{"title":"Isotretinoin-Loaded Topical Lipid Liquid Crystal for the Treatment of Acne: In-Vitro and In-Vivo Evaluations","authors":"Armita Sedighidarijani, Shiva Golmohammadzadeh, Hossein Kamali, Bahman Khameneh, Elham Khodaverdi, Ali Nokhodchi","doi":"10.1208/s12249-025-03106-7","DOIUrl":null,"url":null,"abstract":"<div><p>Effective acne treatment is critical due to its profound impact on physical and psychological well-being. It was shown that severe systemic side effects, including teratogenicity, ovarian reserve reduction, depression, dry skin, hypertriglyceridemia, and intracranial hypertension limited oral isotretinoin usage. Therefore, this study addresses these challenges by developing isotretinoin-loaded lipid liquid crystal (LLC-IT) nanoparticles for topical application, aiming to enhance localized delivery while minimizing systemic exposure. LLC-IT nanoparticles were prepared using a top-down method and evaluated for their physicochemical properties, photostability, cytotoxicity, antimicrobial activity, <i>in-vitro</i> drug release, and <i>in-vivo</i> therapeutic efficacy. A testosterone-induced acne mouse model was used to compare LLC-IT treatment with untreated and commercial isotretinoin gel-treated groups. LLC-IT nanoparticles exhibited a uniform particle size (69.57 ± 0.51 nm), low polydispersity index (0.264 ± 0.01), and stable zeta potential (- 19.3 ± 0.2 mV). High encapsulation efficiency (95% ± 3) and effective loading capacity (1.15% ± 0.13) were achieved. Drug release was diffusion-controlled with minimal UV-induced degradation. Stability assessments over 12 months confirmed consistent properties across varying storage temperatures. LLC-IT displayed significant antibacterial activity and reduced skin irritation in Draize tests compared to commercial gels. <i>In-vivo</i>, LLC-IT reduced inflammation significantly more than untreated or commercial gel-treated groups, indicating enhanced therapeutic efficacy of LLC-IT formulation. The isotretinoin-loaded lipid liquid crystal formulation shows superior stability and efficacy with reduced side effects compared to conventional treatments, offering a more effective and patient-friendly solution, as well as a promising alternative for industrial production in acne management.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03106-7.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"AAPS PharmSciTech","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1208/s12249-025-03106-7","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Effective acne treatment is critical due to its profound impact on physical and psychological well-being. It was shown that severe systemic side effects, including teratogenicity, ovarian reserve reduction, depression, dry skin, hypertriglyceridemia, and intracranial hypertension limited oral isotretinoin usage. Therefore, this study addresses these challenges by developing isotretinoin-loaded lipid liquid crystal (LLC-IT) nanoparticles for topical application, aiming to enhance localized delivery while minimizing systemic exposure. LLC-IT nanoparticles were prepared using a top-down method and evaluated for their physicochemical properties, photostability, cytotoxicity, antimicrobial activity, in-vitro drug release, and in-vivo therapeutic efficacy. A testosterone-induced acne mouse model was used to compare LLC-IT treatment with untreated and commercial isotretinoin gel-treated groups. LLC-IT nanoparticles exhibited a uniform particle size (69.57 ± 0.51 nm), low polydispersity index (0.264 ± 0.01), and stable zeta potential (- 19.3 ± 0.2 mV). High encapsulation efficiency (95% ± 3) and effective loading capacity (1.15% ± 0.13) were achieved. Drug release was diffusion-controlled with minimal UV-induced degradation. Stability assessments over 12 months confirmed consistent properties across varying storage temperatures. LLC-IT displayed significant antibacterial activity and reduced skin irritation in Draize tests compared to commercial gels. In-vivo, LLC-IT reduced inflammation significantly more than untreated or commercial gel-treated groups, indicating enhanced therapeutic efficacy of LLC-IT formulation. The isotretinoin-loaded lipid liquid crystal formulation shows superior stability and efficacy with reduced side effects compared to conventional treatments, offering a more effective and patient-friendly solution, as well as a promising alternative for industrial production in acne management.
期刊介绍：
AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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