Modified xanthan gum-based gel of curcumin and copper nanoparticles prepared from Tinospora cordifolia for wound therapy

The aim. The synthesis of nanoparticles through green methods is a biologically safe, cost-effective and environmentally friendly approach. This study focuses on the green synthesis of copper nanoparticles using aqueous stem extract of Tinospora cordifolia. Additionally, this research explores the formulation of an acetyl amine-modified xanthan gum-based gel incorporating curcumin and a solution of Cu⁺⁺ nanoparticles, and investigates its wound healing activity.

Materials and methods. The shade-dried stem of Tinospora cordifolia was extracted with distilled water, which serves as a bio-reducing agent for the synthesis of Cu⁺⁺ nanoparticles. Copper sulphate was added to the extract at room temperature using a magnetic stirrer. The visual color change during the addition indicates the formation of nanoparticles, which was further confirmed by UV spectroscopy and particle size analysis. The  modified xanthan gum-based gel formulation was  prepared using curcumin and a solution of Cu⁺⁺ nanoparticles, and its wound healing activity was evaluated using the excision method, along with antimicrobial activity assessed by the cup and plate method.

Results and discussion. UV absorption was observed at 261 nm, and the particle size was measured at 188 nm, confirming the formation of nanoparticles. The gel containing curcumin and  Cu⁺⁺ nanoparticles was prepared using modified xanthan gum. The nanocomposite exhibited significant antimicrobial activity against gram-positive bacteria compared to gram-negative bacteria. The group treated with the modified xanthan gum-based curcumin and nano copper composite demonstrated significant wound closure by day 16±2.

Conclusion. The  synthesis of  Cu⁺⁺ nanoparticles using Tinospora cordifolia and the formulation of a gel with modified xanthan gum and curcumin as a drug were successfully achieved. The  gel formulation demonstrated significant antibacterial and wound healing activities, attributed to synergistic effect of Tinospora cordifolia, curcumin, and Cu⁺⁺ nanoparticles.

1. De Kraker ME, Stewardson AJ, Harbarth S. Will 10 million people die a year due to antimicrobial resistance by 2050? PLoS Med. 2016; 13(11): e1002184. doi: 10.1371/journal.pmed.1002184

2. Nair A, Mallya R, Suvarna V, Khan TA, Momin M, Omri A. Nanoparticles-attractive carriers of antimicrobial essential oils. Antibiotics (Basel). 2022; 11(1): 108. doi: 10.3390/antibiotics11010108

3. Singh P, Kim YJ, Zhang D, Yang DC. Biological synthesis of nanoparticles from plants and microorganisms. Trends Biotechnol. 2016; 34(7): 588-599. doi: 10.1016/j.tibtech.2016.02.006

4. Zhang D, Ma XL, Gu Y, Huang H, Zhang GW. Green synthesis of metallic nanoparticles and their potential applications to treat cancer. Front Chem. 2020; 8: 799. doi: 10.3389/fchem.2020.00799

5. Jamkhande PG, Ghule NW, Bamer AH, Kalaskar MG. Metal nanoparticles synthesis: An overview on methods of preparation, advantages and disadvantages, and applications. J Drug Deliv Sci Technol. 2019; 53: 101174. DOI: 10.1016/J.JDDST.2019.101174

6. Qamar H, Rehman S, Chauhan DK, Tiwari AK, Upmanyu V. Green synthesis, characterization and antimicrobial activity of copper oxide nanomaterial derived from momordica charantia. Int J Nanomedicine. 2020; 15: 2541-2553. doi: 10.2147/IJN.S240232

7. Thakore SI, Nagar PS, Jadeja RN, Thounaojam M, Devkar RV, Rathore PS. Sapota fruit latex mediated synthesis of Ag, Cu mono and bimetallic nanoparticles and their in vitro toxicity studies. Arab J Chem. 2019; 12(5): 694-700. doi: 10.1016/j.arabjc.2014.12.042

8. Gawande MB, Goswami A, Felpin FX, Asefa T, Huang X, Silva R, et al. Cu and Cu-based nanoparticles: Synthesis and applications in catalysis. Chem Rev. 2016; 116(6): 3722-3811. doi: 10.1021/acs.chemrev.5b00482

9. Sunday AA, Abel KO, Seyifunmi CO, Dayo FL. Green chemistry approach towards the synthesis of copper nanoparticles and its potential applications as therapeutic agents and environmental control. Curr Res Green Sustain Chem. 2021; 4: 100176. doi: 10.1016/j.crgsc.2021.100176

10. Amer MW, Awwad AM. Green synthesis of copper nanoparticles by Citrus limon fruits extract, characterization and antibacterial activity. Chem Int. 2021; 7(1): 1-8.

11. Ismail MIM. Green synthesis and characterizations of copper nanoparticles. Mater Chem Phys. 2020; 240: 122283. doi: 10.1016/j.matchemphys.2019.122283

12. Chandraker SK, Lal M, Ghosh MK, Tiwari V, Ghorai TK, Shukla R. Green synthesis of copper nanoparticles using leaf extract of Ageratum houstonianum Mill. and study of their photocatalytic and antibacterial activities. Nano Ex. 2020; 1(1): 010033. doi: 10.1088/2632-959X/ab8e99

13. Singh S. Green synthesis and characterization of copper nanoparticles using Madhunashini leaf extract and evaluation of its antibacterial property. Int J Innov Res Technol. 2018; 4(8): 307-312.

