{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:12:48Z","timestamp":1791947568087,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science, Technology, and Innovation Funding Authority (STIFA\/STDF)","award":["47993"],"award-info":[{"award-number":["47993"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Skin cancer has become a global health issue because of increasing exposure to environmental contaminants and UV radiation. Terbinafine hydrochloride (TRB), a broad-spectrum antifungal medication, has demonstrated notable anti-tumor properties in previous studies; however, its repurposing for skin cancer therapy remains underexplored. Objective: This study reports for the first time, the development of a new delivery system: a nanoemulsion (NE)\u2013foam hybrid system, i.e., \u201cnanoemulfoam\u201d (NEF), designed to enhance the topical TRB delivery to the skin. The study applied this new hybrid system on TRB for managing skin cancer. Method: The TRB-loaded NEF was produced by loading TRB into a liquid NE. then this was incorporated into a liquid foam base and actuated into foam using a non-propellant mechanism. The NE was developed utilizing peppermint oil as the oil phase and Tween-20\/ethanol as the surfactant\/co-surfactant combination (Smix). The formulation underwent optimization using the D-optimal design that enabled the simultaneous evaluation of the impact of oil concentration and Tween 20 concentration in the Smix on the particle size (PS), zeta potential (ZP), and dissolution efficiency percent (DE%). Results: The optimal NE formula displayed a small PS of 186.60 \u00b1 2.84 nm, ZP of \u221213.90 \u00b1 0.99 mV, and DE% of 68.50 \u00b1 1.78% (mean \u00b1 SD, n = 3). After incorporation into the foam system, the produced TRB-loaded NEF demonstrated a 7.43-fold increase in the drug transdermal flux in comparison with plain drug foam (p &lt; 0.05). The TRB-loaded NEF showed no signs of inflammation or irritation when applied to abdominal rabbit skin, indicating its safety. The optimum formula exhibited a statistically significant 10-fold increase in cytotoxicity against A-431 skin cancer cells compared to TRB alone, along with a 1.54-fold increase in apoptosis (p &lt; 0.05). Molecular docking studies targeting CDK2, a key regulator of cell proliferation and a known TRB target, revealed that TRB displayed highly favorable binding scores compared to the reference drug. Conclusions: The TRB-loaded NEF represents a promising nanotechnology-based approach for the topical treatment of skin cancer, supporting further investigation toward clinical translation.<\/jats:p>","DOI":"10.3390\/ph18070972","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Development of a Novel Drug Delivery System \u201cNanoemulfoam\u201d for Topical Delivery of Terbinafine Hydrochloride as a Repurposed Therapy in Skin Cancer: Formulation, Optimization, In Vitro Characterization, Ex Vivo Transdermal Permeability, Cytotoxicity Studies, and In Silico Assessment"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2956-0736","authenticated-orcid":false,"given":"Abeer A.","family":"Musallam","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, Giza 12582, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7717-3925","authenticated-orcid":false,"given":"Reem A.","family":"Aldeeb","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, Giza 12582, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riham M.","family":"Mansour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, Giza 12582, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manar Abd El-karim","family":"Kassem","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, Giza 12582, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa Fayez","family":"Saeed","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, Giza 12582, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud A.","family":"Mahdy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7634-2240","authenticated-orcid":false,"given":"Rana M.","family":"Abdelnaby","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9148-3276","authenticated-orcid":false,"given":"Hanan M.","family":"Elnahas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9415-4267","authenticated-orcid":false,"given":"Tarek M.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Leiter, U., Eigentler, T., and Garbe, C. (2014). Epidemiology of Skin Cancer. Sunlight, Vitamin D and Skin Cancer, Springer.","DOI":"10.1007\/978-1-4939-0437-2_7"},{"key":"ref_2","first-page":"89","article-title":"Overview of skin cancer types and prevalence rates across continents","volume":"3","author":"Roky","year":"2024","journal-title":"Cancer Pathog. Ther. Chin. Med. Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1097\/CM9.0000000000003416","article-title":"Recent global patterns in skin cancer incidence, mortality, and prevalence","volume":"138","author":"Wang","year":"2024","journal-title":"Chin. Med. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1111\/j.1365-4632.2010.04474.x","article-title":"Ultraviolet radiation and skin cancer","volume":"49","author":"Narayanan","year":"2010","journal-title":"Int. J. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"YYounis, M.K., Khalil, I.A., Younis, N.S., Eldeen, R.R.F., Abdelnaby, R.M., Aldeeb, R.A., Taha, A.A., and Hassan, D.H. (2023). Aceclofenac\/Citronellol Oil Nanoemulsion Repurposing Study: Formulation, In Vitro Characterization, and In Silico Evaluation of Their Antiproliferative and Pro-Apoptotic Activity against Melanoma Cell Line. Biomedicines, 11.","DOI":"10.3390\/biomedicines11092531"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Alyami, M.H., Musallam, A.A., Ibrahim, T.M., Mahdy, M.A., Elnahas, H.M., and Aldeeb, R.A. (2023). The Exploitation of pH-Responsive Eudragit-Coated Mesoporous Silica Nanostructures in the Repurposing of Terbinafine Hydrochloride for Targeted Colon Cancer Inhibition: Design Optimization, In Vitro Characterization, and Cytotoxicity Assessment. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15122677"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1080\/10717544.2020.1797237","article-title":"Development, optimization, and evaluation of PEGylated brucine-loaded PLGA nanoparticles","volume":"27","author":"Elsewedy","year":"2020","journal-title":"Drug Deliv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1080\/10717544.2022.2075985","article-title":"Optimization of mirtazapine loaded into mesoporous silica nanostructures via Box-Behnken design: In-vitro characterization and in-vivo assessment","volume":"29","author":"Musallam","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-L\u00f3pez, E., Guerra, M., Dias-Ferreira, J., Lopez-Machado, A., Ettcheto, M., Cano, A., Espina, M., Camins, A., Garcia, M.L., and Souto, E.B. (2019). Current applications of nanoemulsions in cancer therapeutics. Nanomaterials, 9.","DOI":"10.3390\/nano9060821"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Adnan, M., Akhter, M.H., Afzal, O., Altamimi, A.S.A., Ahmad, I., Alossaimi, M.A., Jaremko, M., Emwas, A.-H., Haider, T., and Haider, M.F. (2023). Exploring Nanocarriers as Treatment Modalities for Skin Cancer. Molecules, 28.","DOI":"10.3390\/molecules28155905"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Alhakamy, N.A., and Shadab, M. (2019). Repurposing itraconazole loaded PLGA nanoparticles for improved antitumor efficacy in non-small cell lung cancers. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11120685"},{"key":"ref_12","first-page":"100140","article-title":"Atorvastatin-loaded emulsomes foam as a topical antifungal formulation","volume":"4","author":"Eita","year":"2022","journal-title":"Int. J. Pharm. X"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1080\/10717544.2022.2149898","article-title":"Repurposing of atorvastatin emulsomes as a topical antifungal agent","volume":"29","author":"Eita","year":"2022","journal-title":"Drug Delivery"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1016\/j.bcp.2008.02.005","article-title":"SP1-regulated p27\/Kip1 gene expression is involved in terbinafine-induced human A431 cancer cell differentiation: An in vitro and in vivo study","volume":"75","author":"Huang","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0378-5173(00)00449-X","article-title":"Controlled Release of Terbinafine Hydrochloride from PH Sensitive Poly(Acrylamide\/Maleic Acid) Hydrogels","volume":"203","author":"Uzun","year":"2000","journal-title":"Int. J. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1136\/gutjnl-2021-325851","article-title":"Squalene epoxidase drives cancer cell proliferation and promotes gut dysbiosis to accelerate colorectal carcinogenesis","volume":"71","author":"Li","year":"2022","journal-title":"Gut"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1080\/10837450.2020.1863426","article-title":"Investigation of propellant-free aqueous foams as pharmaceutical carrier systems","volume":"26","author":"Farkas","year":"2021","journal-title":"Pharm. Dev. Technol."},{"key":"ref_18","first-page":"5","article-title":"Foams as carrier systems for pharmaceuticals and cosmetics","volume":"89","author":"Farkas","year":"2019","journal-title":"Acta Pharm. Hung."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.cocis.2019.10.007","article-title":"Foam in pharmaceutical and medical applications","volume":"44","author":"Parsa","year":"2019","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Abdallah, M.H., Abu Lila, A.S., El-Nahas, H.M., and Ibrahim, T.M. (2023). Optimization of Potential Nanoemulgels for Boosting Transdermal Glimepiride Delivery and Upgrading Its Anti-Diabetic Activity. Gels, 9.","DOI":"10.3390\/gels9060494"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.jsps.2021.11.006","article-title":"Intranasal delivery of Clozapine using nanoemulsion-based in-situ gels: An approach for bioavailability enhancement","volume":"29","author":"Abdulla","year":"2021","journal-title":"Saudi Pharm. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1080\/10717544.2022.2039805","article-title":"Olive oil and clove oil-based nanoemulsion for topical delivery of terbinafine hydrochloride: In vitro and ex vivo evaluation","volume":"29","author":"Gul","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s40005-024-00666-x","article-title":"Atorvastatin loaded lecithin-coated zein nanoparticles based thermogel for the intra-articular management of osteoarthritis: In-silico, in-vitro, and in-vivo studies","volume":"54","author":"Elgendy","year":"2024","journal-title":"J. Pharm. