Development, Characterization, and Immunomodulatory Evaluation of Carvacrol-loaded Nanoemulsion

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2021 Jul 2

PMID 34202367

Citations 5

Authors

Amanda Gabrielle Barros Dantas

Rafael Limongi de Souza

Anderson Rodrigues de Almeida

Francisco Humberto Xavier Junior

Maira Galdino da Rocha Pitta

Moacyr Jesus Barreto de Melo Rego

Elquio Eleamen Oliveira

Affiliations

Soon will be listed here.

Abstract

Carvacrol (CV) is an essential oil with numerous therapeutic properties, including immunomodulatory activity. However, this effect has not been studied in nanoemulsion systems. The objective of this study was to develop an innovative carvacrol-loaded nanoemulsion (CVNE) for immunomodulatory action. The developed CVNE comprised of 5% / oily phase (medium chain triglycerides + CV), 2% / surfactants (Tween 80/Span 80), and 93% / water, and was produced by ultrasonication. Dynamic light scattering over 90 days was used to characterize CVNE. Cytotoxic activity and quantification of cytokines were evaluated in peripheral blood mononuclear cell (PBMC) culture supernatants. CVNE achieved a drug loading of 4.29 mg/mL, droplet size of 165.70 ± 0.46 nm, polydispersity index of 0.14 ± 0.03, zeta potential of -10.25 ± 0.52 mV, and good stability for 90 days. CVNE showed no cytotoxicity at concentrations up to 200 µM in PBMCs. CV diminished the production of IL-2 in the PBMC supernatant. However, CVNE reduced the levels of the pro-inflammatory cytokines IL-2, IL-17, and IFN-γ at 50 µM. In conclusion, a stable CVNE was produced, which improved the CV immunomodulatory activity in PBMCs.

Citing Articles

Carvacrol in asthma management: a comprehensive review of its therapeutic potential and mechanisms of action.

Neopane D, Kushwaha P Pharmacol Rep. 2025; .

PMID: 40067636 DOI: 10.1007/s43440-025-00709-6.

Natural wax-based edible coatings for preserving postharvest quality of mandarin orange.

Devi L, Mukherjee A, Sharma S, Katiyar V, Dutta J, Kumar S Food Chem X. 2025; 26:102302.

PMID: 40060961 PMC: 11889960. DOI: 10.1016/j.fochx.2025.102302.

Carvacrol Essential Oil as a Neuroprotective Agent: A Review of the Study Designs and Recent Advances.

Tareen F, Catenacci L, Perteghella S, Sorrenti M, Bonferoni M Molecules. 2025; 30(1.

PMID: 39795159 PMC: 11721141. DOI: 10.3390/molecules30010104.

Nanoemulsion Improves the Anti-Inflammatory Effect of Intraperitoneal and Oral Administration of Carvacryl Acetate.

Souza R, Opretzka L, Morais M, Melo C, Oliveira B, de Sousa D Pharmaceuticals (Basel). 2024; 17(1).

PMID: 38276002 PMC: 10821396. DOI: 10.3390/ph17010017.

Antifungal activity against Candida albicans of methyl 3,5-dinitrobenzoate loaded nanoemulsion.

Duarte A, Perez-Castillo Y, Alves D, de Castro R, Souza R, de Sousa D Braz J Microbiol. 2023; 55(1):25-39.

PMID: 38135805 PMC: 10920570. DOI: 10.1007/s42770-023-01214-9.

References

Barkat M, Harshita , Rizwanullah M, Pottoo F, Beg S, Akhter S . Therapeutic Nanoemulsion: Concept to Delivery. Curr Pharm Des. 2020; 26(11):1145-1166. DOI: 10.2174/1381612826666200317140600. View

Agudelo-Cuartas C, Granda-Restrepo D, Sobral P, Hernandez H, Castro W . Characterization of whey protein-based films incorporated with natamycin and nanoemulsion of α-tocopherol. Heliyon. 2020; 6(4):e03809. PMC: 7199006. DOI: 10.1016/j.heliyon.2020.e03809. View

Hu M, Xie F, Zhang S, Qi B, Li Y . Effect of nanoemulsion particle size on the bioavailability and bioactivity of perilla oil in rats. J Food Sci. 2020; 86(1):206-214. DOI: 10.1111/1750-3841.15537. View

Pensado A, Fernandez-Pineiro I, Seijo B, Sanchez A . Anionic nanoparticles based on Span 80 as low-cost, simple and efficient non-viral gene-transfection systems. Int J Pharm. 2014; 476(1-2):23-30. DOI: 10.1016/j.ijpharm.2014.09.032. View

Gholijani N, Amirghofran Z . Effects of thymol and carvacrol on T-helper cell subset cytokines and their main transcription factors in ovalbumin-immunized mice. J Immunotoxicol. 2016; 13(5):729-37. DOI: 10.3109/1547691X.2016.1173134. View

