{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:51:37Z","timestamp":1791615097179,"version":"4.3.4"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Curcumin (CUR) is a natural compound that can be combined with miconazole (MCZ) to improve vulvovaginal candidiasis (VVC) caused by Candida albicans treatment\u2019s efficacy. This study aimed to develop ureasil\u2013polyether (U-PEO) vaginal ovules loaded with CUR and MCZ for the treatment of VVC. Physicochemical characterization was performed by thermogravimetry (TGA), differential thermal analysis (DTA), Fourier transform infrared spectroscopy (FTIR), and in vitro release. Antifungal assays were used to determine minimum inhibitory concentrations (MICs) and synergism between CUR and MCZ, and the activity of U-PEO ovules were performed by microdilution and agar diffusion. TGA results showed high thermal stability of the hybrid ovules. In DTA, the amorphous character of U-PEO and a possible interaction between CUR and MCZ were observed. FTIR showed no chemical incompatibility between the drugs. In vitro release resulted in 80% of CUR and 95% of MCZ released within 144 h. The MICs of CUR and MCZ were 256 and 2.5 \u00b5g\/mL, respectively. After combining the drugs, the MIC of MCZ decreased four-fold to 0.625 \u00b5g\/mL, while that of CUR decreased eight-fold to 32 \u00b5g\/mL. Synergism was confirmed by the fractional inhibitory concentration index (FICI) equal to 0.375. U-PEO alone showed no antifungal activity. U-PEO\/MCZ and U-PEO\/CUR\/MCZ ovules showed the greatest zones of inhibition (\u226518 mm). The results highlight the potential of the ovules to be administered at a lower frequency and at reduced doses compared to available formulations.<\/jats:p>","DOI":"10.3390\/pharmaceutics16030312","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T04:31:23Z","timestamp":1708662683000},"page":"312","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Efficacy of Hybrid Vaginal Ovules for Co-Delivery of Curcumin and Miconazole against Candida albicans"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2610-3668","authenticated-orcid":false,"given":"Brenda Maria Silva","family":"Bezerra","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Postgraduate Program, Center for Biological and Health Sciences, State University of Para\u00edba, Av. Juv\u00eancio Arruda, S\/N, Campina Grande 58429-500, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3598-281X","authenticated-orcid":false,"given":"Sara Efig\u00eania Dantas de Mendon\u00e7a","family":"y Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Postgraduate Program, Center for Biological and Health Sciences, State University of Para\u00edba, Av. Juv\u00eancio Arruda, S\/N, Campina Grande 58429-500, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4593-1816","authenticated-orcid":false,"given":"Jos\u00e9 de Oliveira","family":"Alves-J\u00fanior","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Center for Biological and Health Sciences, State University of Para\u00edba, Av. Juv\u00eancio Arruda, S\/N, Campina Grande 58429-500, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bol\u00edvar Ponciano Goulart de Lima","family":"Damasceno","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Postgraduate Program, Center for Biological and Health Sciences, State University of Para\u00edba, Av. Juv\u00eancio Arruda, S\/N, Campina Grande 58429-500, PB, Brazil"},{"name":"Department of Pharmacy, Center for Biological and Health Sciences, State University of Para\u00edba, Av. Juv\u00eancio Arruda, S\/N, Campina Grande 58429-500, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7247-1598","authenticated-orcid":false,"given":"Jo\u00e3o Augusto","family":"Oshiro-Junior","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Postgraduate Program, Center for Biological and Health Sciences, State University of Para\u00edba, Av. Juv\u00eancio Arruda, S\/N, Campina Grande 58429-500, PB, Brazil"},{"name":"Department of Pharmacy, Center for Biological and Health Sciences, State University of Para\u00edba, Av. Juv\u00eancio Arruda, S\/N, Campina Grande 58429-500, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Czechowicz, P., Nowicka, J., and Go\u015bciniak, G. (2022). Virulence Factors of Candida spp. and Host Immune Response Important in the Pathogenesis of Vulvovaginal Candidiasis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115895"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Willems, H.M.E., Ahmed, S.S., Liu, J., Xu, Z., Peters, B.M., Willems, H., Ahmed, S., Liu, J., Xu, Z., and Peters, B. (2020). Vulvovaginal Candidiasis: A Current Understanding and Burning Questions. J. Fungi, 6.","DOI":"10.3390\/jof6010027"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Yano, J., Sobel, J.D., Nyirjesy, P., Sobel, R., Williams, V.L., Yu, Q., Noverr, M.C., and Fidel, P.L. (2019). Current Patient Perspectives of Vulvovaginal Candidiasis: Incidence, Symptoms, Management and Post-Treatment Outcomes. BMC Women\u2019s Health, 19.","DOI":"10.1186\/s12905-019-0748-8"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1055\/s-0039-3400291","article-title":"Antifungal therapy: New and evolving therapies","volume":"41","author":"Ledoux","year":"2020","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Stenkiewicz-Witeska, J.S., and Ene, I.V. (2023). Azole potentiation in Candida species. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011583"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Czajka, K.M., Venkataraman, K., Brabant-Kirwan, D., Santi, S.A., Verschoor, C., Appanna, V.D., Singh, R., Saunders, D.P., and Tharmalingam, S. (2023). Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic Candida Species. Cells, 12.","DOI":"10.3390\/cells12222655"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1007\/s11046-023-00759-5","article-title":"The Role of Novel Antifungals in the Management of Candidiasis: A Clinical Perspective","volume":"188","author":"Ordaya","year":"2023","journal-title":"Mycopathologia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s12281-020-00369-4","article-title":"Combination Therapy for Invasive Fungal Infections","volume":"14","author":"Livengood","year":"2020","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e01073-23","DOI":"10.1128\/mbio.01073-23","article-title":"Powering up antifungal treatment: Using small molecules to unlock the potential of existing therapies","volume":"14","author":"Shapiro","year":"2023","journal-title":"Mbio"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/jac\/dkn488","article-title":"Curcumin as a Promising Antifungal of Clinical Interest","volume":"63","author":"Martins","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_11","first-page":"570","article-title":"Synergistic Anticandidal Activity of Pure Polyphenol Curcumin in Combination with Azoles and Polyenes Generates Reactive Oxygen Species Leading to Apoptosis","volume":"10","author":"Sharma","year":"2010","journal-title":"FEMS Yeast Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.ejps.2017.12.023","article-title":"Improved vaginal retention and enhanced antifungal activity of miconazole microsponges gel: Formulation development and in vivo therapeutic efficacy in rats","volume":"114","author":"Salah","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Truzzi, F., Tibaldi, C., Zhang, Y., Dinelli, G., and D\u2032 Amen, E. (2021). An overview on dietary polyphenols and their biopharmaceutical classification system (BCS). Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115514"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kanojiya, P.S., Wadetwar, R.N., Atole, P.G., Thakrani, K.C., and Gawande, N.P. (2023). Sustained delivery of statistically optimized transfersomal gel of miconazole nitrate for vaginal candidiasis. J. Dispers. Sci. Technol., 1\u201318.","DOI":"10.1080\/01932691.2023.2289621"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s11095-022-03441-5","article-title":"Advanced Solid Formulations for Vulvovaginal Candidiasis","volume":"40","author":"Conte","year":"2023","journal-title":"Pharm. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Oshiro Junior, J.A., Carvalho, F.C., Soares, C.P., Chorilli, M., and Aparecida Chiavacci, L. (2015). Development of Cutaneous Bioadhesive Ureasil-Polyether Hybrid Films. Int. J. Polym. Sci., 2015.","DOI":"10.1155\/2015\/727324"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Oshiro Junior, J.A., Nasser, N.J., Chiari-Andr\u00e9o, B.G., Cuberes, M.T., and Chiavacci, L.A. (2018). Study of triamcinolone release and mucoadhesive properties of macroporous hybrid films for oral disease treatment. Biomed. Phys. Eng. Express, 4.","DOI":"10.1088\/2057-1976\/aaa84b"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/term.3226","article-title":"In vivo effectiveness of hybrid membranes with osteogenic growth peptide for bone regeneration","volume":"15","author":"Barros","year":"2021","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"805","DOI":"10.4155\/tde-2017-0056","article-title":"Designing and Developing Suppository Formulations for Anti-HIV Drug Delivery","volume":"8","author":"Ham","year":"2017","journal-title":"Ther. Deliv."},{"key":"ref_20","unstructured":"Haas, S., Woerdenbag, H., and Sznitowska, M. (2015). Practical Pharmaceutics, Springer."