Eman M El-Marakby, Hend Fayez, M A Motaleb, Mai Mansour
{"title":"阿托伐他汀载体立方体:增强乳腺癌靶向性的再利用靶向递送系统。","authors":"Eman M El-Marakby, Hend Fayez, M A Motaleb, Mai Mansour","doi":"10.1080/10837450.2024.2323620","DOIUrl":null,"url":null,"abstract":"<p><p>Cancer ranks as one of the most challenging illnesses to deal with because progressive phenotypic and genotypic alterations in cancer cells result in resistance and recurrence. Thus, the creation of novel medications or alternative therapy approaches is mandatory. Repurposing of old drugs is an attractive approach over the traditional drug discovery process in terms of shorter drug development duration, low-cost, highly efficient and minimum risk of failure. In this study Atorvastatin, a statin drug used to treat abnormal cholesterol levels and prevent cardiovascular disease in people at high risk, was introduced and encapsulated in cubic liquid crystals as anticancer candidate aiming at sustaining its release and achieving better cellular uptake in cancer cells. The cubic liquid crystals were successfully prepared and optimized with an entrapment effieciency of 73.57% ±1.35 and particle size around 200 nm. The selected formulae were effectively doped with radioactive iodine <sup>131</sup>I to enable the noninvasive visualization and trafficking of the new formulae. The <i>in vivo</i> evaluation in solid tumor bearing mice was conducted for comparing<sup>131</sup>I-Atorvastatin solution,<sup>131</sup>I-Atorvastatin loaded cubosome and <sup>131</sup>I-Atorvastatin chitosan coated cubosome. The <i>in vivo</i> biodistribution study revealed that tumor radioactivity uptake of <sup>131</sup>I-Atorvastatin cubosome and chitosan coated cubosome exhibited high accumulation in tumor tissues (target organ) scoring ID%/g of 5.67 ± 0.2 and 5.03 ± 0.1, respectively 1h post injection compared to drug solution which recorded 3.09 ± 0.05% 1h post injection. Concerning the targeting efficiency, the target/non target ratio for <sup>131</sup>I-Atorvastatin chitosan coated cubosome was higher than that of <sup>131</sup>I-Atorvastatin solution and <sup>131</sup>I ATV-loaded cubosome at all time intervals and recorded T/NT ratio of 2.908 2h post injection.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"236-247"},"PeriodicalIF":2.6000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Atorvastatin-loaded cubosome: a repurposed targeted delivery systems for enhanced targeting against breast cancer.\",\"authors\":\"Eman M El-Marakby, Hend Fayez, M A Motaleb, Mai Mansour\",\"doi\":\"10.1080/10837450.2024.2323620\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cancer ranks as one of the most challenging illnesses to deal with because progressive phenotypic and genotypic alterations in cancer cells result in resistance and recurrence. Thus, the creation of novel medications or alternative therapy approaches is mandatory. Repurposing of old drugs is an attractive approach over the traditional drug discovery process in terms of shorter drug development duration, low-cost, highly efficient and minimum risk of failure. In this study Atorvastatin, a statin drug used to treat abnormal cholesterol levels and prevent cardiovascular disease in people at high risk, was introduced and encapsulated in cubic liquid crystals as anticancer candidate aiming at sustaining its release and achieving better cellular uptake in cancer cells. The cubic liquid crystals were successfully prepared and optimized with an entrapment effieciency of 73.57% ±1.35 and particle size around 200 nm. The selected formulae were effectively doped with radioactive iodine <sup>131</sup>I to enable the noninvasive visualization and trafficking of the new formulae. The <i>in vivo</i> evaluation in solid tumor bearing mice was conducted for comparing<sup>131</sup>I-Atorvastatin solution,<sup>131</sup>I-Atorvastatin loaded cubosome and <sup>131</sup>I-Atorvastatin chitosan coated cubosome. The <i>in vivo</i> biodistribution study revealed that tumor radioactivity uptake of <sup>131</sup>I-Atorvastatin cubosome and chitosan coated cubosome exhibited high accumulation in tumor tissues (target organ) scoring ID%/g of 5.67 ± 0.2 and 5.03 ± 0.1, respectively 1h post injection compared to drug solution which recorded 3.09 ± 0.05% 1h post injection. Concerning the targeting efficiency, the target/non target ratio for <sup>131</sup>I-Atorvastatin chitosan coated cubosome was higher than that of <sup>131</sup>I-Atorvastatin solution and <sup>131</sup>I ATV-loaded cubosome at all time intervals and recorded T/NT ratio of 2.908 2h post injection.</p>\",\"PeriodicalId\":20004,\"journal\":{\"name\":\"Pharmaceutical Development and Technology\",\"volume\":\" \",\"pages\":\"236-247\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical Development and Technology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/10837450.2024.2323620\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/9 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Development and Technology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10837450.2024.2323620","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/9 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Atorvastatin-loaded cubosome: a repurposed targeted delivery systems for enhanced targeting against breast cancer.
Cancer ranks as one of the most challenging illnesses to deal with because progressive phenotypic and genotypic alterations in cancer cells result in resistance and recurrence. Thus, the creation of novel medications or alternative therapy approaches is mandatory. Repurposing of old drugs is an attractive approach over the traditional drug discovery process in terms of shorter drug development duration, low-cost, highly efficient and minimum risk of failure. In this study Atorvastatin, a statin drug used to treat abnormal cholesterol levels and prevent cardiovascular disease in people at high risk, was introduced and encapsulated in cubic liquid crystals as anticancer candidate aiming at sustaining its release and achieving better cellular uptake in cancer cells. The cubic liquid crystals were successfully prepared and optimized with an entrapment effieciency of 73.57% ±1.35 and particle size around 200 nm. The selected formulae were effectively doped with radioactive iodine 131I to enable the noninvasive visualization and trafficking of the new formulae. The in vivo evaluation in solid tumor bearing mice was conducted for comparing131I-Atorvastatin solution,131I-Atorvastatin loaded cubosome and 131I-Atorvastatin chitosan coated cubosome. The in vivo biodistribution study revealed that tumor radioactivity uptake of 131I-Atorvastatin cubosome and chitosan coated cubosome exhibited high accumulation in tumor tissues (target organ) scoring ID%/g of 5.67 ± 0.2 and 5.03 ± 0.1, respectively 1h post injection compared to drug solution which recorded 3.09 ± 0.05% 1h post injection. Concerning the targeting efficiency, the target/non target ratio for 131I-Atorvastatin chitosan coated cubosome was higher than that of 131I-Atorvastatin solution and 131I ATV-loaded cubosome at all time intervals and recorded T/NT ratio of 2.908 2h post injection.
期刊介绍:
Pharmaceutical Development & Technology publishes research on the design, development, manufacture, and evaluation of conventional and novel drug delivery systems, emphasizing practical solutions and applications to theoretical and research-based problems. The journal aims to publish significant, innovative and original research to advance the frontiers of pharmaceutical development and technology.
Through original articles, reviews (where prior discussion with the EIC is encouraged), short reports, book reviews and technical notes, Pharmaceutical Development & Technology covers aspects such as:
-Preformulation and pharmaceutical formulation studies
-Pharmaceutical materials selection and characterization
-Pharmaceutical process development, engineering, scale-up and industrialisation, and process validation
-QbD in the form a risk assessment and DoE driven approaches
-Design of dosage forms and drug delivery systems
-Emerging pharmaceutical formulation and drug delivery technologies with a focus on personalised therapies
-Drug delivery systems research and quality improvement
-Pharmaceutical regulatory affairs
This journal will not consider for publication manuscripts focusing purely on clinical evaluations, botanicals, or animal models.