Khazdair M, Boskabady M . A double-blind, randomized, placebo-controlled clinical trial on the effect of carvacrol on serum cytokine levels and pulmonary function tests in sulfur mustard induced lung injury. Cytokine. 2018; 113:311-318. DOI: 10.1016/j.cyto.2018.07.031. View

Calton E, Keane K, Newsholme P, Soares M . The Impact of Vitamin D Levels on Inflammatory Status: A Systematic Review of Immune Cell Studies. PLoS One. 2015; 10(11):e0141770. PMC: 4631349. DOI: 10.1371/journal.pone.0141770. View

de Oliveira Pedrosa Rolim M, de Almeida A, Pitta M, Barreto de Melo Rego M, Quintans-Junior L, Quintans J . Design, synthesis and pharmacological evaluation of CVIB, a codrug of carvacrol and ibuprofen as a novel anti-inflammatory agent. Int Immunopharmacol. 2019; 76:105856. DOI: 10.1016/j.intimp.2019.105856. View

Chang Y, McLandsborough L, McClements D . Physical properties and antimicrobial efficacy of thyme oil nanoemulsions: influence of ripening inhibitors. J Agric Food Chem. 2012; 60(48):12056-63. DOI: 10.1021/jf304045a. View

10.

Khan I, Bhardwaj M, Shukla S, Lee H, Oh M, Bajpai V . Carvacrol encapsulated nanocarrier/ nanoemulsion abrogates angiogenesis by downregulating COX-2, VEGF and CD31 in vitro and in vivo in a lung adenocarcinoma model. Colloids Surf B Biointerfaces. 2019; 181:612-622. DOI: 10.1016/j.colsurfb.2019.06.016. View

11.

Aouf A, Ali H, Al-Khalifa A, Mahmoud K, Farouk A . Influence of Nanoencapsulation Using High-Pressure Homogenization on the Volatile Constituents and Anticancer and Antioxidant Activities of Algerian Coss. et Durieu. Molecules. 2020; 25(20). PMC: 7587522. DOI: 10.3390/molecules25204756. View

12.

Souza A, Abreu F, Diniz L, Grespan R, DeSantana J, Quintans-Junior L . The inclusion complex of carvacrol and β-cyclodextrin reduces acute skeletal muscle inflammation and nociception in rats. Pharmacol Rep. 2018; 70(6):1139-1145. DOI: 10.1016/j.pharep.2018.07.002. View

13.

Wu W, Eskin D, Priyadarshi A, Subroto T, Tzanakis I, Zhai W . New insights into the mechanisms of ultrasonic emulsification in the oil-water system and the role of gas bubbles. Ultrason Sonochem. 2021; 73:105501. PMC: 7933810. DOI: 10.1016/j.ultsonch.2021.105501. View

14.

McClements D . Advances in edible nanoemulsions: Digestion, bioavailability, and potential toxicity. Prog Lipid Res. 2020; 81:101081. DOI: 10.1016/j.plipres.2020.101081. View

15.

Gholijani N, Gharagozloo M, Farjadian S, Amirghofran Z . Modulatory effects of thymol and carvacrol on inflammatory transcription factors in lipopolysaccharide-treated macrophages. J Immunotoxicol. 2015; 13(2):157-64. DOI: 10.3109/1547691X.2015.1029145. View

16.

Carpenter J, Saharan V . Ultrasonic assisted formation and stability of mustard oil in water nanoemulsion: Effect of process parameters and their optimization. Ultrason Sonochem. 2017; 35(Pt A):422-430. DOI: 10.1016/j.ultsonch.2016.10.021. View

17.

Hussein J, El-Banna M, Mahmoud K, Morsy S, Latif Y, Medhat D . The therapeutic effect of nano-encapsulated and nano-emulsion forms of carvacrol on experimental liver fibrosis. Biomed Pharmacother. 2017; 90:880-887. DOI: 10.1016/j.biopha.2017.04.020. View

18.

Xiao Y, Li B, Liu J, Ma X . Carvacrol ameliorates inflammatory response in interleukin 1β-stimulated human chondrocytes. Mol Med Rep. 2017; 17(3):3987-3992. DOI: 10.3892/mmr.2017.8308. View

19.

Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A . Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics. 2018; 10(2). PMC: 6027495. DOI: 10.3390/pharmaceutics10020057. View

20.

Liu S, Song M, Yun W, Lee J, Kim H, Cho J . Effect of carvacrol essential oils on immune response and inflammation-related genes expression in broilers challenged by lipopolysaccharide. Poult Sci. 2018; 98(5):2026-2033. DOI: 10.3382/ps/pey575. View