Poloxamers (P184, P188, and P407) have been investigated as the carrier system for eugenol or thymol. A synergic effect of mixed Poloxamers was proved by enhanced micellar parameters, with a lower critical micelle concentration (about 0.06 mM) and the highest surface adsorption of 9 × 10-7 mol m-2 for P188/P407. Dynamic light scattering revealed a decrease in micellar size after loading with biomolecules. Three mathematical models were applied to study the release kinetics, of which Korsmeyer-Peppas was the best fitted model. Higher relative release was observed for Poloxamer/eugenol samples, up to a value of 0.8. Poloxamer micelles with thymol were highly influential in bacterial reduction. Single P407/eugenol micelles proved to be bacteriostatic for up to 6 h for S. aureus or up to 48 h for E. coli. Mixed micelles were confirmed to have prolonged bacteriostatic activity for up to 72 h against both bacteria. This trend was also proven by the modified Gompertz model. An optimized P188/P407/eugenol micelle was successfully used as a model system for release study with a particle size of less than 30 nm and high encapsulation efficiency surpassing 90%. The developed mixed micelles were proved to have antibiofilm activity, and thus they provide an innovative approach for controlled release with potential in topical applications.

Department of Environmental Protection Engineering Faculty of Technology Tomas Bata University in Zlin Vavreckova 275 760 01 Zlin Czech Republic

Department of Fat Surfactant and Cosmetics Technology Faculty of Technology Tomas Bata University in Zlin Vavreckova 275 760 01 Zlin Czech Republic

See more in PubMed

Zhang Y.; Cai P.; Cheng G.; Zhang Y. A Brief Review Of Phenolic Compounds Identified From Plants: Their Extraction, Analysis, And Biological Activity. Natural Product Communications 2022, 17.10.1177/1934578X211069721. DOI

Ataei M.; Maghsoudi A. S.; Hassani S.. Eugenol. In Encyclopedia of Toxicology; Elsevier, 2024; pp 513–517.

Escobar A.; Pérez M.; Romanelli G.; Blustein G. Thymol bioactivity: A review focusing on practical applications. Arabian J. Chem. 2020, 13 (12), 9243–9269. 10.1016/j.arabjc.2020.11.009. DOI

Nagoor Meeran M. F.; Javed H.; Al Taee H.; Azimullah S.; Ojha S. K. Pharmacological Properties And Molecular Mechanisms Of Thymol: Prospects For Its Therapeutic Potential And Pharmaceutical Development. Frontiers in Pharmacology 2017, 8, 1–34. 10.3389/fphar.2017.00380. PubMed DOI PMC

Tima S.; Anuchapreeda S.; Ampasavate C.; Berkland C.; Okonogi S. Stable curcumin-loaded polymeric micellar formulation for enhancing cellular uptake and cytotoxicity to FLT3 overexpressing EoL-1 leukemic cells. Eur. J. Pharm. Biopharm. 2017, 114, 57–68. 10.1016/j.ejpb.2016.12.032. PubMed DOI

Sedlarikova J.; Janalikova M.; Peer P.; Pavlatkova L.; Minarik A.; Pleva P. Zein-Based Films Containing Monolaurin/Eugenol or Essential Oils with Potential for Bioactive Packaging Application. Int. J. Mol. Sci. 2022, 23 (1), 384.10.3390/ijms23010384. PubMed DOI PMC

Vashi K.; Pathak Y. Y.. Challenges In Targeting To Brain And Brain Tumors. In Nanocarriers for Drug-Targeting Brain Tumors; Elsevier, 2022; pp 51–68.

