Albumin-based nanoparticles encapsulating SN-38 demonstrate superior antitumor efficacy compared to irinotecan
Efficient formulation of SN-38 for broad-spectrum chemotherapy remains an unmet medical need. The limited solubility of SN-38 in both aqueous and organic solvents poses a major challenge for formulation development. As a result, the predominant strategy, polymer-SN-38 drug conjugates, often involves...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
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| Series: | Drug Delivery |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2025.2545519 |
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| Summary: | Efficient formulation of SN-38 for broad-spectrum chemotherapy remains an unmet medical need. The limited solubility of SN-38 in both aqueous and organic solvents poses a major challenge for formulation development. As a result, the predominant strategy, polymer-SN-38 drug conjugates, often involves complex synthetic procedures and low drug loading (1–5% w/w). Such limitations hinder their large-scale production and clinical translation. In this study, we developed an encapsulation strategy that utilizes the reversible lactone–carboxylate equilibrium of SN-38 to simplify the formulation process and achieve enhanced drug loading. The major issue of SN-38 solubility in organic solvents was effectively addressed by sodium hydroxide (NaOH)-induced conversion of the lactone to the carboxylate form. We have demonstrated that SN-38 carboxylate, once encapsulated within human serum albumin–polylactic acid (HSA–PLA) nanoparticles, retains its reversibility and can be converted back to the active lactone form simply by the addition of hydrochloric acid (HCl). The drug loading capacity of SN-38 in the HSA–PLA nanoparticles was increased to 19% w/w. In vitro cytotoxicity assays confirmed that HSA–PLA (SN-38) nanoparticles exhibited significantly lower IC50 values (0.5–194 nM) across multiple cancer cell lines compared to the clinical standard, irinotecan (CPT-11), indicating superior potency under physiological conditions. In vivo studies in 4T1 and MDA-MB-231 tumor-bearing mice further validated the enhanced therapeutic efficacy of this formulation. Overall, this study presents a promising alternative strategy for SN-38 delivery via encapsulation rather than polymer–drug conjugation, significantly simplifying the formulation process and enhancing the translational potential of SN-38 for broad chemotherapeutic applications. |
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| ISSN: | 1071-7544 1521-0464 |