Development and Characterization of Optimized Drug-Loaded Niosomes for Delivery of 5-FU and Irinotecan
<b>Background/Objectives</b>: 5-Fluorouracil (5-FU) and Irinotecan (IRT) are two of the most used chemotherapeutic agents in CRC treatment. However, achieving treatment goals has been hampered by poor drug delivery to tumor sites and associated toxicity from off-target binding to healthy...
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2025-07-01
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| author | Kafilat O. Agbaje Simeon K. Adesina Amusa S. Adebayo |
| author_facet | Kafilat O. Agbaje Simeon K. Adesina Amusa S. Adebayo |
| author_sort | Kafilat O. Agbaje |
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| description | <b>Background/Objectives</b>: 5-Fluorouracil (5-FU) and Irinotecan (IRT) are two of the most used chemotherapeutic agents in CRC treatment. However, achieving treatment goals has been hampered by poor drug delivery to tumor sites and associated toxicity from off-target binding to healthy cells. Though the synergism of 5-FU-IRT has provided incremental improvements in clinical outcomes, the short elimination half-life and off-target binding to healthy cells remain significant challenges. We postulated that nanoencapsulation of a combination of 5-FU and IRT in niosomes would prolong the drugs’ half-lives, while over-encapsulation lyophilized powder in Targit<sup>®</sup> oral capsules would passively the CRC microenvironment and avoid extensive systemic distribution. <b>Methods</b>: Ranges of formulation and process variables were input into design of experiment (DOE Fusion One) software, to generate screening experiments. Niosomes were prepared using the thin-film hydration method and characterized by size, the polydispersity index (PDI), morphology and intrastructure, and drug loading. Blank niosomes ranged in size from 215 nm to 257 nm. <b>Results:</b> After loading with the 5-FU-IRT combination, the niosomes averaged 251 ± 2.20 nm with a mean PDI of 0.293 ± 0.01. The surfactant-to-cholesterol ratio significantly influenced the niosome size and the PDI. The hydrophilic 5-FU exhibited superior loading compared to the lipophilic IRT molecules, which probably competed with other lipophilic niosome components in niosomes’ palisade layers. In vitro dissolution in biorelevant media showed delayed release until lower intestinal region (IRT) or colonic region (5-FU). <b>Conclusions:</b> Thus, co-nanoencapsulation of 5-FU/IRT in niosomes, lyophilization, and over-encapsulation of powder in colon-specific capsules could passively target the CRC cells in the colonic microenvironment. |
| format | Article |
| id | doaj-art-07be4576c52541eb91f7a2a829470d4b |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-07be4576c52541eb91f7a2a829470d4b2025-08-20T03:32:15ZengMDPI AGPharmaceutics1999-49232025-07-0117790010.3390/pharmaceutics17070900Development and Characterization of Optimized Drug-Loaded Niosomes for Delivery of 5-FU and IrinotecanKafilat O. Agbaje0Simeon K. Adesina1Amusa S. Adebayo2Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, 2300 4th Street NW, Washington, DC 20059, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Howard University, 2300 4th Street NW, Washington, DC 20059, USADepartment of Pharmaceutical Sciences, College of Pharmacy, Howard University, 2300 4th Street NW, Washington, DC 20059, USA<b>Background/Objectives</b>: 5-Fluorouracil (5-FU) and Irinotecan (IRT) are two of the most used chemotherapeutic agents in CRC treatment. However, achieving treatment goals has been hampered by poor drug delivery to tumor sites and associated toxicity from off-target binding to healthy cells. Though the synergism of 5-FU-IRT has provided incremental improvements in clinical outcomes, the short elimination half-life and off-target binding to healthy cells remain significant challenges. We postulated that nanoencapsulation of a combination of 5-FU and IRT in niosomes would prolong the drugs’ half-lives, while over-encapsulation lyophilized powder in Targit<sup>®</sup> oral capsules would passively the CRC microenvironment and avoid extensive systemic distribution. <b>Methods</b>: Ranges of formulation and process variables were input into design of experiment (DOE Fusion One) software, to generate screening experiments. Niosomes were prepared using the thin-film hydration method and characterized by size, the polydispersity index (PDI), morphology and intrastructure, and drug loading. Blank niosomes ranged in size from 215 nm to 257 nm. <b>Results:</b> After loading with the 5-FU-IRT combination, the niosomes averaged 251 ± 2.20 nm with a mean PDI of 0.293 ± 0.01. The surfactant-to-cholesterol ratio significantly influenced the niosome size and the PDI. The hydrophilic 5-FU exhibited superior loading compared to the lipophilic IRT molecules, which probably competed with other lipophilic niosome components in niosomes’ palisade layers. In vitro dissolution in biorelevant media showed delayed release until lower intestinal region (IRT) or colonic region (5-FU). <b>Conclusions:</b> Thus, co-nanoencapsulation of 5-FU/IRT in niosomes, lyophilization, and over-encapsulation of powder in colon-specific capsules could passively target the CRC cells in the colonic microenvironment.https://www.mdpi.com/1999-4923/17/7/900niosomes5-fluorouracilIrinotecanbiorelevant dissolution |
| spellingShingle | Kafilat O. Agbaje Simeon K. Adesina Amusa S. Adebayo Development and Characterization of Optimized Drug-Loaded Niosomes for Delivery of 5-FU and Irinotecan Pharmaceutics niosomes 5-fluorouracil Irinotecan biorelevant dissolution |
| title | Development and Characterization of Optimized Drug-Loaded Niosomes for Delivery of 5-FU and Irinotecan |
| title_full | Development and Characterization of Optimized Drug-Loaded Niosomes for Delivery of 5-FU and Irinotecan |
| title_fullStr | Development and Characterization of Optimized Drug-Loaded Niosomes for Delivery of 5-FU and Irinotecan |
| title_full_unstemmed | Development and Characterization of Optimized Drug-Loaded Niosomes for Delivery of 5-FU and Irinotecan |
| title_short | Development and Characterization of Optimized Drug-Loaded Niosomes for Delivery of 5-FU and Irinotecan |
| title_sort | development and characterization of optimized drug loaded niosomes for delivery of 5 fu and irinotecan |
| topic | niosomes 5-fluorouracil Irinotecan biorelevant dissolution |
| url | https://www.mdpi.com/1999-4923/17/7/900 |
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