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Perphenazine (PPZ), as a typical antipsychotic medical substance, has the same effectiveness compared to atypical antipsychotic medications for the treatment of schizophrenia. Despite the lipophilic essence, PPZ encounters limited bioavailability caused by the first\u2010pass metabolism following oral administration. In the present study, PPZ\u2010containing solid lipid nanoparticles (PPZ\u2010SLNs) were prepared and optimized based on different factors, including lipid and surfactant amount, to develop appropriate and safe novel oral dosage forms of PPZ. <jats:italic>Methods<\/jats:italic>. The solvent emulsification\u2010evaporation method was utilized to form SLNs by using soybean lecithin, glycerol monostearate (GMS), and Tween 80. Statistical optimization was done by the Box\u2010Behnken design method to achieve formulation with optimized particle size, entrapment efficiency, and zeta potential. Also, transmission electron microscopy, <jats:italic>in vitro<\/jats:italic> release behavior, differential scanning calorimetry (DSC), and powder X\u2010ray diffractometry (P\u2010XRD) studies and cytotoxicity studies were assessed. <jats:italic>Results<\/jats:italic>. Optimization exhibited the significant effect of various excipients on SLN characteristics. Our finding indicated that the mean particle size, zeta potential, and entrapment efficiency of optimized PPZ\u2010SLN were, respectively, 104 \u00b1 3.92\u2009nm, \u221228 \u00b1 2.28\u2009mV, and 83<jats:italic>%<\/jats:italic> \u00b1 1.29. Drug release of PPZ\u2010SLN was observed to be greater than 90% for 48\u2009h that emphasized a sustained\u2010release pattern. The DSC and P\u2010XRD studies revealed the amorphous state of PPZ\u2010SLN. FTIR spectra showed no incompatibility between the drug and the lipid. Performing cytotoxicity studies indicated no significant cytotoxicity on HT\u201029 cell culture. <jats:italic>Conclusion<\/jats:italic>. Our study suggests that PPZ\u2010SLNs can make a promising vehicle for a suitable therapy of schizophrenia for the oral drug delivery system.<\/jats:p>","DOI":"10.1155\/2021\/6619195","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:53:55Z","timestamp":1619657635000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Development of Perphenazine\u2010Loaded Solid Lipid Nanoparticles: Statistical Optimization and Cytotoxicity Studies"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7709-715X","authenticated-orcid":false,"given":"Parisa Abbasi","family":"Farsani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7056-2020","authenticated-orcid":false,"given":"Reza","family":"Mahjub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3957-2781","authenticated-orcid":false,"given":"Mojdeh","family":"Mohammadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8654-6148","authenticated-orcid":false,"given":"Seyed Sajad","family":"Oliaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1395-1457","authenticated-orcid":false,"given":"Mohammad Mehdi","family":"Mahboobian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,28]]},"reference":[{"key":"e_1_2_8_1_2","volume-title":"Essentials of Schizophrenia","author":"Lieberman J. 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