A novel lidocaine-chitosan-barium titanate microemulsion gel for prolonged local anesthesia: An in vitro study

Authors

DOI:

https://doi.org/10.2298/ABS240707024Q

Keywords:

lidocaine, chitosan, barium titanate (BaTiO3), microemulsion, local anesthesia

Abstract

Paper description:

  • A new formulation of lidocaine microemulsions containing chitosan and BaTiO3 nanoparticles was developed for delivering lidocaine through the skin to achieve prolonged topical anesthesia.
  • The lidocaine/chitosan/BaTiO3 microemulsion exhibited a nanometer size range of 7-30 nm with a narrow particle size distribution.
  • The inclusion of BaTiO3 nanoparticles achieved over 84% drug release within 24 h, compared to 52% for the lidocaine/chitosan formulation without BaTiO3.
  • At the concentrations tested, the lidocaine-loaded chitosan and lidocaine-loaded chitosan with BaTiO3 microemulsion gel showed a moderate effect on cellular viability, providing a non-toxic environment

Abstract: This study investigated the efficacy of a novel lidocaine-chitosan-barium titanate microemulsion gel for prolonged local anesthesia. The lidocaine microemulsion comprised 5% (w/w) lidocaine, linoleic acid (LA), chitosan, barium titanate (BaTiO3), Cremophor RH40, Tween 20, and water. Dynamic light scattering was utilized to analyze the particle size of the prepared microemulsions. The optimized microemulsion was transformed into a microemulsion gel to extend the duration of the microemulsion when administered to specific areas. Virgin oil was used as an auxiliary oil to increase the microemulsion area, allowing for a reduced amount of surfactant. In vitro analysis was conducted to evaluate the release of lidocaine from the microemulsion. The lidocaine/chitosan/BaTiO3 ranged in size from 7-30 nm, displaying a narrow particle size distribution. The polydispersity index (PDI) value was 0.989. Lidocaine/chitosan with BaTiO3 nanoparticles as a carrier achieved over 84% drug release, whereas the lidocaine/chitosan without the BaTiO3 nanoparticles only reached 52% cumulative release. At the concentrations used, the lidocaine-loaded chitosan and lidocaine-loaded chitosan with BaTiO3 showed a moderate effect on cellular viability. In conclusion, a new formulation of lidocaine microemulsions containing chitosan and BaTiO3 was developed and utilized to deliver lidocaine through the skin to achieve topical anesthesia.

 

Downloads

Download data is not yet available.

References

Carvalho G, Nikkhah G, Samii M. Pain management after post-traumatic brachial plexus lesions. Conservative and surgical therapy possibilities. Der Orthopade. 1997;26(7):621-5. https://doi.org/10.1007/s001320050132

Gordon SM, Mischenko AV, Dionne RA. Long-acting local anesthetics and perioperative pain management. Dent Clin North Am. 2010;54(4):611-20. https://doi.org/10.1016/j.cden.2010.06.002

Markman JD, Philip A. Interventional approaches to pain management. Anesthesiol Clin. 2007;25(4):883-98. https://doi.org/10.1016/j.anclin.2007.07.012

Golzari SE, Soleimanpour H, Mahmoodpoor A, Safari S, Ala A. Lidocaine and pain management in the emergency department: a review article. Anesth Pain Med. 2014;4(1):e15444. https://doi.org/10.5812/aapm.15444

Epstein-Barash H, Shichor I, Kwon AH, Hall S, Lawlor MW, Langer R, Kohane, D. Prolonged duration local anesthesia with minimal toxicity. Proc Natl Acad Sci U S A. 2009;106(17):7125-30. https://doi.org/10.1073/pnas.0900598106

Lehr VT, Taddio A. Topical anesthesia in neonates: clinical practices and practical considerations. Semin Perinatol. 2007;31(5):323-9. https://doi.org/10.1053/j.semperi.2007.07.008

Ogle OE, Mahjoubi G. Local anesthesia: agents, techniques, and complications. Dent Clin North Am. 2012;56(1):133-48. https://doi.org/10.1016/j.cden.2011.08.003

Zink W, Bohl JR, Hacke N, Sinner B, Martin E, Graf BM. The long term myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blocks. Anesth Analg. 2005;101(2):548-54. https://doi.org/10.1213/01.ANE.0000155956.59842.0A

Barletta JF. Clinical and economic burden of opioid use for postsurgical pain: focus on ventilatory impairment and ileus. Pharmacotherapy. 2012;32(9pt2):12S-18S. https://doi.org/10.1002/j.1875-9114.2012.01178.x

