Evaluating Antimicrobial Potential of Articaine Derivatives in Oral Infections with CMC

A recent joint study conducted by researchers at Sichuan University and the University of Electronic Science and Technology of China (both located in Chengdu, China) employed cell membrane chromatography (CMC), a biomimetic chromatographic method which merges high-performance liquid chromatography (HPLC) with cell biology and receptor pharmacology, to generate different types of derivatives that help develop new oral local anesthetics. This study, published in the Journal of Oral Microbiology, offers new insight into how to improve postoperative dental care by studying and optimizing the molecular structure of articaine (AT), which is a local anesthetic widely employed in clinical practice (1).

Postoperative infection is one of the most common complications in dental procedures. Although local anesthetics effectively block the generation of action potentials and the conduction of nerve impulses and temporarily hinder sensory conduction in nerve terminals and fibers within a specific body area, they are a risk factor for infection (2). Local anesthesia procedures are inherently invasive and can lead to complications when conducted on the infected oral mucosa or with contaminated needles or anesthetics, which may result in local purulent infections or odontogenic bacteremia (3,4).Local anesthetics are categorized into short-acting, intermediate-acting, and long-acting; for dental outpatient surgeries, which demand rapid onset, moderate duration, and minimal toxicity, dental professionals prefer intermediate-acting amide-type local anesthetics like AT (5).

As postoperative infection is one of the most common complications in dental procedures, the development of new oral local anesthetics offering superior anesthesia, enhanced safety, and antimicrobial properties wouldgreatly increase their clinical value. As the common anesthetic widely employed in clinical practice, AT possesses several notable advantages, including its rapid onset of action and minimal potential for toxicity. It is particularly noted for its antibacterial properties against oral pathogens. However, despite its widespread use, AT demonstrated limited effectiveness in providing prolonged anesthesia, and its antibacterial properties have shown minimal impact in clinical settings.

In their study, the research team focused on optimizing the molecular structure of AT and successfully generated different kinds of AT derivatives, with AT-15 identified as the most promising compound. Then, for AT-15, the researchers evaluated their antibacterial capabilities, explored their antibacterial action mechanisms to understand how AT-15 exerts its antibacterial effects. This endeavor aims to develop innovative local anesthetics for preventing postoperative infections (1).

The AT and its derivatives involved in the study were synthesized by referring to the synthesis route in the previous research results of the research group (6) AT and its derivatives were dissolved in methanol at a concentration of 1 mg/mL. The bacterial cell membrane-fixed phase was packed into a chromatographic column using a high-pressure wet method. The chromatographic column was installed in an ultrahigh-pressure liquid chromatography–mass spectrometry (LC–MS) system, and the column was flushed with a mobile phase (pure water) for 2 h after confirming no leakage (1).

Considering the inherent antimicrobial properties of antibiotic, the researchers employed membrane chromatography to screen the antimicrobial performance of derivatives of AT. CMC assesses dissociation constants and binding characteristics between drugs and membrane receptor components and identifies active ingredients in complex samples, demonstrating value in high-throughput screening for various pharmacological activities, including anti-tumor, anti-cardiovascular, anti-diabetic, anti-allergy, anti-benign prostatic hyperplasia, and osteogenic activities (7,8). Previous studies validated the efficacy of CMC as a high-throughput screening method for antimicrobial peptides derived from Jatropha curcas, a species of flowering plant once considered a potential candidate for future biodiesel production (9–11).

The researchers concluded from their study that AT-15 stood out because of its excellent antimicrobial properties, effective anesthetic effects, and relatively high safety profile. Furthermore, AT-15 showed significant antibacterial activity and selectivity against common bacterial strains and demonstrated efficacy in a rat wound infection model. These beneficial effects are probably because of its ability to disrupt bacterial cell membranes and inhibit DNA gyrase activity. This dual mechanism of action not only enhances its effectiveness as an anesthetic but also contributes to its potential use in preventing and treating infections, making AT-15 a promising candidate for further development in clinical settings (1).

Woman suffering from toothache. © PheelingsMedia - stock.adobe.com

References

1. Tan, Y.; Hao, Y.; Fu, Y. et al. Exploring the Antimicrobial Potential of the Articaine Derivative in Oral Infections. J. Oral Microbiol. 2025, 17 (1), 2502455. DOI: 10.1080/20002297.2025.2502455

2. Lirk, P.; Thiry, J.; Bonnet, M. P. et al. PROSPECT Working Group. Pain Management After Laparoscopic Hysterectomy: Systematic Review of Literature and PROSPECT Recommendations. Reg. Anesth Pain Med. 2019, 44 (4), 425-436. DOI: 10.1136/rapm-2018-100024

3. Jian, P.; Zhuang ,Z. Complications of Oral Local Anesthesia and Their Preventive Treatments. Inter. J. Stomatol. 2012, 39 (2), 141–144. DOI: 10.3969/j.issn.1673-5749.2012.02.001

4. Kaewjiaranai, T.; Srisatjaluk, R. L.; Sakdajeyont, W. et al. The Efficiency of Topical Anesthetics as Antimicrobial Agents: A Review of Use in Dentistry. J. Dent. Anesth. Pain Med. 2018, 18 (4), 223-233. DOI: 10.17245/jdapm.2018.18.4.223

5. Oertel, R.; Rahn, R.; Kirch, W. Clinical Pharmacokinetics of Articaine. Clin. Pharmacokinet. 1997, 33 (6), 417-425. DOI: 10.2165/00003088-199733060-00002

6. Hao, Y.; Wang, H.; Liu, X, et al. Deep Simulated Annealing for the Discovery of Novel Dental Anesthetics with Local Anesthesia and Anti-Inflammatory Properties. Acta Pharm. Sin. B 2024, 14 (7), 3086-3109. DOI: 10.1016/j.apsb.2024.01.019

7. Xu, S.; Jiang, W. Q.; Kuang, Y. M. et al. Research Advances of Cell Membrane Chromatography in Screening Bioactive Components from Traditional Chinese Medicines. Northwest Pharm J. 2018, 33 (2), 274–277.

8. Ma, W.; Wang, C.; Liu, R. et al. Advances in Cell Membrane Chromatography. J. Chromatogr A 2021, 1639, 461916. DOI: 10.1016/j.chroma.2021.461916

9. Xiao, J.; Zhang, H.; Niu, L. et al. Efficient Screening of a Novel Antimicrobial Peptide from Jatropha curcas by Cell Membrane Affinity Chromatography. J. Agric. Food Chem. 2011, 59 (4), 1145-1151. DOI: 10.1021/jf103876b

10. Xiao, J,; Zhang, H. An Escherichia coli Cell Membrane Chromatography-Offline LC-TOF-MS Method for Screening and Identifying Antimicrobial Peptides from Jatropha curcas Meal Protein Isolate Hydrolysates. J. Biomol. Screen. 2012, 17 (6), 752-760. DOI: 10.1177/1087057112442744

11. Jatropha curcas. Wikipedia. https://en.wikipedia.org/wiki/Jatropha_curcas (accessed 2025-05-15)