Silver nanoparticle microemulsion as a novel localized antimicrobial therapy: Formulation, efficacy, and safety evaluation

Main Article Content

Niratcha Chaisomboon
Teerawat Nitichaikulvattana
Hathairat Lekatana
Chanida Chantim
Nattakanwadee Khumpirapang
Prayuth Poowaruttanawiwit

Keywords

Silver nanoparticles, microemulsion, antimicrobial resistance, formulation, cytotoxicity, localized therapy

Abstract

Background: The increasing prevalence of antimicrobial resistance necessitates the development of alternative therapeutic strategies. Silver nanoparticles (AgNPs) have demonstrated broad-spectrum antimicrobial activity, yet formulation challenges limit their clinical translation. This study aims to develop and evaluate an AgNP microemulsion as a novel localized antimicrobial therapy, focusing on its formulation stability, antimicrobial efficacy, and biocompatibility. Methods: A silver nanoparticle microemulsion was formulated using a bottom-up synthesis approach, stabilized with polyvinyl alcohol (PVA) and Tween 80, and characterized for particle size, zeta potential, and UV-visible spectroscopy. Antimicrobial efficacy was assessed against Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus mutans using disk diffusion and broth dilution assays. Cytotoxicity was evaluated in L929 fibroblast cells using the MTT assay to establish a therapeutic window. Results: The AgNP microemulsion exhibited a mean particle size of 175.97 ± 0.97 nm, with a zeta potential of -1.06 ± 0.42 mV, indicating moderate colloidal stability. UV-visible spectroscopy confirmed nanoparticle formation, with a plasmon resonance peak at 250 ± 0.42 nm. Antimicrobial testing revealed limited efficacy, with inhibition zones of 9.11 mm (S. aureus), 8.93 mm (P. aeruginosa), and 9.04 mm (S. mutans), significantly lower than 0.2% chlorhexidine. MIC and MBC values exceeded 0.7 mg/mL, suggesting suboptimal bactericidal potency. Cytotoxicity studies demonstrated >70% cell viability at concentrations ≤16 µg/mL, but significant toxicity at 32 µg/mL, indicating a narrow therapeutic window.Conclusion: This study highlights the potential of AgNP microemulsions as a localized antimicrobial alternative but emphasizes the need for formulation optimization to enhance bactericidal efficacy while minimizing cytotoxicity. Future studies should explore surface modifications, synergistic agents, and controlled-release strategies to improve clinical applicability.

