---
title: "TPGS-stabilized pyrimethamine micelles induce ROS-mediated apoptosis and slow tumour growth"
id: "pubmed-42700206"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42700206"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42700206/"
doi: "10.1007/s40199-026-00656-4"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# TPGS-stabilized pyrimethamine micelles induce ROS-mediated apoptosis and slow tumour growth
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42700206
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42700206/)
- **DOI:** [10.1007/s40199-026-00656-4](https://doi.org/10.1007%2Fs40199-026-00656-4)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- A TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate)-based micellar formulation of **pyrimethamine**, a dihydrofolate reductase inhibitor with emerging anticancer potential, was developed to address poor aqueous solubility and bioavailability. - Micelles were prepared by solvent casting–rehydration and characterized by DLS, AFM, SEM and TEM; the optimized formulation produced homogeneous spherical micelles with an average diameter of ~74 nm and a low polydispersity index (0.20). - In physiological conditions the formulation exhibited persistent biphasic drug release, indicating sustained delivery potential compared with free drug. - In MDA-MB-231 breast cancer cells, TPGS-stabilized pyrimethamine micelles increased cytotoxicity and intracellular uptake relative to free pyrimethamine. - Mechanistic in vitro studies linked the nanoformulation’s effects to elevated **reactive oxygen species (ROS)**, increased Annexin V–positive apoptotic cell populations, and G2/M cell-cycle arrest, consistent with ROS-associated apoptosis and cell-cycle disruption. - In a murine lymphoma model the nanoformulation reduced tumour progression and achieved 100% survival through Day 30 in treated animals. - Authors conclude that these preclinical data support further evaluation of **TPGS-based pyrimethamine micelles** for anticancer delivery, while noting that additional studies of mechanism, pharmacokinetics, long-term safety, and efficacy in breast-cancer-specific animal models are required. - Ethical oversight: IAEC approval reported (BHU/DoZ/IAEC/2021-2022/014) with 40 Swiss Albino BALB/c mice (20 male, 20 female) approved for the third year; authors declared no competing interests.
## Clinical Analysis & Structured Key Points
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Y. Patil Medical College, Hospital and Research Centre, Pune, India."), [Surya Nath Pandey](https://pubmed.ncbi.nlm.nih.gov/?term=Pandey+SN&cauthor_id=42700206)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42700206/#full-view-affiliation-4 "Department of Pharmacology, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, 244001, Moradabad, India."), [Amit Patel](https://pubmed.ncbi.nlm.nih.gov/?term=Patel+A&cauthor_id=42700206)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42700206/#full-view-affiliation-5 "Banaras Hindu University, Varanasi, India."), [Ashish Kumar Tewari](https://pubmed.ncbi.nlm.nih.gov/?term=Tewari+AK&cauthor_id=42700206)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42700206/#full-view-affiliation-5 "Banaras Hindu University, Varanasi, India."), [Priyanka Sonker](https://pubmed.ncbi.nlm.nih.gov/?term=Sonker+P&cauthor_id=42700206)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42700206/#full-view-affiliation-6 "Department of Pharmacy, Institute of Technology and Management, GIDA, Gorakhpur, Uttar Pradesh, 273209, India. priyankasonker2016@gmail.com.") Affiliations Expand ### Affiliations * 1 Department of Pharmacy, Institute of Technology and Management, GIDA, Gorakhpur, Uttar Pradesh, 273209, India. * 2 Center for innovation and inclusive research, Sharda University, 201306, Greater Noida, India. * 3 Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India. * 4 Department of Pharmacology, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, 244001, Moradabad, India. * 5 Banaras Hindu University, Varanasi, India. * 6 Department of Pharmacy, Institute of Technology and Management, GIDA, Gorakhpur, Uttar Pradesh, 273209, India. priyankasonker2016@gmail.com. * PMID: **42700206** * DOI: [ 10.1007/s40199-026-00656-4 ](https://doi.org/10.1007/s40199-026-00656-4) Item in Clipboard # TPGS-stabilized pyrimethamine micelles promote ROS-associated apoptosis in MDA-MB-231 cells and suppress tumour progression in a murine lymphoma model Indrajeet Yadav et al. Daru. 2026. Show details Display options Display options Format Abstract PubMed PMID Daru Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Daru%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Daru%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700206/) . 