxicity when encapsulated in NE. Thus, the developed NE formulation of PNG exhibited a greater potential for the slow-release effect delivery and in the treatment of microbial infections with favorable safety profile.

Graphical abstract

Micromorphology of W/O/W PGN nanoemulsion

The W/O/W PGN-NE are uniform in size and non-adhesive, with a size distribution of 28.214 to 141.772 nm and a mean size of 45.53 ± 2.2 nm, respectively, with a PDI value of 0.22 ± 0.028.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. P. Ilana et al., Making the hospital a safer place by sonochemical coating of all its textiles with antibacterial nanoparticles. Ultrason. Sonochem. 25, 82–88 (2015). https://doi.org/10.1016/j.ultsonch.2014.12.012

    Article  CAS  Google Scholar 

  2. A. Anna et al., A sonochemical technology for coating of textiles with antibacterial nanoparticles and equipment for its implementation. Mater. Lett. 96, 121–124 (2013). https://doi.org/10.1016/j.matlet.2013.01.041

    Article  CAS  Google Scholar 

  3. A. Mariscal et al., Antimicrobial effect of medical textiles containing bioactive fibres. Eur. J. Clin. Microbiol. Infect. Dis. 30, 227–232 (2011). https://doi.org/10.1007/s10096-010-1073-1

    Article  CAS  PubMed  Google Scholar 

  4. A. Haji, A. Shoushtari, Natural antibacterial finishing of wool fiber using plasma technology. Industria Textila 62(5), 244–247 (2011). https://doi.org/10.3993/tbis2011358

    Article  CAS  Google Scholar 

  5. R. Zhang et al., Antibiotic resistance as a global threat: evidence from China, Kuwait and the United States. Globalization Health 2, 6–20 (2006). https://doi.org/10.1186/1744-8603-2-6

    Article  PubMed  PubMed Central  Google Scholar 

  6. A.I. Dan, H. Diarmaid, Antibiotic resistance and its cost: is it possible to reverse resistance? Nat. Rev. Microbiol. 8, 260–271 (2010). https://doi.org/10.1038/nrmicro2319

    Article  CAS  Google Scholar 

  7. C. Liu et al., Antibacterial and antibiotic synergistic activities of the extract from Pithecellobium clypearia against clinically important multidrug-resistant gram-negative bacteria. Eur. J. Integr. Med. 32, 100999 (2019). https://doi.org/10.1016/j.eujim.2019.100999

    Article  Google Scholar 

  8. M.I. Ahmad et al., Pharkphoom Panichayupakaranant, Synergistic effect of α-mangostin on antibacterial activity of tetracycline, erythromycin, and clindamycin against acne involved bacteria. Chin. Herbal Med. 11(4), 412–416 (2019). https://doi.org/10.1016/j.chmed.2019.03.013

    Article  ADS  Google Scholar 

  9. S.A. Zacchino et al., SortinoPlant phenolics and terpenoids as adjuvants of antibacterial and antifungal drugs. Phytomedicine 37, 27–48 (2017). https://doi.org/10.1016/j.phymed.2017.10.018

    Article  CAS  PubMed  Google Scholar 

  10. W. Qian et al., Antibacterial and antibiofilm activity of ursolic acid against carbapenem-resistant enterobacter cloacae. J. Biosci. Bioeng. 129(5), 528–534 (2020)

    Article  CAS  PubMed  Google Scholar 

  11. E.M. Abdelfattah et al., Antibacterial, antifungal and antioxidant activity of total polyphenols of Withania frutescens.L. Bioorganic Chem.. 93, 103337–103346 (2019). https://doi.org/10.1016/j.bioorg.2019.103337

    Article  CAS  Google Scholar 

  12. A.Z. Susana et al., Plant phenolics and terpenoids as adjuvants of antibacterial and antifungal drugs. Phytomedicine 37, 27–48 (2017). https://doi.org/10.1016/j.phymed.2017.10.018

    Article  CAS  Google Scholar 

  13. L.T. Lin et al., Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry. BMC Microbiol. 13, 187 (2013). https://doi.org/10.1186/1471-2180-13-187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. T. Sachin et al., Rapid, enhanced and eco-friendly recovery of punicalagin from fresh waste pomegranate peels via aqueous ball milling. J. Clean. Prod. 228, 1238–1247 (2019). https://doi.org/10.1016/j.jclepro.2019.04.392

