{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:06:21Z","timestamp":1788944781344,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China (NSFC) General Program","award":["82574596"],"award-info":[{"award-number":["82574596"]}]},{"name":"Liaoning Provincial Doctoral Scientific Research Start-up Foundation Project","award":["2024-BS-328"],"award-info":[{"award-number":["2024-BS-328"]}]},{"DOI":"10.13039\/501100012131","name":"Department of Science and Technology of Liaoning Province","doi-asserted-by":"publisher","award":["2026-BS-0646"],"award-info":[{"award-number":["2026-BS-0646"]}],"id":[{"id":"10.13039\/501100012131","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2026-BS-0646"],"award-info":[{"award-number":["2026-BS-0646"]}],"id":[{"id":"https:\/\/ror.org\/02f09cx53","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: The oral application of adenovirus is hindered by its poor in vitro storage stability and rapid degradation by gastric acid. To address this, a biomimetic oral adenovirus delivery system (CSP-AdV@LYO) was constructed based on three key properties of natural chrysanthemum sporopollenin (CSP): chemical inertness, intelligent \u201cacid-shrinking\/alkali-swelling\u201d responsiveness, and mucosal adhesion via its spike structures, aiming to enhance oral stability and delivery efficiency. Methods: First, low-allergenic chrysanthemum pollen was screened using proteomics and a zebrafish allergy model. High-purity sporopollenin (SPO) was then extracted via an acidolysis method, followed by systematic characterization of its morphology, particle size, zeta potential, contact angle, and reversible acid-shrinking\/alkali-swelling behavior. Subsequently, a CSP-AdV@LYO formulation was prepared by optimizing a cryoprotectant formulation (sucrose:gelatin = 1:1) and a vacuum loading process. Its protective and release properties were evaluated in vitro using simulated gastric and intestinal fluids, and its long-term stability was assessed. Further in vivo studies in mice assessed its intestinal colonization efficiency. The adhesion mechanism of the sporopollenin spike structures was investigated through mucosal retention experiments. Results: Mucosal retention experiments confirmed that the spike structures on the sporopollenin surface enhanced retention by approximately 3-fold through mechanical interlocking compared to smooth particles. In long-term stability tests, the viral genome copy number retention rate was improved more than 10-fold compared to the virus stock solution. The system enabled a steady and controlled release of the virus in simulated intestinal fluid, with the released virus maintaining its infectivity. In vivo studies demonstrated that CSP-AdV@LYO promoted efficient intestinal colonization and reduced acute mortality from 75% (AdV@LYO group) to 25%. Conclusions: By leveraging the unique physicochemical properties of chrysanthemum sporopollenin, this study successfully developed a biomimetic oral delivery system for live adenovirus that provides gastric acid protection, intelligent pH-responsive release, and mucosal adhesion. This system significantly enhances the oral stability and intestinal delivery efficiency of adenovirus while reducing systemic exposure risks. It offers a novel biomimetic strategy for the oral delivery of adenovirus and other biological macromolecules.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091107","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:35:29Z","timestamp":1788359729000},"page":"1107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of an Oral Delivery System for Live Adenovirus Based on Bionic Chrysanthemum Sporopollenin Exine Armor"],"prefix":"10.3390","volume":"18","author":[{"given":"Jun","family":"Liu","sequence":"first","affiliation":[{"name":"Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Heping District, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Shuang","family":"Liu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Jianxiong","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Heping District, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Zifang","family":"Ding","sequence":"additional","affiliation":[{"name":"Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Heping District, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Xiaodan","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Clinical Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Heping District, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Jin","family":"Sun","sequence":"additional","affiliation":[{"name":"Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Heping District, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Shujun","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Heping District, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5400-6286","authenticated-orcid":false,"given":"Shanhu","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Advanced Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Yuanqing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Heping District, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sallard, E., Zhang, W., Aydin, M., Schr\u00f6er, K., and Ehrhardt, A. 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