{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T23:13:07Z","timestamp":1786662787333,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T00:00:00Z","timestamp":1751155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Zagreb","award":["KK.01.1.1.02.0021"],"award-info":[{"award-number":["KK.01.1.1.02.0021"]}]},{"name":"European Regional Development Fund","award":["KK.01.1.1.02.0021"],"award-info":[{"award-number":["KK.01.1.1.02.0021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Thymol, one of the main compounds of thyme essential oil, has shown promising effects in treating various skin disorders owing to its anti-inflammatory, antimicrobial and antioxidative activities. Due to its limited solubility in water, thymol is commonly used in higher concentrations to achieve a suitable therapeutic effect, which can consequently lead to skin irritation. To overcome these limitations, we incorporated thymol into a vesicular phospholipid gel (VPG), a novel semisolid dermal vehicle consisting of highly concentrated dispersion of phospholipid vesicles (liposomes). Methods: Thymol was successfully loaded into two VPGs differing in bilayer fluidity, which were characterized for the physicochemical and rheological properties, storage stability, in vitro release, ex vivo skin permeability, in vitro compatibility with epidermal cells, wound healing potential, and antibacterial activity against skin-relevant bacterial strains. Results: High pressure homogenization method enabled preparation of VPG-liposomes of neutral surface charge in the size range 140\u2013150 nm with polydispersity indexes below 0.5. Both types of VPGs exhibited viscoelastic solid-like structures appropriate for skin administration and ensured skin localization of thymol. Although both types of VPGs enabled prolonged release of thymol, the presence of cholesterol in the VPG increased the rigidity of the corresponding liposomes and further slowed down thymol release. Conclusions: Loading of thymol into VPGs significantly reduced its cytotoxicity toward human keratinocytes in vitro even at very high concentrations, compared to free thymol. Moreover, it facilitated in vitro wound healing activity, proving its potential as a vehicle for herbal-based medicines. However, the antibacterial activity of thymol against Staphylococcus aureus and methicillin-resistant S. aureus was hindered by VPGs, which represents a challenge in their development.<\/jats:p>","DOI":"10.3390\/pharmaceutics17070854","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T06:46:12Z","timestamp":1751438772000},"page":"854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Potentials and Challenges in Development of Vesicular Phospholipid Gel as a Novel Dermal Vehicle for Thymol"],"prefix":"10.3390","volume":"17","author":[{"given":"Sabina","family":"Keser","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"},{"name":"R&D, PLIVA Croatia Ltd., TEVA Group, Prilaz Baruna Filipovi\u0107a 25, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5308-4609","authenticated-orcid":false,"given":"Zora","family":"Rukavina","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marica","family":"Jozi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"},{"name":"Healthcare Facility Pharmacy Slavonski Brod, Vukovarska 10, 35000 Slavonski Brod, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Pavlovi\u0107-Mitrovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda","family":"Vodol\u0161ak","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Kranj\u010dec","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darija","family":"Stupin Polan\u010dec","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0253-4028","authenticated-orcid":false,"given":"Gordana","family":"Maravi\u0107-Vlahovi\u010dek","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmina","family":"Lovri\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1923-6542","authenticated-orcid":false,"given":"Maja","family":"\u0160egvi\u0107 Klari\u0107","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9237-3952","authenticated-orcid":false,"given":"\u017deljka","family":"Vani\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3415","DOI":"10.1002\/ptr.7541","article-title":"A systematic review and meta-analysis of the effect of thymol as an anti-inflammatory and wound healing agent","volume":"36","author":"Sales","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101904","DOI":"10.1016\/j.jddst.2020.101904","article-title":"A mini-review of thymol incorporated materials: Applications in antibacterial wound dressing","volume":"60","author":"Najafloo","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.colsurfb.2018.01.053","article-title":"Development of nanoparticles from natural lipids for topical delivery of thymol: Investigation of its anti-inflammatory properties","volume":"164","author":"Pivetta","year":"2018","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.3892\/ol.2016.4237","article-title":"Regulation of C6 glioma cell migration by thymol","volume":"11","author":"Lee","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jconrel.2016.04.030","article-title":"Chemical penetration enhancers in stratum corneum\u2014Relation between molecular effects and barrier function","volume":"232","author":"Pham","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_6","unstructured":"(2024). Thymol. European Pharmacopeia 11.7, Council of Europe."