Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo

Wei Hong,1 Xiang Gao,1 Peng Qiu,1 Jie Yang,1 Mingxi Qiao,2 Hong Shi,3 Dexian Zhang,1 Chunlian Tian,1 Shengli Niu,1 Mingchun Liu1 1Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenhe, Shenyang, Liaoning, People&...

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Autores principales:	Hong W, Gao X, Qiu P, Yang J, Qiao M, Shi H, Zhang D, Tian C, Niu S, Liu M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	bacitracin A poly (D L-lactide-co-glycolide) Nano-BAs broaden antibacterial spectrum wound healing Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0b825ba02bba4d04b1c2e42a9ab90491
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spelling	oai:doaj.org-article:0b825ba02bba4d04b1c2e42a9ab904912021-12-02T01:34:05ZSynthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo1178-2013https://doaj.org/article/0b825ba02bba4d04b1c2e42a9ab904912017-06-01T00:00:00Zhttps://www.dovepress.com/synthesis-construction-and-evaluation-of-self-assembled-nano-bacitraci-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wei Hong,1 Xiang Gao,1 Peng Qiu,1 Jie Yang,1 Mingxi Qiao,2 Hong Shi,3 Dexian Zhang,1 Chunlian Tian,1 Shengli Niu,1 Mingchun Liu1 1Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenhe, Shenyang, Liaoning, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Jiangning, Nanjing, 3Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China Abstract: Bacitracin A (BA) is an excellent polypeptide antibiotic that is active against gram-positive bacteria without triggering multidrug resistance. However, BA is inactive against gram-negative bacteria because of its inability to cross the outer membrane of these cells, and it has strong nephrotoxicity, thus limiting its clinical applications. Nanoantibiotics can effectively localize antibiotics to the periplasmic space of bacteria while decreasing the adverse effects of antibiotics. In this study, biodegradable hydrophobic copolymers of poly (D,L-lactide-co-glycolide) (PLGA) were attached to the N-termini of BA to design a novel class of self-assembled nano-bacitracin A (nano-BAs), and their potential as antibacterial agents was evaluated in vitro and in vivo. Nano-BAs had a core-shell structure with a mean diameter <150 nm. Impressively, nano-BAs had strong antibacterial properties against both gram-positive and gram-negative bacteria, and the distribution of antibacterial activity as a function of PLGA block length was skewed toward longer PLGA chains. No cytotoxicity against HK-2 cells or human red blood cells (hRBCs) was observed in vitro, suggesting good biocompatibility. A high local density of BA mass on the surface promoted endocytotic cellular uptake, and hydrophobic interactions between the PLGA block and lipopolysaccharide (LPS) facilitated the uptake of nano-BAs, thereby leading to greater antibacterial activities. In addition, Nano-BA5K was found to be effective in vivo, and it served as an anti-infective agent for wound healing. Collectively, this study provides a cost-effective means of developing self-assembling nano-polypeptide antibiotic candidates with a broader antibacterial spectrum and a lower toxicity than commercially available peptide antibiotics, owing to their modification with biodegradable copolymers. Keywords: bacitracin A, poly (D,L-lactide-co-glycolide), nano-BAs, broader antibacterial spectrum, wound healingHong WGao XQiu PYang JQiao MShi HZhang DTian CNiu SLiu MDove Medical Pressarticlebacitracin Apoly (DL-lactide-co-glycolide)Nano-BAsbroaden antibacterial spectrumwound healingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 4691-4708 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacitracin A poly (D L-lactide-co-glycolide) Nano-BAs broaden antibacterial spectrum wound healing Medicine (General) R5-920
spellingShingle	bacitracin A poly (D L-lactide-co-glycolide) Nano-BAs broaden antibacterial spectrum wound healing Medicine (General) R5-920 Hong W Gao X Qiu P Yang J Qiao M Shi H Zhang D Tian C Niu S Liu M Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo
description	Wei Hong,1 Xiang Gao,1 Peng Qiu,1 Jie Yang,1 Mingxi Qiao,2 Hong Shi,3 Dexian Zhang,1 Chunlian Tian,1 Shengli Niu,1 Mingchun Liu1 1Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenhe, Shenyang, Liaoning, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Jiangning, Nanjing, 3Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China Abstract: Bacitracin A (BA) is an excellent polypeptide antibiotic that is active against gram-positive bacteria without triggering multidrug resistance. However, BA is inactive against gram-negative bacteria because of its inability to cross the outer membrane of these cells, and it has strong nephrotoxicity, thus limiting its clinical applications. Nanoantibiotics can effectively localize antibiotics to the periplasmic space of bacteria while decreasing the adverse effects of antibiotics. In this study, biodegradable hydrophobic copolymers of poly (D,L-lactide-co-glycolide) (PLGA) were attached to the N-termini of BA to design a novel class of self-assembled nano-bacitracin A (nano-BAs), and their potential as antibacterial agents was evaluated in vitro and in vivo. Nano-BAs had a core-shell structure with a mean diameter <150 nm. Impressively, nano-BAs had strong antibacterial properties against both gram-positive and gram-negative bacteria, and the distribution of antibacterial activity as a function of PLGA block length was skewed toward longer PLGA chains. No cytotoxicity against HK-2 cells or human red blood cells (hRBCs) was observed in vitro, suggesting good biocompatibility. A high local density of BA mass on the surface promoted endocytotic cellular uptake, and hydrophobic interactions between the PLGA block and lipopolysaccharide (LPS) facilitated the uptake of nano-BAs, thereby leading to greater antibacterial activities. In addition, Nano-BA5K was found to be effective in vivo, and it served as an anti-infective agent for wound healing. Collectively, this study provides a cost-effective means of developing self-assembling nano-polypeptide antibiotic candidates with a broader antibacterial spectrum and a lower toxicity than commercially available peptide antibiotics, owing to their modification with biodegradable copolymers. Keywords: bacitracin A, poly (D,L-lactide-co-glycolide), nano-BAs, broader antibacterial spectrum, wound healing
format	article
author	Hong W Gao X Qiu P Yang J Qiao M Shi H Zhang D Tian C Niu S Liu M
author_facet	Hong W Gao X Qiu P Yang J Qiao M Shi H Zhang D Tian C Niu S Liu M
author_sort	Hong W
title	Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo
title_short	Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo
title_full	Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo
title_fullStr	Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo
title_full_unstemmed	Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo
title_sort	synthesis, construction, and evaluation of self-assembled nano-bacitracin a as an efficient antibacterial agent in vitro and in vivo
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/0b825ba02bba4d04b1c2e42a9ab90491
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Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo

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