Worm-like micelles facilitate the intestinal mucus diffusion and drug accumulation for enhancing colorectal cancer therapy

Yihan Zhou ¹Duo Gao ²Yaying Wang ²Li Liang ³Qingyu Zhang ³Wenwen Han ³Jie Wang ⁴Chunliu Zhu ⁵Xinxin Zhang ⁶Yong Gan⁷

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作者信息

1. State Key Laboratory of Drug Research and Center of Pharmaceutics,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China
2. State Key Laboratory of Drug Research and Center of Pharmaceutics,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;University of Chinese Academy of Sciences,Beijing 100049,China
3. School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China
4. State Key Laboratory of Drug Research and Center of Pharmaceutics,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China
5. State Key Laboratory of Drug Research and Center of Pharmaceutics,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China
6. State Key Laboratory of Drug Research and Center of Pharmaceutics,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China;University of Chinese Academy of Sciences,Beijing 100049,China
7. State Key Laboratory of Drug Research and Center of Pharmaceutics,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China;University of Chinese Academy of Sciences,Beijing 100049,China;NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients,National Institutes for Food and Drug Control,Beijing 100050,China
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Abstract

Local delivery of nanoparticles holds promise for colorectal cancer(CRC)therapy.However,the pres-ence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby ad-versely affecting treatment efficiency.It is crucial to develop efficient drug delivery carriers that can effectively overcome mucus barriers to treat colorectal cancer.Herein,we utilized poly(1,4-butadiene)-b-poly(ethylene oxide)polymers to prepare four distinct geometries of polymeric micelles,namely linear micelles(LMs),worm-like micelles(WLMs),large spherical micelles(LSMs),and small spherical micelles(SSMs)to investigate the influence of shape effects on overcoming colonic mucosal barrier.We found that the carriers exhibited diverse shapes while maintaining comparable physicochemical properties.Of these,WLMs had an aspect ratio similar to segmented filamentous bacteria,which exhibited superior mucus penetration ability,leading to prolonged drug release kinetics and faster entry into epithelial cells com-pared to LSMs.Furthermore,rectally administrated 10-hydroxycamptothecin-loaded WLMs traversed the colorectal mucus in orthotopic CRC nude mice model,penetrated and accumulated within tumor tissue,and effectively aggregated within cancer cells,thereby inducing significantly robust antitumor outcomes in vivo.These findings underscore the significance of shape design in overcoming colonic mucosal absorp-tion barriers,offering a novel approach for the development of drug delivery carriers tailored for effective tumor therapy.

Key words

Worm-like micelles/Mucus penetration/Shape dependent/Transmucosal delivery/Colorectal cancer

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基金项目

National Natural Science Foundation of China(82003678)

National Natural Science Foundation of China(82222066)

National Natural Science Foundation of China(82025032)

Chinese Pharmacopoeia Commission(2021Y30)

出版年

2024

中国化学快报(英文版)

中国化学会

中国化学快报(英文版)

CSTPCDCSCD

影响因子：0.771

ISSN：1001-8417

参考文献量1

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