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Titolo:
A novel microbial infection-responsive drug release system
Autore:
Tanihara, M; Suzuki, Y; Nishimura, Y; Suzuki, K; Kakimaru, Y; Fukunishi, Y;
Indirizzi:
Nara Inst Sci & Technol, Grad Sch Mat Sci, Nara 6300101, Japan Nara Inst Sci & Technol Nara Japan 6300101 Mat Sci, Nara 6300101, Japan Kyoto Univ, Fac Med, Dept Plast & Reconstruct Surg, Kyoto 6068507, Japan Kyoto Univ Kyoto Japan 6068507 & Reconstruct Surg, Kyoto 6068507, Japan Kuraray Co Ltd, Med R&D, Okayama 7108622, Japan Kuraray Co Ltd Okayama Japan 7108622 td, Med R&D, Okayama 7108622, Japan Kuraray Co Ltd, R&D Dept, Okayama 7050025, Japan Kuraray Co Ltd Okayama Japan 7050025 d, R&D Dept, Okayama 7050025, Japan
Titolo Testata:
JOURNAL OF PHARMACEUTICAL SCIENCES
fascicolo: 5, volume: 88, anno: 1999,
pagine: 510 - 514
SICI:
0022-3549(199905)88:5<510:ANMIDR>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
DELIVERY; AMINOPEPTIDASE; PROTEINASE; RESISTANCE; THROMBIN; CANCER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Tanihara, M Naraapant Sci & Technol, Grad Sch Mat Sci, 8916-5 Takayama, Nara 6300101, J Nara Inst Sci & Technol 8916-5 Takayama Nara Japan 6300101 J
Citazione:
M. Tanihara et al., "A novel microbial infection-responsive drug release system", J PHARM SCI, 88(5), 1999, pp. 510-514

Abstract

The aim of this study was to construct a novel drug delivery system suitable for controlled release of antibiotics. There is a need for devices that release antibiotics only during microbial infection, because prophylactic or prolonged use of antibiotics leads to serious problems, such as renal andliver toxicity and the emergence of drug-resistant bacteria (e.g., meticillin-resistant Staphylococcus aureus). We found previously that Staphylococcus aureus-infected wound fluid showed high thrombin-like activity; therefore, in this study we designed an antibiotic release system triggered by thrombin activity. We synthesized an insoluble polymer-drug conjugate in which gentamicin was bound to poly(vinyl alcohol) hydrogel through a newly developed thrombin-sensitive peptide linker. The conjugate released gentamicin when it was incubated with Staphylococcus aureus-infected wound fluid, with thrombin and leucine aminopeptidase, or with human plasma and Ca2+, whereas no biologically active gentamicin was released when the conjugate was incubated with noninfected wound fluid, with leucine aminopeptidase alone, with thrombin alone, or with plasma. Furthermore, the conjugate reduced the bacterial number in an animal model of Staphylococcus aureus infection. These results demonstrated that the conjugate has sufficient specificity and excellent potential as a stimulus-responsive, controlled drug release system.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 02:00:22