Abstract 114 | PDF Downloads 69

References

1. Oliveira M, Antunes W, Mota S, et al. An overview of the recent advances in antimicrobial resistance. Microorganisms. 2024;12(9):1920. doi:10.3390/microorganisms12091920
2. Salam MA, Al-Amin MY, Salam MT, et al. Antimicrobial resistance: A growing serious threat for global public health. Healthcare (Basel). 2023;11(13):1946. doi:10.3390/healthcare11131946
3. Muteeb G, Rehman MT, Shahwan M, et al. Origin of antibiotics and antibiotic resistance, and their impacts on drug development: A narrative review. Pharmaceuticals (Basel). 2023;16(11):1615. doi:10.3390/ph16111615
4. Selvarajan R, Obize C, Sibanda T, et al. Evolution and emergence of antibiotic resistance in given ecosystems: Possible strategies for addressing the challenge of antibiotic resistance. Antibiotics (Basel). 2022;12(1):28. doi:10.3390/antibiotics12010028
5. Downes KJ, Goldman JL. Too much of a good thing: Defining antimicrobial therapeutic targets to minimize toxicity. Clin Pharmacol Ther. 2021;109(4):905-917. doi:10.1002/cpt.2190
6. Ipe DS, Kumar PTS, Love RM, et al. Silver nanoparticles at biocompatible dosage synergistically increases bacterial susceptibility to antibiotics. Front Microbiol. 2020;11:1074. doi:10.3389/fmicb.2020.01074
7. Alotaibi AM, Alsaleh NB, Aljasham AT, et al. Silver nanoparticle-based combinations with antimicrobial agents against antimicrobial-resistant clinical isolates. Antibiotics (Basel). 2022;11(9):1219. doi:10.3390/antibiotics11091219
8. Parvin N, Joo SW, Mandal TK. Nanomaterial-based strategies to combat antibiotic resistance: Mechanisms and applications. Antibiotics (Basel). 2025;14(2):207. doi:10.3390/antibiotics14020207
9. Hashim M, Mujahid H, Hassan S, et al. Implication of nanoparticles to combat chronic liver and kidney diseases: Progress and perspectives. Biomolecules. 2022;12(10):1337. doi:10.3390/biom12101337
10. More PR, Pandit S, Filippis A, et al. Silver nanoparticles: Bactericidal and mechanistic approach against drug resistant pathogens. Microorganisms. 2023;11(2):369. doi:10.3390/microorganisms11020369
11. Pradhan D, Biswasroy P, Goyal A, et al. Recent advancement in nanotechnology-based drug delivery system against viral infections. AAPS PharmSciTech. 2021;22(1):47. doi:10.1208/s12249-020-01908-5
12. Nikolaev B, Yakovleva L, Fedorov V, et al. Nano- and microemulsions in biomedicine: From theory to practice. Pharmaceutics. 2023;15(7):1989. doi:10.3390/pharmaceutics15071989
13. Jacob S, Kather FS, Boddu SHS, et al. Innovations in nanoemulsion technology: Enhancing drug delivery for oral, parenteral, and ophthalmic applications. Pharmaceutics. 2024;16(10):1333. doi:10.3390/pharmaceutics16101333
14. Rauf S, Hameed H, Tariq M, et al. Phytochemical-mediated synthesis and characterization of silver nanoparticles using Mirabilis jalapa leaf extract and their antibacterial. Microsc Res Tech. 2025. doi:10.1002/jemt.24801
15. Xing Y, Liao X, Liu X, et al. Characterization and antimicrobial activity of silver nanoparticles synthesized with the peel extract of mango. Materials (Basel). 2021;14(19):5878. doi:10.3390/ma14195878
16. Kiarashi M, Mahamed P, Ghotbi N, et al. Spotlight on therapeutic efficiency of green synthesis metals and their oxide nanoparticles in periodontitis. J Nanobiotechnology. 2024;22(1):21. doi:10.1186/s12951-023-02284-5
17. Ferraz CC, Gomes BP, Zaia AA, et al. Comparative study of the antimicrobial efficacy of chlorhexidine gel, chlorhexidine solution and sodium hypochlorite as endodontic irrigants. Braz Dent J. 2007;18(4):294-298. doi:10.1590/s0103-64402007000400004
18. Nia AF, Ataei M, Zeighami H. A comparative study on the antimicrobial activity of irreversible hydrocolloid mixed with silver nanoparticles and chlorhexidine. Dent Res J (Isfahan). 2020;17(2):120-125.
19. Charannya S, Duraivel D, Padminee K, et al. Comparative evaluation of antimicrobial efficacy of silver nanoparticles and 2% chlorhexidine gluconate when used alone and in combination assessed using agar diffusion method: An in vitro study. Contemp Clin Dent. 2018;9(Suppl 2):S204-S209. doi:10.4103/ccd.ccd_869_17
20. Liao C, Li Y, Tjong SC. Bactericidal and cytotoxic properties of silver nanoparticles. Int J Mol Sci. 2019;20(2):449. doi:10.3390/ijms20020449
21. Kyriakides TR, Raj A, Tseng TH, et al. Biocompatibility of nanomaterials and their immunological properties. Biomed Mater. 2021;16(4). doi:10.1088/1748-605X/abe5fa
22. Bahadur S, Pathak K. Physicochemical and physiological considerations for efficient nose-to-brain targeting. Expert Opin Drug Deliv. 2012;9(1):19-31. doi:10.1517/17425247.2012.636801
23. Ait-Touchente Z, Zine N, Jaffrezic-Renault N, et al. Exploring the versatility of microemulsions in cutaneous drug delivery: Opportunities and challenges. Nanomaterials (Basel). 2023;13(10):1688. doi:10.3390/nano13101688
24. Ustündağ Okur N, Yavaşoğlu A, Karasulu HY. Preparation and evaluation of microemulsion formulations of naproxen for dermal delivery. Chem Pharm Bull (Tokyo). 2014;62(2):135-143. doi:10.1248/cpb.c13-00051
25. Froelich A, Osmałek T, Jadach B, et al. Microemulsion-based media in nose-to-brain drug delivery. Pharmaceutics. 2021;13(2):201. doi:10.3390/pharmaceutics13020201
26. Qing Y, Cheng L, Li R, et al. Potential antibacterial mechanism of silver nanoparticles and the optimization of orthopedic implants by advanced modification technologies. Int J Nanomedicine. 2018;13:3311-3327. doi:10.2147/IJN.S165125
27. Wang L, Hu C, Shao L. The antimicrobial activity of nanoparticles: Present situation and prospects for the future. Int J Nanomedicine. 2017;12:1227-1249. doi:10.2147/IJN.S121956
28. Xu L, Wang YY, Huang J, et al. Silver nanoparticles: Synthesis, medical applications and biosafety. Theranostics. 2020;10(20):8996-9031. doi:10.7150/thno.45413
29. Kamer AMA, El Maghraby GM, Shafik MM, et al. Silver nanoparticle with potential antimicrobial and antibiofilm efficiency against multiple drug resistant, extensive drug resistant Pseudomonas aeruginosa clinical isolates. BMC Microbiol. 2024;24(1):277. doi:10.1186/s12866-024-03397-z