Ilfeld BM. Continuous peripheral nerve blocks: a review of the published evidence. Anesth Analg. 2011;113(4):904-25. https://doi.org/10.1213/ANE.0b013e3182285e01

Kerr DR, Kohan L. Local infiltration analgesia: a technique for the control of acute postoperative pain following knee and hip surgery: a case study of 325 patients. Acta Orthop. 2008;79(2):174-83. https://doi.org/10.1080/17453670710014950

Quandt JE. Anesthetic considerations for laser, laparoscopy, and thoracoscopy procedures. Clin Tech Small Anim Pract. 1999;14(1):50-5. https://doi.org/10.1016/S1096-2867(99)80027-9

Culp Jr WC, Culp WC. Practical application of local anesthetics. J Vasc Interv Radiol. 2011;22(2):111-8. https://doi.org/10.1016/j.jvir.2010.10.005

Movafegh A, Razazian M, Hajimaohamadi F, Meysamie A. Dexamethasone added to lidocaine prolongs axillary brachial plexus blockade. Anesth Analg. 2006;102(1):263-7. https://doi.org/10.1213/01.ane.0000189055.06729.0a

Alshehri S, Karan R, Ghalayini S, Kahin K, Khan Z, Renn D, Mathew S, Rueping M, Hauser, C. Air-loaded gas vesicle nanoparticles promote cell growth in three-dimensional bioprinted tissue constructs. Int J Bioprint. 2022;8(3):489. https://doi.org/10.18063/ijb.v8i3.489

Sarvari P, Sarvari P. Advances in nanoparticle-based drug delivery in cancer treatment. Glob Transl Med. 2023;2:0394. https://doi.org/https://doi.org/10.36922/gtm.0394

Boedeker BH, Lojeski EW, Kline MD, Haynes DH. Ultra‐Long‐Duration Local Anesthesia Produced by Injection of Lecithin‐Coated Tetracaine Microcrystals. J Clin Pharmacol. 1994;34(6):699-702. https://doi.org/10.1002/j.1552-4604.1994.tb02026.x

Majd MH. Dual-targeting and specific delivery of tamoxifen to cancer cells by modified magnetic nanoparticles using hyaluronic acid and folic acid. Tumor Discov. 2022;1(1):41. https://doi.org/https://doi.org/10.36922/td.v1i1.41

Yusoff MS, Gopinath SC, Uda M, Lakshmipriya T, Yaakub ARW, Anbu P. Conjugation of silver and gold nanoparticles for enhancing antimicrobial activity. INNOSC Theranostics Pharmacol Sci. 2022;4:38-47.

Martínez-Pérez D, Guarch-Pérez C, Purbayanto MAK, Choińska E, Riool M, Zaat SA, Wojciech Ś. 3D-printed dual drug delivery nanoparticle-loaded hydrogels to combat antibiotic-resistant bacteria. Int J Bioprint. 2023;9(3):683. https://doi.org/10.18063/ijb.683

Maulvi FA, Parmar RJ, Desai AR, Desai DM, Shukla MR, Ranch KM, Shah SA, Shah DO. Tailored gatifloxacin Pluronic® F-68-loaded contact lens: addressing the issue of transmittance and swelling. Int J Pharm. 2020;581:119279. https://doi.org/10.1016/j.ijpharm.2020.119279

Beiranvand S, Eatemadi A, Karimi A. New updates pertaining to drug delivery of local anesthetics in particular bupivacaine using lipid nanoparticles. Nanoscale Res Lett. 2016;11:1-10. https://doi.org/10.1186/s11671-016-1520-8

de Paula E, Cereda CM, Fraceto LF, de Araujo DR, Franz-Montan M, Tofoli GR, Ranali J, Volpato MC, Groppo FC. Micro and nanosystems for delivering local anesthetics. Expert Opin Drug Deliv. 2012;9(12):1505-24. https://doi.org/10.1517/17425247.2012.738664

Moller R, Covino BG. Cardiac electrophysiologic properties of bupivacaine and lidocaine compared with those of ropivacaine, a new amide local anesthetic. Anesthesiology. 1990;72(2):322-9. https://doi.org/10.1097/00000542-199002000-00019

Abou-Okeil A, Rehan M, El-Sawy S, El-Bisi M, Ahmed-Farid O, Abdel-Mohdy F. Lidocaine/β-cyclodextrin inclusion complex as drug delivery system. Euro Poly J. 2018;108:304-10.