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"230","DOI":"10.5530\/ijpi.2021.2.41","article-title":"Formulation, Optimization and in vitro Evaluation of Apremilast Nanoemulgel for Topical Delivery","volume":"11","author":"Mulleria","year":"2021","journal-title":"Int. J. Pharm. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.fjps.2017.07.003","article-title":"Enhanced transdermal permeability of Terbinafine through novel nanoemulgel formulation; Development, in vitro and in vivo characterization","volume":"4","author":"Elmataeeshy","year":"2018","journal-title":"Future J. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"119379","DOI":"10.1016\/j.molliq.2022.119379","article-title":"Influence of tween nature and type on physicochemical properties and stability of spearmint essential oil (Mentha spicata L.) stabilized with basil seed mucilage nanoemulsion","volume":"359","author":"Gorjian","year":"2022","journal-title":"J. Mol. Liq."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Shehata, T.M., Elnahas, H.M., and Elsewedy, H.S. (2022). Development, Characterization and Optimization of the Anti-Inflammatory Influence of Meloxicam Loaded into a Eucalyptus Oil-Based Nanoemulgel. Gels, 8.","DOI":"10.3390\/gels8050262"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1111\/jphp.12115","article-title":"Optimization of self-microemulsifying drug delivery system for telmisartan using Box-Behnken design and desirability function","volume":"65","author":"Cho","year":"2013","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2162159","DOI":"10.1080\/10717544.2022.2162159","article-title":"Syringeable atorvastatin loaded eugenol enriched PEGylated cubosomes in-situ gel for the intra-pocket treatment of periodontitis: Statistical optimization and clinical assessment","volume":"30","author":"Elgendy","year":"2023","journal-title":"Drug Deliv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"15593258221095977","DOI":"10.1177\/15593258221095977","article-title":"Development and Evaluation of pH-Responsive Pluronic F 127 Co-Poly- (Acrylic Acid) Biodegradable Nanogels for Topical Delivery of Terbinafine HCL","volume":"20","author":"Hassan","year":"2022","journal-title":"Dose-Response"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1080\/03639045.2017.1417421","article-title":"Upgrading of dissolution and anti-hypertensive effect of Carvedilol via two combined approaches: Self-emulsification and liquisolid techniques","volume":"44","author":"Ibrahim","year":"2018","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ullah, I., Alhodaib, A., Naz, I., Ahmad, W., Ullah, H., Amin, A., and Nawaz, A. (2023). Fabrication of Novel Omeprazole-Based Chitosan Coated Nanoemulgel Formulation for Potential Anti-Microbia; In Vitro and Ex Vivo Characterizations. Polymers, 15.","DOI":"10.3390\/polym15051298"},{"key":"ref_33","unstructured":"Arzhavitina, A. (2009). Foams as Novel Delivery Vehicle for Topical Application. [Ph.D. Thesis, Christian Albrecht University]."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ejpb.2021.07.012","article-title":"Foams as unique drug delivery systems","volume":"167","author":"Hoc","year":"2021","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.cis.2014.10.001","article-title":"Current applications of foams formed from mixed surfactant-polymer solutions","volume":"222","author":"Bureiko","year":"2015","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2010.04.028","article-title":"Foams for pharmaceutical and cosmetic application","volume":"394","author":"Arzhavitina","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1246\/cl.200058","article-title":"Improving foam stability of ethanol\/water mixture with anionic surfactant and long-chain alcohol","volume":"49","author":"Miyashita","year":"2020","journal-title":"Chem. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/(SICI)1097-0010(199604)70:4<531::AID-JSFA533>3.0.CO;2-3","article-title":"The influence of ethanol on the foaming properties of beer protein fractions: A comparison of rudin and microconductivity methods of foam assessment","volume":"70","author":"Brierley","year":"1996","journal-title":"J. Sci. Food Agric."