14. Mohindru JJ, Garg UK. Green synthesis of copper nanoparticles using tea leaf extract. Int J Eng Sci Res Technol. 2017; 6(7): 307-311. doi: 10.5281/zenodo.827502

15. Hariprasad S, Bai SG, Santhoshkumar J, Madhu CH, Sravani D. Green synthesis of copper nanoparticles by Arevalanata leaves extract and their antimicrobial activity. Int J Chem Tech Res. 2016; 9: 98-105.

16. Chung IM, Abdul Rahuman A, Marimuthu S, Kirthi AV, Anbarasan K, Padmini P, et al. Green synthesis of copper nanoparticles using Eclipta prostrata leaves extract and their antioxidant and cytotoxic activities. Exp Ther Med. 2017; 14(1): 18-24. doi: 10.3892/etm.2017.4466

17. Sharma P, Pant S, Poonia P, Kumari S., Dave V., Sharma S. Green synthesis of colloidal copper nanoparticles capped with Tinospora cordifolia and its application in catalytic degradation in textile dye: An ecologically sound approach. J Inorg Organomet Polym. 2018; 28: 2463-2472. doi: 10.1007/s10904-018-0933-5

18. Lakshmi Tulasi S, Swamy A, Peddi P, Usha Rani N. Plant based biosynthesis of copper nanoparticles and its efficacy on seed viability and seedling growth in peanut (Arachis hypogaea Linn.) Asian J Chem. 2022; 34(2), 415-422. doi: 10.14233/ajchem.2022.23553

19. Kshirsagar PS, Mote DS. Green synthesis of copper nanoparticles using Mentha spicata leaves extract. EurJ Pharm Med Res. 2021; 8(8): 398-404.

20. Keerthika E, Ishwarya K, Jayashree L, Maripandian S, Nivetha, Irivichetty Sai Chandana. Potential antibacterial activity of green synthesized copper nanoparticles and its characterization. Int J Curr Res Rev. 2021; 13(19): 27-32. doi: 10.31782/IJCRR.2021.131929

21. Vincent M, Duval RE, Hartemann P, Engels-Deutsch M. Contact killing and antimicrobial properties of copper. J Appl Microbiol. 2018; 124(5): 1032-1046. doi: 10.1111/jam.13681

22. Ma X, Zhou S, Xu X, Du Q. Copper-containing nanoparticles: Mechanism of antimicrobial effect and application in dentistry – a narrative review. Front Surg. 2022; 9: 905892. doi: 10.3389/fsurg.2022.905892

23. Arendsen LP, Thakar R, Sultan AH. The use of copper as an antimicrobial agent in health care, including obstetrics and gynecology. Clin Microbiol Rev. 2019; 32(4): e00125-18. doi: 10.1128/CMR.00125-18

24. Alqahtani MS, Alqahtani A, Kazi M, Ahmad MZ., Alahmari A, Alsenaidy MA, et al. Wound-healing potential of curcumin loaded lignin nanoparticles. J Drug Deliv Sci Technol. 2020; 60: 102020. doi: 10.1016/j.jddst.2020.102020

25. Prakash MVD, Sampath S, Amudha K, Nadeem A, Lopes BS, Durga B., et al. Eco-friendly green synthesis of copper nanoparticles from Tinospora cordifolia leaves: Optical properties with biological evaluation of anti-microbial, anti-inflammatory and anti-oxidant applications. Mater Technol. 2023; 38(1). doi: 10.1080/10667857.2023.2247908

26. Jadhav RL, Patil MV, Shaikh SN. Synthesis, characterization and in vivo evaluation of poly sulfoxy amine grafted xanthan gum. IntJ Lifesci Pharm Res. 2020; 10(3): 20-28. doi: 10.22376/ijpbs/lpr.2020.10.3.P20-28

27. Jadhav RL, Beloshe P, Yadav AV, Patil MV, ShaikhSN. Design, development andcharacterization ofmodified xanthan gum based novel in-situ gel of ciprofloxacin hydrochloride forophthalmic drug delivery. Asian J Pharmaceut. 2020; 14(2): 236-246. doi: 10.22377/ajp.v14i2.3619

28. Jadhav RL, Yadav AV, Patil MV. Poly sulfoxy amine grafted chitosan as bactericidal dressing for wound healing. Asian J Chem. 2019; 31(12): 127-132. doi: 10.14233/ajchem.2020.22300

29. Salehi B, Rodrigues CF, Peron G, Dall’Acqua S, SharifiRad J, Azmi L, et al. Curcumin nanoformulations for antimicrobial and wound healing purposes. Phytother Res. 2021; 35(5): 2487- 2499. doi: 10.1002/ptr.6976

30. Shefa AA, Sultana T, Park MK, Lee SY, Gwon JG, Lee BT. Curcumin incorporation into an oxidized cellulose nanofiber-polyvinyl alcohol hydrogel system promotes wound healing. Mater Des. 2020; 186: 108313. doi: 10.1016/j.matdes.2019.108313