    Article  CAS  Google Scholar 

  15. M. Akansha et al., Nanoparticles of punicalagin synthesized from pomegranate (Punica granatum L.) with enhanced efficacy against human hepatic carcinoma cells. J. Clust. Sci. 33, 349–359 (2022). https://doi.org/10.1007/s10876-021-01979-9

    Article  CAS  Google Scholar 

  16. M. Labieniec, T.G. Gabryelak, Effects of tannins on Chinese hamster cell line B14. Mutat. Res. 539, 127–135 (2003). https://doi.org/10.1016/S1383-5718(03)00161-X

    Article  CAS  PubMed  Google Scholar 

  17. A. Debora, C., et al., Study of antimicrobial activity and atomic force microscopy imaging of the action mechanism of cashew tree gum. Carbohydr. Polym. 90(1), 270–274 (2012). https://doi.org/10.1016/j.carbpol.2012.05.034

    Article  CAS  Google Scholar 

  18. A. Mariana et al., Pomegranate and grape by-products and their active compounds: are they a valuable source for food applications? Trends Food Sci. Technol. 86, 68–84 (2019). https://doi.org/10.1016/j.tifs.2019.02.010

    Article  CAS  Google Scholar 

  19. A.A. Fouad et al., Punicalagin alleviates hepatotoxicity in rats challenged with cyclophosphamide. Environ. Toxicol. Pharmacol. 45, 158–162 (2016). https://doi.org/10.1016/j.etap.2016.05.031

    Article  CAS  PubMed  Google Scholar 

  20. F. Mo et al., Protective mechanism of punicalagin against endoplasmic reticulum stress in the liver of mice with type 2 diabetes mellitus. J. Funct. Foods. 56, 57–64 (2019). https://doi.org/10.1016/j.jff.2019.03.006

    Article  CAS  Google Scholar 

  21. G. Beatriz et al., Assessment of polyphenolic profile and antibacterial activity of pomegranate peel (Punica granatum) flour obtained from co-product of juice extraction. Food Control 59, 94–98 (2016). https://doi.org/10.1016/j.foodcont.2015.05.025

    Article  CAS  Google Scholar 

  22. S.H. Mun et al., Punicalagin suppresses methicillin resistance of Staphylococcus aureus to oxacillin. J. Pharmacol. Sci. 137, 317–323 (2018). https://doi.org/10.1016/j.jphs.2017.10.008

    Article  CAS  PubMed  Google Scholar 

  23. A.D. Smith et al., Pomegranate peel extract reduced colonic damage and bacterial translocation in a mouse model of infectious colitis induced by Citrobacter rodentium. Nutr. Res. 73, 27–37 (2020). https://doi.org/10.1016/j.nutres.2019.11.001

    Article  CAS  PubMed  Google Scholar 

  24. N. Badawi et al., Pomegranate extract-loaded solid lipid nanoparticles: design, optimization, and in vitro cytotoxicity study. Int. J. Nanomed. 13, 1313–1326 (2018). https://doi.org/10.2147/IJN.S154033

    Article  CAS  Google Scholar 

  25. V. Sanna et al., Nanoformulation of natural products for prevention and therapy of prostate cancer. Cancer Lett. 334(1), 142–151 (2013). https://doi.org/10.1016/j.canlet.2012.11.037

    Article  CAS  PubMed  Google Scholar 

  26. A.B. Shirode et al., Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention. Int. J. Nanomed. 10, 475–484 (2015). https://doi.org/10.2147/IJN.S65145

    Article  CAS  Google Scholar 

  27. L. Yang et al., Bio-inspired dual-adhesive particles from microfluidic electrospray for bone regeneration. Nano Res. 16, 5292–5299 (2023). https://doi.org/10.1007/s12274-022-5202-9

    Article  CAS  ADS  Google Scholar 

  28. L. Lanjie et al., Angiogenic microspheres for the treatment of a thin endometrium. ACS Biomater. Sci. Eng. 7, 4914–4920 (2021). https://doi.org/10.1021/acsbiomaterials.1c00615

    Article  CAS  Google Scholar 

  29. Z. Lin et al., Antimicrobial curcumin nanoparticles downregulate joint inflammation and improve osteoarthritis. Macromol. Res. (2023). https://doi.org/10.1007/s13233-023-00196-9

    Article  Google Scholar 

  30. W. Huan et al., Biomimetic enzyme cascade reaction system in microfluidic electrospray microcapsules. Sci. Adv. 4, 2816–2823 (2018). https://doi.org/10.1126/sciadv.aat2816

