PMID- 38521368
OWN - NLM
STAT- MEDLINE
DCOM- 20240426
LR  - 20240426
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 485
DP  - 2024 Apr
TI  - TXB-001, a newly-developed polymer-conjugated anthracycline: Significantly lower 
      adverse effects in animal models of alopecia and hand-foot syndrome.
PG  - 116912
LID - S0041-008X(24)00110-8 [pii]
LID - 10.1016/j.taap.2024.116912 [doi]
AB  - 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.
CI  - Copyright (c) 2024. Published by Elsevier Inc.
FAU - Hirakata, Mikito
AU  - Hirakata M
AD  - Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, 
      Kamakura, Kanagawa 248-8555, Japan.
FAU - Tomikawa, Emi
AU  - Tomikawa E
AD  - Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, 
      Kamakura, Kanagawa 248-8555, Japan.
FAU - Sakai, Chizuka
AU  - Sakai C
AD  - Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, 
      Kamakura, Kanagawa 248-8555, Japan.
FAU - Uchida, Masashi
AU  - Uchida M
AD  - Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, 
      Kamakura, Kanagawa 248-8555, Japan.
FAU - Okano, Tsubasa
AU  - Okano T
AD  - Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, 
      Kamakura, Kanagawa 248-8555, Japan.
FAU - Shimozono, Rieko
AU  - Shimozono R
AD  - Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, 
      Kamakura, Kanagawa 248-8555, Japan.
FAU - Kawai, Masakatsu
AU  - Kawai M
AD  - Department of Bio Research, Kamakura Techno-Science, Inc., 6-10-1 Tebiro, 
      Kamakura, Kanagawa, 248-0036, Japan.
FAU - Itaba, Shoichi
AU  - Itaba S
AD  - Department of Bio Research, Kamakura Techno-Science, Inc., 6-10-1 Tebiro, 
      Kamakura, Kanagawa, 248-0036, Japan.
FAU - Munakata, Lisa
AU  - Munakata L
AD  - Laboratory of Drug and Gene Delivery Research, Faculty of Pharma-Science, Teikyo 
      University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
FAU - Suzuki, Ryo
AU  - Suzuki R
AD  - Laboratory of Drug and Gene Delivery Research, Faculty of Pharma-Science, Teikyo 
      University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
FAU - Oshida, Keiyu
AU  - Oshida K
AD  - Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, 
      Kamakura, Kanagawa 248-8555, Japan.. Electronic address: 
      keiyu.oshida.h5@mail.toray.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240322
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 80168379AG (Doxorubicin)
RN  - 0 (Polymers)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Anthracyclines)
RN  - 0 (liposomal doxorubicin)
RN  - 0 (Antineoplastic Agents)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
SB  - IM
MH  - Animals
MH  - *Alopecia/chemically induced/drug therapy
MH  - *Hand-Foot Syndrome/etiology/drug therapy
MH  - *Doxorubicin/toxicity/*analogs & derivatives
MH  - Female
MH  - Mice
MH  - *Disease Models, Animal
MH  - Rats
MH  - *Mice, Inbred BALB C
MH  - Polymers/chemistry/toxicity
MH  - Antibiotics, Antineoplastic/toxicity
MH  - Rats, Sprague-Dawley
MH  - Anthracyclines/toxicity/adverse effects
MH  - Cell Line, Tumor
MH  - Male
MH  - Antineoplastic Agents/toxicity
MH  - Polyethylene Glycols
OTO - NOTNLM
OT  - Alopecia
OT  - Anthracycline Anti-cancer Drugs
OT  - Hand-Foot Syndrome
COIS- 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.
EDAT- 2024/03/24 00:42
MHDA- 2024/04/27 09:50
CRDT- 2024/03/23 20:41
PHST- 2023/12/12 00:00 [received]
PHST- 2024/03/05 00:00 [revised]
PHST- 2024/03/20 00:00 [accepted]
PHST- 2024/04/27 09:50 [medline]
PHST- 2024/03/24 00:42 [pubmed]
PHST- 2024/03/23 20:41 [entrez]
AID - S0041-008X(24)00110-8 [pii]
AID - 10.1016/j.taap.2024.116912 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2024 Apr;485:116912. doi: 10.1016/j.taap.2024.116912. 
      Epub 2024 Mar 22.