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Oshiro, J.A., Scardueli, C.R., de Oliveira, G.J.P.L., Marcantonio, R.A.C., and Chiavacci, L.A. (2017). Development of ureasil\u2013polyether membranes for guided bone regeneration. Biomed. Phys. Eng. Express, 3.","DOI":"10.1088\/2057-1976\/aa56a6"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Nicolau Costa, K.M., Sato, M.R., Barbosa, T.L.A., Rodrigues, M.G.F., Medeiros, A.C.D., Damasceno, B.P.G.D.L., and Oshiro-J\u00fanior, J.A. (2021). Curcumin-Loaded Micelles Dispersed in Ureasil-Polyether Materials for a Novel Sustained-Release Formulation. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13050675"},{"key":"ref_23","unstructured":"(2017). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts (Standard No. CLSI M27-Ed4)."},{"key":"ref_24","unstructured":"Lorian, V. (2005). Antibiotics in Laboratory Medicine, Lippincott Williams & Wilkins. [5th ed.]."},{"key":"ref_25","unstructured":"(2018). Method for Antifungal Disk Diffusion Susceptibility Testing for Yeasts (Standard No. CLSI M44-Ed3)."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"114133","DOI":"10.1016\/j.addr.2022.114133","article-title":"Women\u2019s preferences and acceptance for different drug delivery routes and products","volume":"182","author":"Oliveira","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.jsps.2013.07.004","article-title":"Dosage uniformity problems which occur due to technological errors in extemporaneously prepared suppositories in hospitals and pharmacies","volume":"22","author":"Kalmar","year":"2014","journal-title":"Saudi Pharm. J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Domsta, V., Krause, J., Weitschies, W., and Seidlitz, A. (2022). 3D Printing of Paracetamol Suppositories: An Automated Manufacturing Technique for Individualized Therapy. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122676"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.addr.2014.05.012","article-title":"Rectal route in the 21st Century to treat children","volume":"73","author":"Jannin","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.foodchem.2014.01.034","article-title":"Thermal degradation kinetics study of curcumin with nonlinear methods","volume":"155","author":"Chen","year":"2014","journal-title":"Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s10973-011-1784-2","article-title":"Synthesis, spectroscopic, thermal characterization, and antimicrobial activity of miconazole drug and its metal complexes","volume":"109","author":"Mohamed","year":"2012","journal-title":"J. Therm. Anal. Calorim."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"da Silva, C.G., Monteiro, J.R., Oshiro-J\u00fanior, J.A., and Chiavacci, L.A. (2023). Hybrid Membranes of the Ureasil-Polyether Containing Glucose for Future Application in Bone Regeneration. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15051474"},{"key":"ref_33","first-page":"19","article-title":"Thermal behaviour of curcumin","volume":"1","author":"Fugita","year":"2012","journal-title":"Braz. J. Therm. Anal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.ejps.2017.10.002","article-title":"Surface-modified mucoadhesive microgels as a controlled release system for miconazole nitrate to improve localized treatment of vulvovaginal candidiasis","volume":"111","author":"Kenechukwu","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.msec.2017.05.034","article-title":"Formulation and in-vitro efficacy of antifungal mucoadhesive polymeric matrices for the delivery of miconazole nitrate","volume":"79","author":"Tejada","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chen, J., Qin, X., Zhong, S., Chen, S., Su, W., and Liu, Y. (2018). Characterization of curcumin\/cyclodextrin polymer inclusion complex and investigation on its antioxidant and antiproliferative activities. Molecules, 23.","DOI":"10.3390\/molecules23051179"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14293","DOI":"10.3390\/molecules200814293","article-title":"The stability, sustained release and cellular antioxidant activity of curcumin nanoliposomes","volume":"20","author":"Chen","year":"2015","journal-title":"Molecules"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.3109\/03639045.2013.801487","article-title":"Solubility enhancement of miconazole nitrate: Binary and ternary mixture approach","volume":"40","author":"Rai","year":"2014","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Oshiro-Junior, J.A., Lusuardi, A., Beamud, E.M., Chiavacci, L.A., and Cuberes, M.T. (2021). Nanostructural Arrangements and Surface Morphology on Ureasil-Polyether Films Loaded with Dexamethasone Acetate. Nanomaterials, 11.","DOI":"10.3390\/nano11061362"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"37364","DOI":"10.1021\/acsami.8b11149","article-title":"Coupling photoluminescence and ionic conduction properties using the different coordination sites of ureasil\u2013polyether hybrid