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102609","DOI":"10.1016\/j.jddst.2021.102609","article-title":"Inclusion complex of thymol and hydroxypropyl-\u03b2-cyclodextrin (HP-\u03b2-CD) in polymeric hydrogel for topical application: Physicochemical characterization, molecular docking, and stability evaluation","volume":"64","author":"Garg","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Folle, C., Marqu\u00e9s, A.M., D\u00edaz-Garrido, N., Espina, M., S\u00e1nchez-L\u00f3pez, E., Badia, J., Baldoma, L., Calpena, A.C., and Garc\u00eda, M.L. (2021). Thymol-loaded PLGA nanoparticles: An efficient approach for acne treatment. J. Nanobiotechnol., 19.","DOI":"10.1186\/s12951-021-01092-z"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Deng, L.L., Taxipalati, M., Que, F., and Zhang, H. (2016). Physical characterization and antioxidant activity of thymol solubilized Tween 80 micelles. Sci. Rep., 6.","DOI":"10.1038\/srep38160"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109382","DOI":"10.1016\/j.lwt.2020.109382","article-title":"Thymol and carvacrol in nanoliposomes: Characterization and a comparison with free counterparts against planktonic and glass-adhered Salmonella","volume":"127","author":"Heckler","year":"2020","journal-title":"LWT"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"G\u00e1mez, E., Elizondo-Castillo, H., Tascon, J., Garc\u00eda-Salinas, S., Navascues, N., Mendoza, G., Arruebo, M., and Irusta, S. (2020). Antibacterial effect of thymol loaded SBA-15 nanorods incorporated in PCL electrospun fibers. Nanomaterials, 10.","DOI":"10.3390\/nano10040616"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"123732","DOI":"10.1016\/j.ijpharm.2023.123732","article-title":"Semi-solid functionalized nanostructured lipid carriers loading thymol for skin disorders","volume":"651","author":"Folle","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4174","DOI":"10.2174\/1381612821666150901095838","article-title":"(Phospho)lipid-based nanosystems for skin administration","volume":"21","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.jconrel.2019.03.003","article-title":"Liposomes for delivery of antioxidants in cosmeceuticals: Challenges and development strategies","volume":"300","author":"Moon","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"559","DOI":"10.2478\/acph-2023-0042","article-title":"Azithromycin-loaded liposomal hydrogel: A step forward for enhanced treatment of MRSA-related skin infections","volume":"73","author":"Rukavina","year":"2023","journal-title":"Acta Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"\u010ca\u010di\u0107, A., Amid\u017ei\u0107 Klari\u0107, D., Keser, S., Radikovi\u0107, M., Rukavina, Z., J\u00f8raholmen, M.W., Uzelac, L., Kralj, M., \u0160kalko-Basnet, N., and \u0160egvi\u0107 Klari\u0107, M. (2023). A novel approach for the treatment of aerobic vaginitis: Azithromycin liposomes-in-chitosan hydrogel. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15051356"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.3109\/03639045.2014.938658","article-title":"Elastic liposomes-in-vehicle formulations destined for skin therapy: The synergy between type of liposomes and vehicle","volume":"41","author":"Palac","year":"2015","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"117939","DOI":"10.1016\/j.carbpol.2021.117939","article-title":"Liposomes-in-chitosan hydrogel boosts potential of chlorhexidine in biofilm eradication in vitro","volume":"262","author":"Hemmingsen","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0009-3084(97)00028-5","article-title":"Morphology of semisolid aqueous phosphatidylcholine dispersions, a freeze fracture electron microscopy study","volume":"87","author":"Brandl","year":"1997","journal-title":"Chem. Phys. Lipids"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/08982100601186490","article-title":"Vesicular phospholipid gels: A technology platform","volume":"17","author":"Brandl","year":"2007","journal-title":"J. Liposome Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1023\/A:1016008306952","article-title":"Morphological and thermal properties of vesicular phospholipid gels studied by DSC, rheometry and electron microscopy","volume":"68","author":"Bender","year":"2002","journal-title":"J. Therm. Anal. Calorim."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1097\/00001813-200209000-00003","article-title":"Pharmacokinetics and antitumor activity of vincristine entrapped in vesicular phospholipid gels","volume":"13","author":"Burger","year":"2002","journal-title":"Anticancer Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0378-5173(03)00069-3","article-title":"5-Fluorouracil in vesicular phospholipid gels for anticancer treatment: Entrapment and release properties","volume":"256","author":"Kaiser","year":"2003","journal-title":"Int. J. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2018.12.030","article-title":"Vesicular phospholipid gels as drug delivery systems for small molecular weight drugs, peptides and proteins: State of the art review","volume":"557","author":"Breitsamer","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"127187","DOI":"10.1016\/j.colsurfa.2021.127187","article-title":"Vesicular phospholipid gels as topical ocular delivery system for treatment of anterior uveitis","volume":"627","author":"Fang","year":"2021","journal-title":"Colloid. Surf. A Physicochem. Eng. Asp."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"124931","DOI":"10.1016\/j.ijpharm.2024.124931","article-title":"Vesicular phospholipid gels: A new strategy to improve topical antimicrobial dermatotherapy","volume":"667","author":"Keser","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_27","unstructured":"(2024). Buffer solutions. European Pharmacopeia 11.7, Council of Europe."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ijpharm.2018.10.024","article-title":"Azithromycin-loaded liposomes for enhanced topical treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections","volume":"553","author":"Rukavina","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5957","DOI":"10.2147\/IJN.S211691","article-title":"Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections","volume":"14","author":"Rukavina","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_30","unstructured":"Bruschi, M.L. (2015). Mathematical models of drug. Strategies to Modify the Drug Release from Pharmaceutical Systems, Woodhead Publishing."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.jconrel.2020.05.047","article-title":"A novel kinetic model to describe the ultra-fast triggered release of thermosensitive liposomal drug delivery systems","volume":"324","author":"Lu","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Weng, J., Tong, H.H.Y., and Chow, S.F. (2020). In vitro release study of the polymeric drug nanoparticles: Development and validation of a novel method. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12080732"},{"key":"ref_33","unstructured":"NCCLS (2007). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute\u2014NCCLS."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.mimet.2010.02.004","article-title":"Evaluation of diffusion and dilution methods to determine the antibacterial activity of plant extracts","volume":"81","author":"Piskernik","year":"2010","journal-title":"J. Microbiol. Methods"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.carbpol.2016.03.074","article-title":"Nanoparticle-mediated interplay of chitosan and melatonin for improved wound epithelialisation","volume":"146","author":"Hafner","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yagublu, V., Karimova, A., Hajibabazadeh, J., Reissfelder, C., Muradov, M., Bellucci, S., and Allahverdiyev, A. (2022). Overview of physicochemical properties of nanoparticles as drug carriers for targeted cancer therapy. J. Funct. Biomater., 13.","DOI":"10.3390\/jfb13040196"},{"key":"ref_37","unstructured":"Tekade, R.K. (2019). Chapter 10\u2014Importance of physicochemical characterization of nanoparticles in pharmaceutical product development. Advances in Pharmaceutical Product Development and Research Basic Fundamentals of Drug Delivery, Academic Press."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3109\/08982104.2013.826242","article-title":"Novel vaginal drug delivery system: Deformable propylene glycol liposomes-in-hydrogel","volume":"24","author":"Hurler","year":"2014","journal-title":"J. Liposome Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jddst.2019.01.028","article-title":"Effects of surface charge and flexibility of liposomes on dermal drug delivery","volume":"50","author":"Ibaraki","year":"2019","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Baldassarre, F., Schiavi, D., Ciarroni, S., Tagliavento, V., De Stradis, A., Vergaro, V., Suranna, G.P., Balestra, G.M., and Ciccarella, G. (2023). Thymol-nanoparticles as effective biocides against the quarantine pathogen Xylella fastidiosa. Nanomaterials, 13.","DOI":"10.3390\/nano13071285"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ijfoodmicro.2017.04.003","article-title":"Antimicrobial activity of free and liposome-encapsulated thymol and carvacrol against Salmonella and Staphylococcus aureus adhered to stainless steel","volume":"252","author":"Engel","year":"2017","journal-title":"Int. J. Food Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e01628-20","DOI":"10.1128\/AAC.01628-20","article-title":"Development and characterization of monoolein-based liposomes of carvacrol, cinnamaldehyde, citral, or thymol with anti-candida activities","volume":"65","author":"Dias","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1111\/1346-8138.14489","article-title":"pH in nature, humans and skin","volume":"45","author":"Proksch","year":"2018","journal-title":"J. