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Reducing drug particles to the micron or nanometer scale can enhance bioavailability. Supercritical fluid technology, as a green drug development strategy, is expected to resolve the challenges of thermal degradation, uneven particle size, and organic solvent residue faced by traditional methods such as milling and crystallization. This paper provides an insight into the application of super-stable homogeneous intermix formulating technology (SHIFT) and super-table pure-nanomedicine formulation technology (SPFT) developed based on supercritical fluids for drug dispersion and micronization. These technologies significantly enhance the solubility and permeability of hydrophobic drugs by controlling the particle size and morphology, and the modified drugs show excellent therapeutic efficacy in the treatment of hepatocellular carcinoma, pathological scarring, and corneal neovascularization, and their performance and efficacy are highlighted when administered through multiple routes of administration. Overall, supercritical fluids have opened a green and efficient pathway for clinical drug development, which is expected to reduce side effects and enhance therapeutic efficacy.<\/jats:p>","DOI":"10.3390\/bioengineering11080788","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T15:45:22Z","timestamp":1722872722000},"page":"788","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Supercritical Fluids: An Innovative Strategy for Drug Development"],"prefix":"10.3390","volume":"11","author":[{"given":"Hui","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoliu","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yisheng","family":"Peng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2613-7286","authenticated-orcid":false,"given":"Gang","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4251-0645","authenticated-orcid":false,"given":"Hongwei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Zhuhai UM Science & Technology Research Institute, University of Macau, Macau SAR 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nnano.2017.142","article-title":"The sounds of nanotechnology","volume":"12","author":"Campbell","year":"2017","journal-title":"Nat. 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