title: Lower cytotoxicity, high stability, and long-term antibacterial activity of a poly(methacrylic acid)/isoniazid/rifampin nanogel against multidrug-resistant intestinal Mycobacterium tuberculosis.
abstract: To overcome the undesirable side effects and reduce the cytotoxicity of isoniazid (INH) and rifampin (RMP) in the digestive tract, a poly(methacrylic acid) (PMAA) nanogel was developed as a carrier of INH and RMP. This PMAA/INH/RMP nanogel was prepared as a treatment for intestinal tuberculosis caused by multidrug-resistant Mycobacterium tuberculosis (MTB). The morphology, size, and in vitro release properties were evaluated in a simulated gastrointestinal medium, and long-term antibacterial performance, cytotoxicity, stability, and activity of this novel PMAA/INH/RMP nanogel against multidrug-resistant MTB in the intestine were investigated. Our results indicate that the PMAA/INH/RMP nanogel exhibited extended antibacterial activity by virtue of its long-term release of INH and RMP in the simulated gastrointestinal medium. Further, this PMAA/INH/RMP nanogel exhibited lower cytotoxicity than did INH or RMP alone, suggesting that this PMAA/INH/RMP nanogel could be a more useful dosage form than separate doses of INH and RMP for intestinal MTB. The novel aspects of this study include the cytotoxicity study and the three-phase release profile study, which might be useful for other researchers in this field.
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, PR China; Key Laboratory of Translational Medicine of Guangdong, Guangzhou 510630, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of General Surgery of the First Affiliated Hospital of Jinan University, Guangzhou 510630, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Guangdong Provincial Hospital of Chinese Medicine, Guangdong 510120, PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Guo
authors.affiliation: Light Industry and Food Science, South China University of Technology, Guangzhou 510641, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Immunology, Medical College of Jinan University, Guangzhou 510632, PR China.
authors.forename: Zhenyan
authors.initials: Z
authors.lastname: Li
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, PR China; Key Laboratory of Translational Medicine of Guangdong, Guangzhou 510630, PR China.
authors.forename: Huixin
authors.initials: H
authors.lastname: Guo
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, PR China; Key Laboratory of Translational Medicine of Guangdong, Guangzhou 510630, PR China.
authors.forename: Haicheng
authors.initials: H
authors.lastname: Li
authors.affiliation: Bao'an Chronic Diseases Prevention and Cure Hospital, Shenzhen 518102, PR China.
authors.forename: Meigui
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, PR China; Key Laboratory of Translational Medicine of Guangdong, Guangzhou 510630, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, PR China; Key Laboratory of Translational Medicine of Guangdong, Guangzhou 510630, PR China.
authors.forename: Xunxun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, PR China; Key Laboratory of Translational Medicine of Guangdong, Guangzhou 510630, PR China. Electronic address: zhongqiu@vip.163.com.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, PR China; Key Laboratory of Translational Medicine of Guangdong, Guangzhou 510630, PR China. Electronic address: zhoulinpaper@vip.163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Light Chemical Engineering, Guangdong Polytechnic, Foshan 528041, PR China. Electronic address: angelwu2006@163.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004355:Drug Stability; D006801:Humans; D007538:Isoniazid / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D041681:NIH 3T3 Cells; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D011094:Polyethyleneimine / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000633:toxicity; D012293:Rifampin / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014385:Tuberculosis, Gastrointestinal / Q000382:microbiology*; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D000080385:Nanogels; D011109:Polymethacrylic Acids; C413692:polyethylene glycol polyethyleneimine nanogel; C030613:polymethacrylic acid; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D007538:Isoniazid; D012293:Rifampin
keywords: Cytotoxicity; Intestinal tuberculosis; Long-term activity; Multidrug-resistant Mycobacterium tuberculosis; Nanogel