Das A. K.; Nanda P. K.; Bandyopadhyay S.; Banerjee R.; Biswas S.; McClements D. J. Application Of Nanoemulsion-Based Approaches For Improving The Quality And Safety Of Muscle Foods: A Comprehensive Review. Comprehensive Reviews in Food Science and Food Safety 2020, 19 (5), 2677–2700. 10.1111/1541-4337.12604. PubMed DOI

Klojdová I.; Milota T.; Smetanová J.; Stathopoulos C. Encapsulation: A Strategy To Deliver Therapeutics And Bioactive Compounds?. Pharmaceuticals 2023, 16 (3), 362.10.3390/ph16030362. PubMed DOI PMC

Nugraha D. H.; Anggadiredja K.; Rachmawati H. Mini-Review Of Poloxamer As A Biocompatible Polymer. For Advanced Drug Delivery. Braz. J. Pharm. Sci. 2022, 58, e2112510.1590/s2175-97902022e21125. DOI

Cai X.; Zhai J.; Tran N.; Mulet X.; Drummond C. J.. Lipid Nanoparticle Steric Stabilization Roadmap. In Advances in Biomembranes and Lipid Self-Assembly; Elsevier, 2022; pp 41–75.

Di Spirito N. A.; Grizzuti N.; Lutz-Bueno V.; Urciuoli G.; Auriemma F.; Pasquino R. Pluronic F68 Micelles As Carriers For An Anti-Inflammatory Drug: A Rheological And Scattering Investigation. Langmuir 2024, 40, 1544–1554. 10.1021/acs.langmuir.3c03682. PubMed DOI PMC

Martins J.; Lucredi N.; Oliveira M.; Oliveira A.; Godoy M.; Sá-Nakanishi A.; Bracht L.; Cesar G.; Gonçalves R.; Vicentini V.; Caetano W.; Godoy V.; Bracht A.; Comar J. Poloxamers-based nanomicelles as delivery vehicles of hypericin for hepatic photodynamic therapy. Journal of Drug Delivery Science and Technology 2023, 79, 10404310.1016/j.jddst.2022.104043. DOI

Saffarionpour S. One-step preparation of double emulsions stabilized with amphiphilic and stimuli-responsive block copolymers and nanoparticles for nutraceuticals and drug delivery. J. Colloid Interface Sci. Open 2021, 3, 10002010.1016/j.jciso.2021.100020. DOI

Pleva P.; Bartošová L.; Máčalová D.; Zálešáková L.; Sedlaříková J.; Janalíková M. Biofilm Formation Reduction by Eugenol and Thymol on Biodegradable Food Packaging Material. Foods 2022, 11 (1), 2.10.3390/foods11010002. PubMed DOI PMC

Riess G. Micellization of block copolymers. Prog. Polym. Sci. 2003, 28 (7), 1107–1170. 10.1016/S0079-6700(03)00015-7. DOI

Ćirin D.; Krstonošić V.; Poša M. Properties of poloxamer 407 and polysorbate mixed micelles: Influence of polysorbate hydrophobic chain. Journal of Industrial and Engineering Chemistry 2017, 47, 194–201. 10.1016/j.jiec.2016.11.032. DOI

Darpentigny C.; Marcoux P.; Menneteau M.; Michel B.; Ricoul F.; Jean B.; Bras J.; Nonglaton G. Antimicrobial Cellulose Nanofibril Porous Materials Obtained by Supercritical Impregnation of Thymol. ACS Appl. Bio Mater. 2020, 3 (5), 2965–2975. 10.1021/acsabm.0c00033. PubMed DOI

Opálková Šišková A.; Pleva P.; Hru°za J.; Frajová J.; Sedlaříková J.; Peer P.; Kleinová A.; Janalíková M. Reuse of Textile Waste to Production of the Fibrous Antibacterial Membrane with Filtration Potential. Nanomaterials 2022, 12 (1), 50.10.3390/nano12010050. PubMed DOI PMC

Molecular probes: LIVE/DEAD BacLight Bacterial Viability Kits. ThermoFisher Scientific. https://www.thermofisher.com/document-connect/document-connect.html?url=https://assets.thermofisher.com/TFS-Assets%2FLSG%2Fmanuals%2Fmp07007.pdf (accessed June 6, 2023).