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1007\/s11743-017-2004-2","article-title":"Experimental Investigation of the Mechanism of Foaming Agent Concentration Affecting Foam Stability","volume":"20","author":"Wang","year":"2017","journal-title":"J. Surfactants Deterg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"461","DOI":"10.2174\/1567201816666190118124439","article-title":"Medicated Foams and Film Forming Dosage Forms as Tools to Improve the Thermodynamic Activity of Drugs to be Administered Through the Skin","volume":"16","author":"Gennari","year":"2019","journal-title":"Curr. Drug Deliv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.ijpharm.2009.09.029","article-title":"The effects of particle properties on nanoparticle drug retention and release in dynamic minoxidil foams","volume":"383","author":"Zhao","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Khan, A.S., Shah, K.U., Al Mohaini, M., Alsalman, A.J., Al Hawaj, M.A., Alhashem, Y.N., Ghazanfar, S., Khan, K.A., Niazi, Z.R., and Farid, A. (2022). Tacrolimus-Loaded Solid Lipid Nanoparticle Gel: Formulation Development and In Vitro Assessment for Topical Applications. Gels, 8.","DOI":"10.3390\/gels8020129"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"104435","DOI":"10.1016\/j.jddst.2023.104435","article-title":"Exploring the therapeutic potential of functional excipient-based nanoemulgel of fluticasone propionate for the management of psoriasis","volume":"84","author":"Jain","year":"2023","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.addr.2012.09.032","article-title":"Penetration enhancers","volume":"64","author":"Williams","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Alhasso, B., Ghori, M.U., and Conway, B.R. (2022). Systematic Review on the Effectiveness of Essential and Carrier Oils as Skin Penetration Enhancers in Pharmaceutical Formulations. Sci. Pharm., 90.","DOI":"10.3390\/scipharm90010014"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ejps.2018.03.030","article-title":"Development of core-shell nanocarrier system for augmenting piperine cytotoxic activity against human brain cancer cell line","volume":"118","author":"Sedeky","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zarif Attalla, K., Hassan, D.H., Teaima, M.H., Yousry, C., El-Nabarawi, M.A., Said, M.A., and Elhabal, S.F. (2025). Enhanced Intranasal Delivery of Atorvastatin via Superparamagnetic Iron-Oxide-Loaded Nanocarriers: Cytotoxicity and Inflammation Evaluation and In Vivo, In Silico, and Network Pharmacology Study for Targeting Glioblastoma Management. Pharmaceuticals, 18.","DOI":"10.3390\/ph18030421"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/mc.20800","article-title":"Sen. Terbinafine inhibits oral squamous cell carcinoma growth through anti-cancer cell proliferation and anti-angiogenesis","volume":"51","author":"Chien","year":"2012","journal-title":"Mol. Carcinog."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.1016\/j.ymthe.2022.06.015","article-title":"Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression","volume":"30","author":"Hu","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5302","DOI":"10.1038\/s41388-021-01934-y","article-title":"Antifungal agent Terbinafine restrains tumor growth in preclinical models of hepatocellular carcinoma via AMPK-mTOR axis","volume":"40","author":"Zhang","year":"2021","journal-title":"Oncogene"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1080\/14756366.2022.2096019","article-title":"Design, synthesis and molecular docking of new fused 1H-pyrroles, pyrrolo[3,2-d]pyrimidines and pyrrolo[3,2-e][1, 4]diazepine derivatives as potent EGFR\/CDK2 inhibitors","volume":"37","author":"Belal","year":"2022","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Phagna, M., Badhwar, R., Singh, M., Alhalmi, A., Khan, R., Noman, O.M., and Alahdab, A. (2023). Development and Characterization of Terbinafine-Loaded Nanoemulgel for Effective Management of Dermatophytosis. Gels, 9.","DOI":"10.3390\/gels9110894"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1007\/s13346-023-01316-9","article-title":"Design of mirtazapine solid dispersion with different carriers\u2019 systems: Optimization, in vitro evaluation, and bioavailability assessment","volume":"13","author":"Aldeeb","year":"2023","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Attia, M.S., Radwan, M.F., Ibrahim, T.S., and Ibrahim, T.M. (2023). Development of Carvedilol-Loaded Albumin-Based Nanoparticles with Factorial Design to Optimize In Vitro and In Vivo Performance. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15051425"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.3109\/10717544.2013.878856","article-title":"A novel drug delivery gel of terbinafine hydrochloride with high penetration for external use","volume":"22","author":"Yang","year":"2015","journal-title":"Drug Deliv."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"S641","DOI":"10.1080\/21691401.2018.1505743","article-title":"Hybrid nanocarrier system for guiding and augmenting simvastatin cytotoxic activity against prostate cancer","volume":"46","author":"Sedki","year":"2018","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_57","first-page":"8551","article-title":"\u03b2-caryophyllene ameliorates hepatic ischemia reperfusion-induced in-jury: The involvement of Keap1\/Nrf2\/HO 1\/NQO 1 and TLR4\/NF-\u03baB\/NLRP3 signaling pathways","volume":"26","author":"Mohamed","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/7\/972\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:20Z","timestamp":1760032820000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/7\/972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":57,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ph18070972"],"URL":"https:\/\/doi.org\/10.3390\/ph18070972","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,27]]}}}