    Article  CAS  ADS  Google Scholar 

  31. M.G.D. Silva et al., Nanoemulsion composed of 10-(4,5-dihydrothiazol-2-yl)thio)decan-1-ol), a synthetic analog of 3-alkylpiridine marine alkaloid: development, characterization, and antimalarial activity. Eur. J. Pharm. Sci. 151, 105382–105391 (2020). https://doi.org/10.1016/j.ejps.2020.105382

    Article  CAS  PubMed  Google Scholar 

  32. R.A. Schuenck-Rodrigues et al., Development, characterization and photobiological activity of nanoemulsion containing zinc phthalocyanine for oral infections treatment. J. Photochem. Photobiol. B. 211, 112010–112021 (2020). https://doi.org/10.1016/j.jphotobiol.2020.112010

    Article  CAS  PubMed  Google Scholar 

  33. B.M. Altaani et al., Oral delivery of teriparatide using a nanoemulsion system: design, in vitro and in vivo evaluation. Pharm. Res. 37, 80–95 (2020). https://doi.org/10.1016/j.jphotobiol.2020.112010

    Article  CAS  PubMed  Google Scholar 

  34. M. Handa et al., Therapeutic potential of nanoemulsions as feasible wagons for targeting Alzheimer’s disease. Drug Discov. Today 26, 2881–2888 (2021). https://doi.org/10.1016/j.drudis.2021.07.020

    Article  CAS  PubMed  Google Scholar 

  35. N. Vasdev et al., Rosemary oil low energy nanoemulsion: Optimization, µrheology, in silico, in vitro and Ex vivo characterization. J. Biomat. Sci. Polym. Edition. 33, 1901–1923 (2022). https://doi.org/10.1080/09205063.2022.2088527

    Article  CAS  Google Scholar 

  36. T. Li et al., Preparation and properties of water-in-oil shiitake mushroom polysaccharide nanoemulsion. Int. J. Biol. Macromol. 140, 343–349 (2019). https://doi.org/10.1016/j.ijbiomac.2019.08.134

    Article  CAS  PubMed  Google Scholar 

  37. Y. Singh et al., Nanoemulsion: concepts, development and applications in drug delivery. J. Control. Release 252, 28–49 (2017). https://doi.org/10.1016/j.jconrel.2017.03.008

    Article  CAS  PubMed  Google Scholar 

  38. Badwan, A., et al., “Oral Delivery of Protein Drugs Using Microemulsion European”. Patent EP1797870, 2007.

  39. Shin,S.H., et al.:Tracking perfluorocarbon nanoemulsion delivery by 19F MRI for precise high intensity focused ultrasound tumor ablation. Theranostics. 7, 562–572(2017). https://doi.org/10.7150/thno.16895

  40. L. Guo et al., Preliminary evaluation of a novel oral delivery system for rhPTH1-34: in vitro and in vivo. Int. J. Pharm. 420(1), 172–179 (2011). https://doi.org/10.1016/j.ijpharm.2011.08.029

    Article  CAS  PubMed  Google Scholar 

  41. W. Li et al., A bufadienolide-loaded submicron emulsion for oral administration: stability, antitumor efficacy and toxicity. Int. J. Pharm. 479(1), 52–62 (2015). https://doi.org/10.1016/j.ijpharm.2014.12.054

    Article  CAS  PubMed  Google Scholar 

  42. G. Lida et al., Effective Inhibition and eradication of Pseudomonas aeruginosa bioflms by Satureja khuzistanica essential oil nanoemulsion. J. Drug Deliv. Sci Technol. 61, 102260–102268 (2021). https://doi.org/10.1016/j.jddst.2020.102260

    Article  CAS  Google Scholar 

  43. L. HsuehYu et al., Preparation and evaluation of Cordyceps militaris polysaccharide- and sesame oil-loaded nanoemulsion for the treatment of candidal vaginitis in mice. Biomed. Pharmacother. 167, 115506–115517 (2023). https://doi.org/10.1016/j.biopha.2023.115506

    Article  CAS  Google Scholar 

  44. A. Hairul et al., Preparation of nano-sized particles from bacterial cellulose using ultrasonication and their characterization. Carbohyd. Polym. 191, 161–167 (2018). https://doi.org/10.1016/j.carbpol.2018.03.026