Bąk A.; Pilarek M.; Podgórska W.; Markowska-Radomska A.; Hubacz R. Surface Properties Ofperfluorodecalin–Containing Liquid/Liquid Systems: The Influence Of Pluronic F-68 Dissolved In The Aqueous Phase. J. Fluorine Chem. 2018, 215, 36–43. 10.1016/j.jfluchem.2018.09.002. DOI

Prasanthan P.; Kishore N. Self-Assemblies Of Pluronic Micelles In Partitioning Of Anticancer Drugs And Effectiveness Of This System Towards Target Protein. RSC Adv. 2021, 11 (36), 22057–22069. 10.1039/D1RA03770F. PubMed DOI PMC

Singla P.; Garg S.; Bhatti R.; Peeters M.; Singh O.; Mahajan R. Solubilization of hydrophobic drugs clozapine and oxcarbazepine in the lower and higher molecular weight pluronic mixed micelles-a physicochemical, In vitro release and In vitro anti-oxidant study. J. Mol. Liq. 2020, 317, 11381610.1016/j.molliq.2020.113816. DOI

Patel D.; Patel D.; Ray D.; Kuperkar K.; Aswal V. K.; Bahadur P. Single And Mixed Pluronics Micelles With Solubilized Hydrophobic Additives: Underscoring The Aqueous Solution Demeanor And Micellar Transition. J. Mol. Liq. 2021, 343, 11762510.1016/j.molliq.2021.117625. DOI

Vivero-Lopez M.; Sparacino C.; Quelle-Regaldie A.; Sánchez L.; Candal E.; Barreiro-Iglesias A.; Huete-Toral F.; Carracedo G.; Otero A.; Concheiro A.; Alvarez-Lorenzo C. Pluronic/casein micelles for ophthalmic delivery of resveratrol: In vitro, ex vivo, and in vivo tests. Int. J. Pharm. 2022, 628, 12228110.1016/j.ijpharm.2022.122281. PubMed DOI

Tănase M. A.; Soare A. C.; Diţu L. M.; Nistor C. L.; Mihaescu C. I.; Gifu I. C.; Petcu C.; Cinteza L. O.. Influence Of The Hydrophobicity Of Pluronic Micelles Encapsulating Curcumin On The Membrane Permeability And Enhancement Of Photoinduced Antibacterial Activity. Pharmaceutics 2022, 14 ( (10), ). DOI: 2137.10.3390/pharmaceutics14102137. PubMed DOI PMC

Kaur J.; Singla P.; Kaur I. Labrasol mediated enhanced solubilization of natural hydrophobic drugs in Pluronic micelles: Physicochemical and in vitro release studies. J. Mol. Liq. 2022, 361, 11959610.1016/j.molliq.2022.119596. DOI

Piombino C.; Lange H.; Sabuzi F.; Galloni P.; Conte V.; Crestini C. Lignosulfonate Microcapsules for Delivery and Controlled Release of Thymol and Derivatives. Molecules 2020, 25 (4), 866.10.3390/molecules25040866. PubMed DOI PMC

Zhu Z.; Min T.; Zhang X.; Wen Y. Microencapsulation of Thymol in Poly(lactide-co-glycolide) (PLGA): Physical and Antibacterial Properties. Materials 2019, 12 (7), 113310.3390/ma12071133. PubMed DOI PMC

Sotoudegan F.; Amini M.; Faizi M.; Aboofazeli R. Nimodipine-Loaded Pluronic Block Copolymer Micelles: Preparation, Characterization, In-vitro and In-vivo Studies. Iran. J. Pharm. Res. 2016, 15 (4), 641–661. 10.22037/ijpr.2016.1922. PubMed DOI PMC

Garg S.; Peeters M.; Mahajan R.; Singla P. Loading of hydrophobic drug silymarin in pluronic and reverse pluronic mixed micelles. J. Drug Delivery Sci. Technol. 2022, 75, 10369910.1016/j.jddst.2022.103699. DOI

Russo J.; Fiegel J.; Brogden N. K. Rheological And Drug Delivery Characteristics Of Poloxamer-Based Diclofenac Sodium Formulations For Chronic Wound Site Analgesia. Pharmaceutics 2020, 12 (12), 121410.3390/pharmaceutics12121214. PubMed DOI PMC

Mod Razif M. R. F.; Chan S. Y.; Widodo R. T.; Chew Y.-L.; Hassan M.; Hisham S. A.; Rahman S. A.; Ming L. C.; Tan C. S.; Lee S.-K.; Liew K. B. Optimization Of A Luteolin-Loaded Tpgs/Poloxamer 407 Nanomicelle: The Effects Of Copolymers, Hydration Temperature And Duration, And Freezing Temperature On Encapsulation Efficiency, Particle Size and Solubility. Cancers 2023, 15 (14), 3741.10.3390/cancers15143741. PubMed DOI PMC

Bruschi M. L.Strategies to Modify the Drug Release from Pharmaceutical Systems; Woodhead Publishing, 2015, ISBN 9780081001127.