materials","volume":"10","author":"Palacio","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S89","DOI":"10.1093\/cid\/ciab1055","article-title":"Centers for Disease Control and Prevention\u2019s sexually transmitted diseases infection guidelines","volume":"74","author":"Workowski","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1002\/cben.202300027","article-title":"Kinetic modeling to explain the release of medicine from drug delivery systems","volume":"10","author":"Askarizadeh","year":"2023","journal-title":"ChemBioEng Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"132879","DOI":"10.1016\/j.molstruc.2022.132879","article-title":"Interaction behavior of curcumin encapsulated onto functionalized SBA-15 as an efficient carrier and release in drug delivery","volume":"1260","author":"Atiyah","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Xue, B., Yu, Y., Peng, G., Sun, M., Lv, P., and Li, X. (2022). Amphotericin B and Curcumin Co-Loaded Porous Microparticles as a Sustained Release System against Candida albicans. Molecules, 27.","DOI":"10.3390\/molecules27103079"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"153223","DOI":"10.1016\/j.phymed.2020.153223","article-title":"In vitro and in vivo effects of the combination of myricetin and miconazole nitrate incorporated to thermosensitive hydrogels, on C. albicans biofilms","volume":"71","author":"Mo","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1042\/BSR20090151","article-title":"Antifungal curcumin induces reactive oxygen species and triggers an early apoptosis but prevents hyphae development by targeting the global repressor TUP1 in Candida albicans","volume":"30","author":"Sharma","year":"2010","journal-title":"Biosci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1080\/01480545.2020.1778019","article-title":"Miconazole and terbinafine induced reactive oxygen species accumulation and topical toxicity in human keratinocytes","volume":"45","author":"Lam","year":"2022","journal-title":"Drug Chem. Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1128\/AAC.01497-08","article-title":"Curcumin modulates efflux mediated by yeast ABC multidrug transporters and is synergistic with antifungals","volume":"53","author":"Sharma","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1159\/000371759","article-title":"Miconazole nitrate vaginal suppository 1,200 mg versus oral fluconazole 150 mg in treating severe vulvovaginal candidiasis","volume":"80","author":"Fan","year":"2015","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.4103\/jfmpc.jfmpc_584_19","article-title":"The effect of curcumin-based and clotrimazole vaginal cream in the treatment of vulvovaginal candidiasis","volume":"8","author":"Abouali","year":"2019","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1080\/21505594.2015.1039885","article-title":"Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans","volume":"6","author":"Cui","year":"2015","journal-title":"Virulence"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"111581","DOI":"10.1016\/j.msec.2020.111581","article-title":"Characterization of novel human intragenic antimicrobial peptides, incorporation and release studies from ureasil-polyether hybrid matrix","volume":"119","author":"Mariano","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Gamil, Y., Hamed, M.G., Elsayed, M., Essawy, A., Medhat, S., Zayed, S.O., and Ismail, R.M. (2024). The anti-fungal effect of miconazole and miconazole-loaded chitosan nanoparticles gels in diabetic patients with Oral candidiasis-randomized control clinical trial and microbiological analysis. BMC Oral Health, 24.","DOI":"10.1186\/s12903-024-03952-0"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4103\/pjog.pjog_24_22","article-title":"Comparison of the effect of miconazole and clotrimazole in the treatment of vulvovaginal candidiasis among women seen in a tertiary medical center from 2016 to 2020","volume":"46","author":"Marquez","year":"2022","journal-title":"Philipp. J. Obstet. Gynecol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lee, Y.S., Chen, X., Widiyanto, T.W., Orihara, K., Shibata, H., and Kajiwara, S. (2022). Curcumin affects function of Hsp90 and drug efflux pump of Candida albicans. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.944611"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/3\/312\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:03:41Z","timestamp":1760105021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/3\/312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,23]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["pharmaceutics16030312"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16030312","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,23]]}}}