    Article  CAS  Google Scholar 

  45. K. Maheshika et al., Probe ultrasonication synthesis of Eu2O3-doped 2D WS2 nanosheets for highly selective and sensitive quantification of human catecholamines by fluorescent quenching and shifting. Mater. Res. Bull. 170, 112555–112564 (2024). https://doi.org/10.1016/j.materresbull.2023.112555

    Article  CAS  Google Scholar 

  46. W. Jun et al., Formulation of water-in-oil-in-water (W/O/W) emulsions containing trans-resveratrol. RSC Adv. 7, 35917–35924 (2017). https://doi.org/10.1039/c7ra05945k

    Article  CAS  Google Scholar 

  47. C. CLSI :Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fourth Informational Supplement, M100-S24.2014.

  48. T. Mosmann, Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65(1–2), 55–63 (1983). https://doi.org/10.1016/0022-1759(83)90303-4

    Article  CAS  PubMed  Google Scholar 

  49. I.V. Krishna et al., Cytotoxic studies of anti-neoplastic drugs on human lymphocytes in vitro studies. Cancer Biomark. 5, 261–272 (2009). https://doi.org/10.3233/CBM-2009-0111

    Article  CAS  PubMed  Google Scholar 

  50. H. Rachmawati et al., Curcumin nanoemulsion for transdermal application: formulation and evaluation. Drug Dev. Ind. Pharm. 41, 560–566 (2015). https://doi.org/10.3109/03639045.2014.884127

    Article  CAS  PubMed  Google Scholar 

  51. D.S. Santos et al., Oral delivery of fsh oil in oil-in-water nanoemulsion: development, colloidal stability and modulatory effect on in vivo inflammatory induction in mice. Biomed. Pharmacotherapy. 133, 110980–110997 (2021). https://doi.org/10.1016/j.biopha.2020.110980

    Article  CAS  Google Scholar 

  52. S.K. Paudel et al., Antimicrobial activity of cinnamon oil nanoemulsion against Listeria monocytogenes and Salmonella spp. on melons. LWT Food Sci. Technol. 111, 682–687 (2019). https://doi.org/10.1016/j.lwt.2019.05.087

    Article  CAS  Google Scholar 

  53. K.M.M. Leao et al., Physicochemical characterization and antimicrobial activity in novel systems containing buriti oil and structured lipids nanoemulsions. Biotechnology Reports. 24, e00365 (2019). https://doi.org/10.1016/j.btre.2019.e00365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. W. Liping et al., Preparation of starch-based nanoemulsion for sustained release and enhanced bioaccessibility of quercetin. Colloids Surfaces A: Physicochemical Eng. 665, 131218–131230 (2023). https://doi.org/10.1016/j.colsurfa.2023.131218

    Article  CAS  Google Scholar 

  55. Li. Meiting, Optimization of preparation conditions and in vitro sustained-release evaluation of a novel nanoemulsion encapsulating unsaturated guluronate oligosaccharide. Carbohyd. Polym. 264, 118047–118057 (2021). https://doi.org/10.1016/j.carbpol.2021.118047

    Article  CAS  Google Scholar 

  56. R.B. Rigon et al., Solid lipid nanoparticles optimized by 2(2) factorial design for skin administration: Cytotoxicity in NIH3T3 fibroblasts. Colloids Surfaces B-Biointerfaces. 171, 501–505 (2018). https://doi.org/10.1016/j.colsurfb.2018.07.065

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was based on the work supported by grants from the Natural Science Research of Jiangsu Higher Education Institutions of China (Grant No.19KJD230002), Scientific Research Foundation of Graduate School of Jiangsu Agri-animal Husbandry Vocational College, China (Grant No. NSFZP201902), and Animal medicine science and technology innovation team of Jiangsu Agri-Animal Husbandry Vocational College (Grant No. NSF2021TC02).

Author information

Authors and Affiliations

  1. Department of Pharmacy, Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, 225300, People’s Republic of China

    Fei-Fei Shi, Yu-Juan Mao, Ying Wang & Hai-Feng Yang

Authors
  1. Fei-Fei Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu-Juan Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hai-Feng Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hai-Feng Yang.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shi, FF., Mao, YJ., Wang, Y. et al. Preparation of oral nanoemulsion drug delivery system loaded with punicalagin: in vitro antibacterial activity, drug release, and cell safety studies. Macromol. Res. 32, 243–252 (2024). https://doi.org/10.1007/s13233-023-00224-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13233-023-00224-8

Keywords

Search

Navigation