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Carbohydr Polym. 2018 Oct 1;197:403-413. doi: 10.1016/j.carbpol.2018.06.034. Epub 2018 Jun 7.

Genipin-crosslinked carboxymethyl chitosan nanogel for lung-targeted delivery of isoniazid and rifampin.

Author information

1
Department of Light Chemical Engineering, Guangdong Polytechnic, Foshan 528041, PR China.
2
Foshan Fourth People's Hospital, Foshan 528000, PR China.
3
Shenzhen Center For Chronic Disease Control, Shenzhen 518102, PR China.
4
Scientific Research Office, Guangdong Polytechnic, Foshan 528041, PR China.
5
Department of Clinical Nutrition, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China.
6
Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, PR China; South China Institute of Biomedicine, Guangzhou 510535, PR China.
7
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, PR China. Electronic address: madong_jnu@163.com.
8
Shenzhen Center For Chronic Disease Control, Shenzhen 518102, PR China. Electronic address: ywy2002@126.com.
9
Department of Light Chemical Engineering, Guangdong Polytechnic, Foshan 528041, PR China. Electronic address: cecaixiang@163.com.

Abstract

Lung-targeted genipin-crosslinked deacetylated chitosan (GEN-CS)/isoniazid (INH)/rifampin (RMP) nanogel particles (NGPs) were prepared as a treatment for tuberculosis caused by multidrug-resistant Mycobacterium tuberculosis (MTB) to surmount the undesirable side effects and decrease the cytotoxicity of INH and RMP when being against MTB. The size, morphology, in vitro release property, long-term antibacterial performance, stability, in vitro cytotoxicity, in vivo toxicity, and in vivo release property of GEN-CS/INH/RMP NGPs inhalation powder were investigated. The results showed that the GEN-CS/INH/RMP NGPs inhalation powder exhibited extended antibacterial activity because of its long-term release of INH and RMP. A simplex GEN-CS/INH/RMP NGPs pulmonary dose led to the therapeutic drug concentration of 40%-60% in lung and other organs (<5%) for 24 h. Furthermore, this GEN-CS/INH/RMP NGPs lyophilized inhalation powder displayed lung-targeted property and lower in vivo toxicity. These results suggested that this GEN-CS/INH/RMP NGPs inhalation powder would be a more useful dosage form than separate dose of INH or RMP for MTB.

KEYWORDS:

Antibacterial; Lung target; Multidrug-resistant; Nanogel; Toxicity; Tuberculosis

PMID:
30007629
DOI:
10.1016/j.carbpol.2018.06.034
[Indexed for MEDLINE]

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