{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T12:28:11Z","timestamp":1792931291789,"version":"4.5.0"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cinacalcet (CINA), a Biopharmaceutics Classification System (BCS) Class IV drug, exhibits limited oral bioavailability due to poor aqueous solubility and low intestinal permeability. We aimed to mechanistically enhance the oral bioavailability of CINA through the development of advanced hybrid-stabilized nanocrystals (HNCs) prepared through high-speed homogenization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A dual-stabilization strategy was implemented, combining a steric stabilizer (polyvinylpyrrolidone K90 or Pluronic\u00ae F-127) with a dispersing stabilizer (Tween\u00ae 80) to synergistically control nanocrystal formation, surface properties, and colloidal stability. A 2\n                      <jats:sup>1<\/jats:sup>\n                      \u00d7\u00b73\n                      <jats:sup>2<\/jats:sup>\n                      mixed factorial design was developed to investigate the effects of steric stabilizer type (Factor-A), total stabilizer concentration (Factor-B), and dispersing stabilizer contribution (Factor-C) on particle size (PS), poly-dispersity index (PDI), and saturated solubility (SS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Numerical optimization identified an optimal formulation exhibiting a PS of 193.44\u00a0nm, a PDI of 0.34, and an SS of 2.04\u00a0mg\/mL, corresponding to a 1.8-fold increase compared with unprocessed CINA (1.10 \u00b1 0.02\u00a0mg\/mL). Furthermore, the optimized formula exhibited a zeta potential (ZP) of \u221224.25 \u00b1 0.64\u00a0mV, indicating good colloidal stability. Transmission electron microscopy confirmed the formation of discrete, uniformly distributed nanocrystals with well-defined nanoscale morphology. The optimized formulation demonstrated markedly enhanced dissolution behavior in simulated gastric (pH 1.2) and intestinal (pH 6.8) media, alongside satisfactory zeta potential and physical stability.\n                      <jats:italic>In vivo<\/jats:italic>\n                      pharmacokinetic evaluation following oral administration revealed a substantial enhancement in systemic exposure, with 10.36- and 7.76-fold increases in peak plasma concentration (Cmax) and area under the plasma concentration\u2013time curve (AUC), respectively, compared to a conventional CINA suspension.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, these findings highlight hybrid-stabilized nanocrystals as a promising strategy for improving the oral bioavailability of poorly soluble and poorly permeable drugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1904508","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:29:30Z","timestamp":1789014570000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Advanced hybrid-stabilized cinacalcet nanocrystals for enhanced oral bioavailability: formulation and integrated in vitro\/in vivo evaluations"],"prefix":"10.3389","volume":"17","author":[{"given":"Rawan Gamal","family":"Eldin","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, School of Pharmacy, Newgiza University","place":["Giza, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma M.","family":"Mosleh","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmacy, Newgiza University","place":["Giza, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Saher","sequence":"additional","affiliation":[{"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"]},{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadek","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Fatouh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, School of Pharmacy, Newgiza University","place":["Giza, Egypt"]},{"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":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"108528","DOI":"10.1016\/j.jddst.2026.108528","article-title":"Enhanced oral bioavailability of ticagrelor via novel cremosomes: development, characterization, and in-vivo pharmacokinetic evaluation","volume":"123","author":"AbouHussein","year":"2026","journal-title":"J. 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