{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:59:29Z","timestamp":1785488369125,"version":"3.56.0"},"reference-count":20,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HaplnScience"},{"name":"Silexn Technology Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: The pericellular matrix (PCM), a highly hydrated hyaluronan (HA)-rich extracellular structure surrounding keratinocytes, serves as a critical regulator of cellular protection, mechanobiological signaling, and epidermal microenvironmental homeostasis. Increasing evidence suggests that age- and stress-associated degradation of the HA-rich PCM contributes to impaired regenerative capacity and increased cellular vulnerability. Recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) has emerged as a promising PCM-stabilizing biomolecule; however, its therapeutic application remains limited by poor skin permeability resulting from the barrier properties of the stratum corneum and the molecular size constraints governing hydrophilic macromolecule delivery. Methods: In the present study, we developed Soluball\u00ae, a dodecylamine-templated mesoporous silica-based carrier system designed to enhance the transdermal delivery of rhHAPLN1. Results: In vitro analyses demonstrated that rhHAPLN1 effectively preserved both the structural integrity and functional hydrodynamic volume of the PCM against hyaluronidase (HAdase)-induced degradation in HaCaT keratinocytes. Furthermore, rhHAPLN1 exhibited no significant cytotoxicity at concentrations up to 1 \u03bcg\/mL and significantly enhanced keratinocyte proliferation under serum-free conditions. Physicochemical characterization revealed that Soluball\u00ae possessed a relatively uniform particle size distribution (284.6 nm), a high specific surface area (1048 m2\/g), and a mesoporous architecture with an average pore diameter of 3.8 nm, supporting efficient loading of hydrophilic biomolecules. Ex vivo permeation studies using human cadaver skin demonstrated that Soluball\u00ae-encapsulated rhHAPLN1 (H-S powder) significantly enhanced cumulative transdermal permeation compared with free rhHAPLN1 (5.54% vs. 0.88%, respectively). To further evaluate platform versatility, water-soluble Vitamin C was employed as a secondary model cargo. Vita-Soluball\u00ae exhibited markedly enhanced permeation across both Strat-M\u00ae artificial membranes and pig epidermis, achieving cumulative permeation values of 119.12 \u00b1 9.38 \u03bcg\/mL and 150.39 \u00b1 29.20 \u03bcg\/mL, respectively. Conclusions: Collectively, these findings suggest that rhHAPLN1 functions as an effective stabilizer of the HA-rich PCM and that Soluball\u00ae enhances the transdermal delivery of hydrophilic biomolecules. Overall, Soluball\u00ae may represent a promising transdermal delivery platform for hydrophilic biomolecules, although further in vivo validation is warranted.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080947","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:20:18Z","timestamp":1785486018000},"page":"947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced Transdermal Delivery of rhHAPLN1 by Soluball\u00ae Promotes Pericellular Matrix Stability and Keratinocyte Protection"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0339-5076","authenticated-orcid":false,"given":"Kyeong Hyeon","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Regulatory Pharmacy, Graduate School, Chung-Ang University, Seoul 06974, Republic of Korea"},{"name":"HaplnScience Inc., Anyang 14058, Republic of Korea"},{"name":"Silexn Technology Co., Ltd., Busan, 48547, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science and Technology, Kyungsung University, Busan 48434, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Hyuk","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science and Technology, Kyungsung University, Busan 48434, Republic of Korea"},{"name":"Brain Busan 21 Plus Research Group, Kyungsung University, Busan 48434, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Taek","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Regulatory Pharmacy, Graduate School, Chung-Ang University, Seoul 06974, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0388-7303","authenticated-orcid":false,"given":"Dae Kyong","family":"Kim","sequence":"additional","affiliation":[{"name":"HaplnScience Inc., Anyang 14058, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1158\/2159-8290.CD-18-0193","article-title":"Remodeling of the collagen matrix in aging skin promotes melanoma metastasis and affects immune cell motility","volume":"9","author":"Kaur","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bergemann, C., Waldner, A.C., Steffen, E., and Nebe, J.B. 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