1. TXB-001, a newly-developed polymer-conjugated anthracycline: Significantly lower adverse effects in animal models of alopecia and hand-foot syndrome.
- Author
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Hirakata M, Tomikawa E, Sakai C, Uchida M, Okano T, Shimozono R, Kawai M, Itaba S, Munakata L, Suzuki R, and Oshida K
- Subjects
- Animals, Female, Mice, Rats, Polymers chemistry, Polymers toxicity, Antibiotics, Antineoplastic toxicity, Rats, Sprague-Dawley, Anthracyclines toxicity, Anthracyclines adverse effects, Cell Line, Tumor, Male, Antineoplastic Agents toxicity, Polyethylene Glycols, Alopecia chemically induced, Alopecia drug therapy, Hand-Foot Syndrome etiology, Hand-Foot Syndrome drug therapy, Doxorubicin toxicity, Doxorubicin analogs & derivatives, Disease Models, Animal, Mice, Inbred BALB C
- Abstract
Anthracycline anti-cancer drugs have been widely used in the treatment of several cancers; however, their use is limited by adverse effects (AEs). Alopecia is a common AE that is minimally invasive, but adversely affects mental health and reduces quality of life (QoL). Hand-foot syndrome (HFS) is a dose-limiting AE of DOXIL, a liposomal formulation of doxorubicin (DOX). Although it is not a life-threatening condition, HFS affects function and reduces QoL. TXB-001 is a new candidate polymer-conjugated anthracycline anti-cancer drug, and modified and optimized polymerized pirarubicin (THP), known as P-THP, is expected to have low toxicity and high efficacy. The anti-cancer effects of TXB-001 were examined using the 4T1 mouse model. An alopecia mouse model and HFS rat model were used to evaluate the alopecia- and HFS-inducing effects of TXB-001 and compare their severity with existing anthracycline anti-cancer drugs. A pharmacokinetic analysis of plasma as well as chest, palmar, and plantar skin samples after the single intravenous administration of DOXIL and TXB-001 to rats was also performed. The results obtained revealed that TXB-001 exerted similar anti-cancer effects to those of DOXIL in mice, weaker alopecia-inducing effects than DOX, DOXIL, and THP in mice, and no or markedly weaker HFS-like changes than DOXIL, which induced significant histopathological changes. The results of the pharmacokinetic analysis showed the accumulation of DOXIL, but not TXB-001, in skin, particularly palmar and plantar skin samples, and these differences were considered to contribute to their HFS-inducing effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
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