Development of a PAMAM Dendrimer for Sustained Release of Temozolomide against Experimental Murine Lymphoma: Assessment of Therapeutic Efficacy
| Autor: | Sumit Kumar Hira, Ugir Hossain Sk, Abhinandan Rej, Debapriya RoyMahapatra, Partha Pratim Manna |
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| Rok vydání: | 2021 |
| Předmět: |
Drug
Dendrimers Lymphoma Cell Survival media_common.quotation_subject Biomedical Engineering Apoptosis Biocompatible Materials Biomaterials Mice PAMAM dendrimer Drug Development Cell Line Tumor Materials Testing Temozolomide medicine Animals Humans Particle Size Solid tumor Antineoplastic Agents Alkylating Cell Proliferation media_common Molecular Structure Murine lymphoma Chemistry Biochemistry (medical) Neoplasms Experimental General Chemistry medicine.disease Drug Liberation Toxicity Cancer research Female Drug Screening Assays Antitumor medicine.drug |
| Zdroj: | ACS Applied Bio Materials. 4:2628-2638 |
| ISSN: | 2576-6422 |
| DOI: | 10.1021/acsabm.0c01599 |
| Popis: | Enhanced drug localization at the tumor sites with minimal toxicity was demonstrated using dendrimer-conjugated temozolomide for treating experimental lymphoma, developed as a solid tumor. Herein, we have constructed a polyamidoamine (PAMAM) dendrimer conjugated with temozolomide to enhance the stability of the active drug metabolites, derived from the prodrug temozolomide. Our results suggest that the active drug (5-(3-methyltriazen-1-yl)imidazole-4-carboxamide) (MTIC) (derived from temozolomide) showed stable and sustained release from the dendrimer-temozolomide conjugate, suggesting the suitability of the construct for therapy. Besides growth inhibition and direct killing, the dendrimer-temozolomide construct induced extensive apoptosis not only in parental Dalton lymphoma tumor cells but also in the doxorubicin-resistant form of the tumor cells. Dendrimer-temozolomide conjugation significantly reduced the solid tumor growth and increased the lifespan with better prognosis, including improved histopathology of the treated mice, while untreated littermates developed extensive metastasis and succumbed to death. |
| Databáze: | OpenAIRE |
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