{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T11:21:29Z","timestamp":1772104889415,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education, Research, and Innovation (MoHERI), Oman","award":["BFP\/RGP\/HSS\/22\/220"],"award-info":[{"award-number":["BFP\/RGP\/HSS\/22\/220"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Poor oral bioavailability and limited intestinal permeation restrict the clinical translation of phytochemicals for colorectal cancer (CRC) therapy. The present preliminary study explored the development of a nanoparticle-based combinatorial formulation of resveratrol (Resv), acetyl-11-keto-\u03b2-boswellic acid (AKBA), and quercetin (Quer), to improve intestinal permeation and anti-cancer efficacy. Methods: A triple phytochemical nano formulation (designated as 3X) was developed and evaluated for morphology, particle size, zeta potential, encapsulation efficiency, and in vitro pharmaceutical characteristics. Safety was evaluated using in vitro cytotoxicity assays, while anticancer efficacy and apoptotic potential were preliminarily evaluated in Caco-2 CRC cell lines. Gene expression analysis was performed to examine the modulation of inflammation and cancer-related markers. Results: The 3X formulation exhibited a particle size of 198.5 nm with a polydispersity index of 0.492 and a zeta potential of \u221232.7, indicating good nanoscale stability. The encapsulation efficiencies were 90% for AKBA, 80% for Resv, and 75% for Quer. In vitro permeation studies demonstrated a controlled release mechanism. The formulation showed minimal hemolysis (3%) and had acceptable in vitro safety. The IC50 of the formulation was found to be 365 \u00b5g in the cytotoxicity assay. Treatment with the 3X nanoformulation significantly modulated anti-inflammatory and cancer-related gene expression in Caco2 cells, evidenced by downregulation of TGF\u03b2 (Transforming Growth Factor-beta) and COX-2 (cyclooxygenase-2), and upregulation of TNF\u03b1 (Tumor necrosis factor-alpha) and nitric oxide (NO) and reduced IL-1\u03b2 (Interleukins-1 beta) expression compared with control cells. Conclusions: The findings demonstrate that the developed 3X nano formulation exhibits favorable permeation characteristics and exerts anticancer activity against CRC. Based on preliminary findings, the formulation represents a promising phytochemical-based combination strategy for CRC, warranting further in vivo studies to validate its efficacy and elucidate the underlying molecular mechanisms.<\/jats:p>","DOI":"10.3390\/pharmaceutics18020277","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T16:22:55Z","timestamp":1771863775000},"page":"277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Formulation, Characterization, and In Vitro Biological Evaluation of a Triple-Phytochemical Nano Delivery System for Colon Cancer Therapy\u2014A Preliminary Feasibility Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2689-4079","authenticated-orcid":false,"given":"Dhanalekshmi Unnikrishnan","family":"Meenakshi","sequence":"first","affiliation":[{"name":"College of Pharmacy, National University of Science and Technology, Muscat PC 130, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-4622","authenticated-orcid":false,"given":"Gurpreet Kaur","family":"Narde","sequence":"additional","affiliation":[{"name":"College of Pharmacy, National University of Science and Technology, Muscat PC 130, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0729-3403","authenticated-orcid":false,"given":"Shah Alam","family":"Khan","sequence":"additional","affiliation":[{"name":"College of Pharmacy, National University of Science and Technology, Muscat PC 130, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9295-2521","authenticated-orcid":false,"given":"Alka","family":"Ahuja","sequence":"additional","affiliation":[{"name":"College of Pharmacy, National University of Science and Technology, Muscat PC 130, Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.32604\/or.2023.042228","article-title":"Recent Updates on Nano-Phyto-Formulations-Based Therapeutic Intervention for Cancer Treatment","volume":"32","author":"Wahi","year":"2023","journal-title":"Oncol. 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