2026 Sep 5;34(2):69. doi: 10.1007/s40199-026-00656-4. ### Authors [Indrajeet Yadav](https://pubmed.ncbi.nlm.nih.gov/?term=Yadav+I&cauthor_id=42700206)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42700206/#short-view-affiliation-1 "Department of Pharmacy, Institute of Technology and Management, GIDA, Gorakhpur, Uttar Pradesh, 273209, India."), [Manisha Nidhar](https://pubmed.ncbi.nlm.nih.gov/?term=Nidhar+M&cauthor_id=42700206)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42700206/#short-view-affiliation-2 "Center for innovation and inclusive research, Sharda University, 201306, Greater Noida, India."), [Pavan Goud](https://pubmed.ncbi.nlm.nih.gov/?term=Goud+P&cauthor_id=42700206)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42700206/#short-view-affiliation-3 "Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India."), [Surya Nath Pandey](https://pubmed.ncbi.nlm.nih.gov/?term=Pandey+SN&cauthor_id=42700206)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42700206/#short-view-affiliation-4 "Department of Pharmacology, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, 244001, Moradabad, India."), [Amit Patel](https://pubmed.ncbi.nlm.nih.gov/?term=Patel+A&cauthor_id=42700206)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42700206/#short-view-affiliation-5 "Banaras Hindu University, Varanasi, India."), [Ashish Kumar Tewari](https://pubmed.ncbi.nlm.nih.gov/?term=Tewari+AK&cauthor_id=42700206)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42700206/#short-view-affiliation-5 "Banaras Hindu University, Varanasi, India."), [Priyanka Sonker](https://pubmed.ncbi.nlm.nih.gov/?term=Sonker+P&cauthor_id=42700206)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42700206/#short-view-affiliation-6 "Department of Pharmacy, Institute of Technology and Management, GIDA, Gorakhpur, Uttar Pradesh, 273209, India. priyankasonker2016@gmail.com.") ### Affiliations * 1 Department of Pharmacy, Institute of Technology and Management, GIDA, Gorakhpur, Uttar Pradesh, 273209, India. * 2 Center for innovation and inclusive research, Sharda University, 201306, Greater Noida, India. * 3 Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India. * 4 Department of Pharmacology, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, 244001, Moradabad, India. * 5 Banaras Hindu University, Varanasi, India. * 6 Department of Pharmacy, Institute of Technology and Management, GIDA, Gorakhpur, Uttar Pradesh, 273209, India. priyankasonker2016@gmail.com. * PMID: **42700206** * DOI: [ 10.1007/s40199-026-00656-4 ](https://doi.org/10.1007/s40199-026-00656-4) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** A dihydrofolate reductase inhibitor, pyrimethamine has an emerging anticancer potential but is not well soluble in aqueous and bioavailable. The D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-based micellar nanoformulation was developed to overcome these challenges to improve its therapeutic performance. **Objective:** The D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-based micellar nanoformulation was developed to overcome these challenges to improve its therapeutic performance. **Methods:** TPGS micelles containing pyrimethamine were developed through solvent casting-rehydration and studied through DLS, AFM, SEM and TEM. **Results:** The maximally efficient expression generated homogeneous spherical micelles with an average diameter of about 74 nm and a low polydispersity (0.20) that is very homogeneous and stable. Persistent bi-phasic drug delivery was seen in physiological conditions. TPGS-Stabilized Pyrimethamine Micelles Promote ROS-Associated Apoptosis. In MDA-MB-231 breast cancer cells, the nanoformulation increased cytotoxicity and intracellular uptake compared with free pyrimethamine. The experiment showed that in mechanistic studies, there was high production of reactive oxygen species, high Annexin V-positive populations of apoptotic cells and G2/M phase arrest, which were associated with increased ROS generation, apoptosis, and cell-cycle arrest. In the murine lymphoma model, the nanoformulation reduced tumour progression and resulted in 100% survival through Day 30. **Conclusion:** These findings support further preclinical investigation of TPGS-based pyrimethamine micelles as a potential anticancer delivery strategy. Additional studies are required to confirm their mechanism, pharmacokinetic behaviour, long-term safety, and efficacy in breast-cancer-specific animal models. **Keywords:** Apoptosis; Cell-cycle arrest; MDA-MB-231 cells; Murine lymphoma model; Nanomedicine; Pyrimethamine; Reactive oxygen species; TPGS micelles. © 2026. The Author(s), under exclusive licence to Tehran University of Medical Sciences. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Ethics approval and consent to participate: IAEC Approval Reference No. BHU/DoZ/IAEC/2021-2022/014 Date of IAEC meeting held : 15.02.2022 Project code number : IAEC/2021-22/14 Funding source & its status (Applied/Approved) : UGC-BHU Fellowship Title of the research project : Synthesis of bioactive molecules and their antiproliferative efficacy in cancer cells. Name of the Principal Investigator and/or other associated staff & Position : Dr. Biplob Koch, Associate Professor, Department of Zoology; Dr A K Tewari, Professor; Ms. Priyanka Sonker, Department of Chemistry, BHU Duration of the approved project : 3 Year IAEC approval status of the protocol : Approved Animal sp. /strain/age/sex etc and numbers approved by the IAEC Year-wise: 1st year: Nil mice, 2nd year Nil mice, 3rd year 20 male & 20 female Swiss Albino BALb/c mice (total 40 Swiss Albino BALb/c mice) 1st year sanction: NIL Expiry period of IAEC approval :Three Years 1. Human-subjects accordance statement: “Not applicable. This study did not involve human participants, human biological samples, or human-derived data. The study involved animals only.” 2. Human research ethics approval statement: “Not applicable. No human participants were involved in this study; therefore, human research ethics approval was not required.” 3. Informed-consent statement: “Not applicable. The study did not involve human participants; therefore, informed consent was not required.” Competing interest: The authors declare no competing interests. ## References 1. 1. Gottesman MM, et al. Mechanisms of cancer drug resistance. Nat Rev Cancer. 2002. . - [DOI](https://doi.org/10.1038/nrc706) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/11902585/) 2. 1. Holohan C, et al. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer. 2013. . - [DOI](https://doi.org/10.1038/nrc3599) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/24060863/) 3. 1. Longley DB, Johnston PG, et al. Molecular mechanisms of drug resistance. J Pathol. 2005. . - [DOI](https://doi.org/10.1002/path.1701) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/15641020/) 4. 1. Assaraf YG, et al. Molecular basis of antifolate resistance. Cancer Metastasis Rev. 2007. . - [DOI](https://doi.org/10.1007/s10555-007-9067-6) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/17333344/) 5. 1. Szakács G, et al. Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 2006. . - [DOI](https://doi.org/10.1038/nrd1984) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/16518375/) Show all 36 references ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700206/) * Antineoplastic Agents* / administration & dosage Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Antineoplastic+Agents%2Fadministration+and+dosage%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Antineoplastic+Agents) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700206/) * Antineoplastic Agents* / chemistry Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Antineoplastic+Agents%2Fchemistry%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Antineoplastic+Agents) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700206/) * Antineoplastic Agents* / pharmacology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Antineoplastic+Agents%2Fpharmacology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Antineoplastic+Agents) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700206/) * Apoptosis / drug effects Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Apoptosis%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Apoptosis) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700206/) * Cell Line, Tumor Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Line%2C+Tumor%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Line%2C+Tumor) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700206/) * Female Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Female) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700206/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700206/) * Lymphoma* / drug therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Lymphoma%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Lymphoma) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700206/) * Lymphoma* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Lymphoma%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Lymphoma) * [ Add to Search ](https:
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