ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1556618
This article is part of the Research TopicAdvances in targeted therapeutics for gastrointestinal cancersView all 5 articles
Model-Based Prediction of Nanoparticle and Dissolved Form Ratios Using Total Concentration Data: A Case Study of SNB-101
Provisionally accepted
- 1AIMS BioScience, Co., Ltd, Seoul, Republic of Korea
- 2College of Medicine, Catholic University of Korea, Seoul, Republic of Korea
- 3SN BioScience, Inc., Seongnam-si, Gyeonggi-do, Republic of Korea
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Irinotecan (CPT-11), a topoisomerase I inhibitor, serves as a prodrug for SN-38, its active metabolite with significantly higher cytotoxic potency. Despite its clinical efficacy, irinotecan's therapeutic potential is limited by low fraction of conversion to inefficient tumor targeting, and dose-limiting toxicities such as diarrhea and neutropenia. Nanoparticle-based formulations, such as SNB-101, offer a promising solution by encapsulating irinotecan and SN-38, enhancing solubility, improving drug delivery efficiency, and reducing systemic toxicity through tumor-specific accumulation via the enhanced permeability and retention (EPR) effect. This study aimed to develop a pharmacokinetic (PK) model to differentiate between nanoparticle (NP) and dissolved (S) forms of irinotecan and SN-38 using total plasma concentration data from a Phase I clinical trial of SNB-101 (NCT04640480). The 11-compartment model incorporated prior knowledge of dissolved irinotecan PK and newly observed clinical data to characterize NP-to-S transitions and their respective contributions to total drug exposure. Results revealed that SNB-101 is predominantly predicted to deliver SN-38 in its nanoparticle form, with NP-SN-38 contributing over 80% of total SN-38 exposure. The high exposure to NP-SN-38 correlated with reduced systemic toxicity compared to conventional irinotecan formulations, despite significantly increased total SN-38 levels. This reduced exposure to dissolved SN-38 and irinotecan likely underpins the favorable safety profile observed in dose-escalation studies. This model-based approach underscores the utility of nanoparticle formulations in improving drug delivery and highlights the importance of distinguishing between NP and S forms for accurate efficacy and toxicity predictions. The framework may provide a useful tool for optimizing dose selection and accelerating the clinical development of nanoparticle-based therapeutics.
Keywords: SN-38, Nanoparticle drug delivery, Pharmacokinetic modeling, tumor targeting, Enhanced permeability and retention effect
Received: 16 May 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Park, Bae, Jeon, Park, Lee and Han. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Seunghoon Han, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.