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.jid.2024.07.009","article-title":"The skin acid mantle: An update on skin pH","volume":"145","author":"Brooks","year":"2025","journal-title":"J. Investig. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sim, P., Strudwick, X.L., Song, Y., Cowin, A.J., and Garg, S. (2022). Influence of Acidic pH on wound healing in vivo: A novel perspective for wound treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113655"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Luki\u0107, M., Panteli\u0107, I., and Savi\u0107, S.D. (2021). Towards optimal pH of the skin and topical formulations: From the current state of the art to tailored products. Cosmetics, 8.","DOI":"10.3390\/cosmetics8030069"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0009-3084(93)90053-6","article-title":"Chemical stability of liposomes: Implications for their physical stability","volume":"64","author":"Grit","year":"1993","journal-title":"Chem. Phys. Lipids"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ejps.2018.11.014","article-title":"On-line rheological characterization of semi-solid formulations","volume":"128","author":"Qwist","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Beck, R., Guterres, S., and Pohlmann, A. (2011). Rheological behavior of semisolid formulations containing nanostructured systems. Nanocosmetics and Nanomedicines, Springer.","DOI":"10.1007\/978-3-642-19792-5"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sim\u00f5es, A., Miranda, M., Cardoso, C., and Vitorino, F.V.A. (2020). Rheology by design: A regulatory tutorial for analytical method validation. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12090820"},{"key":"ref_51","unstructured":"Barnes, H.A. (2000). A Handbook of Elementary Rheology, University of Wales, Institute of Non-Newtonian Fluid Mechanics."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Najafinobar, N., Mellander, L.J., Kurczy, M.E., Dunevall, J., Angerer, T.B., Fletcher, J.S., and Cans, A.S. (2016). Cholesterol alters the dynamics of release in protein independent cell models for exocytosis. Sci. Rep., 6.","DOI":"10.1038\/srep33702"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1021\/acsbiomaterials.6b00681","article-title":"Biomimetic lipid-based nanosystems for enhanced dermal delivery of drugs and bioactive agents","volume":"3","author":"Kotla","year":"2017","journal-title":"ACS Biomater. Sci Eng."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.jconrel.2009.11.006","article-title":"Vesicular phospholipid gel-based depot formulations for pharmaceutical proteins: Development and in vitro evaluation","volume":"142","author":"Tian","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ejpb.2016.06.013","article-title":"Melatonin-loaded chitosan\/Pluronic\u00ae F127 microspheres as in situ forming hydrogel: An innovative antimicrobial wound dressing","volume":"107","author":"Hafner","year":"2016","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3109\/10717544.2013.843610","article-title":"Comparative topical delivery of antifungal drug croconazole using liposome and micro-emulsion-based gel formulations","volume":"21","author":"Fetih","year":"2014","journal-title":"Drug Deliv."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"European Society of Clinical Microbiology and Infectious Diseases (EUCAST) (2003). Determination of minimum inhibitory concentrations (MICs) of antibacterial agents by broth dilution. Clin. Microbiol. Infect., 9, 9\u201315.","DOI":"10.1046\/j.1469-0691.2003.00790.x"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Bogdanov, A., Janov\u00e1k, L., Vrane\u0161, J., Me\u0161trovi\u0107, T., Ljubin-Sternak, S., Cseh, Z., Endr\u00e9sz, V., Buri\u00e1n, K., Vani\u0107, \u017d., and Virok, D.P. (2022). Liposomal encapsulation increases the efficacy of azithromycin against Chlamydia trachomatis. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010036"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Moghtaderi, M., Bazzazan, S., Sorourian, G., Sorourian, M., Akhavanzanjani, Y., Noorbazargan, H., and Ren, Q. (2023). Encapsulation of thymol in gelatin methacryloyl (gelma)-based nanoniosome enables enhanced antibiofilm activity and wound healing. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061699"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Balko, S., Kerr, E., Buchel, E., Logsetty, S., and Raouf, A. (2023). A robust and standardized approach to quantify wound closure using the scratch assay. Methods Protoc., 6.","DOI":"10.3390\/mps6050087"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/7\/854\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:01:22Z","timestamp":1760032882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/7\/854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,29]]},"references-count":60,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["pharmaceutics17070854"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17070854","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,29]]}}}