Peng R.; Yang Z.; Gao Y.; Nie J.; Sun F. Synthesis and Properties of Cationic Photocurable Polymethylsiloxane/Eugenol-Modified Oxetane Monomers. Ind. Eng. Chem. Res. 2022, 61 (7), 2792–2798. 10.1021/acs.iecr.1c04020. DOI

Rathod N.; Kulawik P.; Ozogul F.; Regenstein J.; Ozogul Y. Biological activity of plant-based carvacrol and thymol and their impact on human health and food quality. Trends in Food Science & Technology 2021, 116, 733–748. 10.1016/j.tifs.2021.08.023. DOI

Zhou W.; Wang Z.; Mo H.; Zhao Y.; Li H.; Zhang H.; Hu L.; Zhou X. Thymol Mediates Bactericidal Activity against Staphylococcus aureus by Targeting an Aldo–Keto Reductase and Consequent Depletion of NADPH. J. Agric. Food Chem. 2019, 67 (30), 8382–8392. 10.1021/acs.jafc.9b03517. PubMed DOI

Ulloa P.; Guarda A.; Valenzuela X.; Rubilar J.; Galotto M. Modeling the release of antimicrobial agents (thymol and carvacrol) from two different encapsulation materials. Food Sci. Biotechnol. 2017, 26 (6), 1763–1772. 10.1007/s10068-017-0226-8. PubMed DOI PMC

Du E.; Gan L.; Li Z.; Wang W.; Liu D.; Guo Y. In vitro antibacterial activity of thymol and carvacrol and their effects on broiler chickens challenged with Clostridium perfringens. J. Anim. Sci. Biotechnol. 2015, 6 (1), 58.10.1186/s40104-015-0055-7. PubMed DOI PMC

Lambert R.; Skandamis P.; Coote P.; Nychas G. A study of the minimum inhibitory concentration and mode of action of oregano essential oil, thymol and carvacrol. J. Appl. Microbiol. 2001, 91 (3), 453–462. 10.1046/j.1365-2672.2001.01428.x. PubMed DOI

Walsh S.; Maillard J.; Russell A.; Catrenich C.; Charbonneau D.; Bartolo R. Activity and mechanisms of action of selected biocidal agents on Gram-positive and -negative bacteria. J. Appl. Microbiol. 2003, 94 (2), 240–247. 10.1046/j.1365-2672.2003.01825.x. PubMed DOI

Wang L.; Zhang Y. Eugenol Nanoemulsion Stabilized with Zein and Sodium Caseinate by Self-Assembly. J. Agric. Food Chem. 2017, 65 (14), 2990–2998. 10.1021/acs.jafc.7b00194. PubMed DOI

An S.; Ban E.; Chung I.; Cho Y.; Kim A. Antimicrobial Activities of Propolis in Poloxamer Based Topical Gels. Pharmaceutics 2021, 13 (12), 2021.10.3390/pharmaceutics13122021. PubMed DOI PMC

Namivandi-Zangeneh R.; Yang Y.; Xu S.; Wong E.; Boyer C. Antibiofilm Platform based on the Combination of Antimicrobial Polymers and Essential Oils. Biomacromolecules 2020, 21 (1), 262–272. 10.1021/acs.biomac.9b01278. PubMed DOI

Garcia-Salinas S.; Gámez E.; Landa G.; Arruebo M.; Irusta S.; Mendoza G. Antimicrobial Wound Dressings against Fluorescent and Methicillin-Sensitive Intracellular Pathogenic Bacteria. ACS Appl. Mater. Interfaces 2020, 12 (46), 51302–51313. 10.1021/acsami.0c17043. PubMed DOI