Pipa-Vallejo A, García-Pola-Vallejo MJ. Local anesthetics in dentistry. Med Oral Patol Oral Cir Bucal. 2004;9(5):438-43.

You P, Yuan R, Chen C. Design and evaluation of lidocaine-and prilocaine-coloaded nanoparticulate drug delivery systems for topical anesthetic analgesic therapy: a comparison between solid lipid nanoparticles and nanostructured lipid carriers. Drug Des Devel Ther. 2017:2743-52. https://doi.org/10.2147/DDDT.S141031

de Paula E, Cereda C, Tofoli GR, Franz-Montan M, Fraceto LF, De Araújo DR. Drug delivery systems for local anesthetics. Recent Pat Drug Deliv Formul. 2010;4(1):23-34. https://doi.org/10.2174/187221110789957228

Morihama ACD, Mierzwa JC. Clay nanoparticles effects on performance and morphology of poly (vinylidene fluoride) membranes. Braz J Chem Eng. 2014;31:79-93. https://doi.org/10.1186/x12781-016-1520-8

Tartaro G, Mateos H, Schirone D, Angelico R, Palazzo G. Microemulsion microstructure (s): A tutorial review. Nanomaterials. 2020;10(9):1657. https://doi.org/10.3390/nano10091657

Xu C, Cao Y, Lei C, Li Z, Kumeria T, Meka AK, Xu J, Liu J, Yan C, Luo L. Polymer–mesoporous silica nanoparticle core–shell nanofibers as a dual-drug-delivery system for guided tissue regeneration. ACS App Nano Mater. 2020;3(2):1457-67. https://doi.org/10.1021/acsanm.9b02298

Jaramillo N, Paucar C, Fernández A, Negrete CG, García C. Microemulsion assisted sol-gel method as approach to load a model anticancer drug inside silica nanoparticles for controlled release applications. Coll Interface Sci Commu. 2018;24:13-7. https://doi.org/10.2147/x123.S141031

Kang D-K, Zhao L-Y, Wang H-L. Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines. Rev Bras Anestesiol. 2016;66:594-602. https://doi.org/10.1016/j.bjan.2016.08.002

Breu A, Scheidhammer I, Kujat R, Graf B, Angele P. Local anesthetic cytotoxicity on human mesenchymal stem cells during chondrogenic differentiation. Knee Surg Sports Traumatol Arthrosc. 2015;23:937-45. https://doi.org/10.1007/s00167-014-3312-y

Wu T, Smith J, Nie H, Wang Z, Erwin PJ, Van Wijnen AJ, Qu W. Cytotoxicity of local anesthetics in mesenchymal stem cells. Am J Phys Med Rehabil. 2018;97(1):50-5. https://doi.org/10.1097/PHM.0000000000000837

Hasan S, Thomas N, Thierry B, Prestidge CA. Controlled and localized nitric oxide precursor delivery from chitosan gels to Staphylococcus aureus biofilms. J Pharm Sci. 2017;106(12):3556-63. https://doi.org/10.1016/j.xphs.2017.08.006

Nath SD, Abueva C, Kim B, Lee BT. Chitosan–hyaluronic acid polyelectrolyte complex scaffold crosslinked with genipin for immobilization and controlled release of BMP-2. Carbohydr Polym. 2015;115:160-9. https://doi.org/10.1016/j.carbpol.2014.08.077

Xiang Z, Xu L, Shan Y, Cui X, Shi B, Xi Y, Ren P, Zheng X, Zhao C, Luo D, Li Z. Tumor microenviroment-responsive self-assembly of barium titanate nanoparticles with enhanced piezoelectric catalysis capabilities for efficient tumor therapy. Bio Mater. 2024;1;33:251-61. https://doi.org/10.1016/j.bioactmat.2023.11.004

Onorato GD, Amaral DL, Oliveira LF, Brandao HD, Munk M. Barium Titanate Nanoparticles Exhibit Cytocompatibility in Cultured Bovine Fibroblasts: A Model for Dermal Exposure. Cur J App Sci Tech. 2024;43(5):1-10. https://doi.org/10.9734/cjast/2024/v43i54372

Downloads

Published

2024-10-25

How to Cite

1.
Qiao X, Li L. A novel lidocaine-chitosan-barium titanate microemulsion gel for prolonged local anesthesia: An in vitro study. Arch Biol Sci [Internet]. 2024Oct.25 [cited 2024Dec.22];76(3):325-33. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/10036

Issue

Vol. 76 No. 3 (2024)

Section

Articles

License

Copyright (c) 2024 Xiaoru Qiao, Ling Li

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.