{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:38:51Z","timestamp":1792791531388,"version":"4.5.0"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Introduction:<\/jats:bold>\n                    Vaginal candidiasis remains a recurrent fungal infection affecting millions of women worldwide, necessitating innovative local delivery systems to overcome poor drug solubility and mucosal barriers. This study introduces Dual-Functional Hybrid Cationic PEGylated Proniosomes (DHCPP) as a smart nano-platform designed to boost the vaginal delivery of Fenticonazole Nitrate (FTN).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    DHCPP systems were fabricated via the coacervation phase separation method and optimized using a full 2\n                    <jats:sup>3<\/jats:sup>\n                    factorial design, achieving a high desirability value of 0.931. The optimized DHCPP exhibited an encapsulation efficiency of 91.61%, particle size of 238.85 nm, and zeta potential of +58.85 mV, ensuring colloidal stability and efficient mucosal interaction.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    <jats:italic>In-vitro<\/jats:italic>\n                    characterization using TEM and FTIR verified the formation of uniform spherical vesicles and successful FTN encapsulation without chemical incompatibility. Mucoadhesion testing revealed superior adhesive strength, indicating prolonged vaginal residence, while drug release followed a diffusion-controlled pattern. The optimized DHCPP was incorporated into a carbopol-based gel exhibiting pseudo-plastic rheology and pH compatibility with the vaginal environment. Multi-scale\n                    <jats:italic>ex vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    evaluations revealed a 2.36-fold permeation enhancement compared to FTN gel, consistent with deeper mucosal penetration observed via confocal microscopy. The microbiological assessment indicated a pronounced reduction in MIC and MFC values and a remarkable improvement in biofilm inhibitory effect, highlighting enhanced antifungal efficacy. Histopathological examination verified the mucosal safety of the optimized gel.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    The developed DHCPP represents an innovative, multifunctional, and biocompatible delivery system offering enhanced vaginal permeation, prolonged retention, and potent antifungal activity for the effective management of vaginal candidiasis.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2025.1746918","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T06:45:06Z","timestamp":1769582706000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["Innovative dual-functional hybrid cationic PEGylated proniosomes as a smart nano-platform for Boosted vaginal delivery: multi-level in-vitro, ex-vivo, microbiological, and in-vivo studies"],"prefix":"10.3389","volume":"16","author":[{"given":"Sadek","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Saher","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University","place":["Cairo, Egypt"]},{"name":"Department of Laboratory Medicine, Karolinska Institute","place":["Stockholm, Sweden"]},{"name":"Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Attia","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdurrahman M.","family":"Fahmy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University","place":["Cairo, Egypt"]},{"name":"School of Life and Medical Sciences, University of Hertfordshire Hosted By Global Academic Foundation","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Islam M.","family":"Adel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.ijpharm.2015.03.020","article-title":"Design and optimization of topical methotrexate loaded niosomes for enhanced management of psoriasis: application of box-behnken design, in-vitro evaluation and in-vivo skin deposition study","volume":"485","author":"Abdelbary","year":"2015","journal-title":"Int. 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