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Sol-gel silica controlled release thin films for the inhibition of methicillin-resistant Staphylococcus aureus.
Biomaterials. 2014 Jan; 35(1):509-17.B

Abstract

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection has significantly increased. Generally, the success of this bacterium as a pathogen is attributed to its ability to adhere to surfaces and remain there, under the protection of an extracellular matrix known as biofilm. To combat MRSA with regular doses of vancomycin, efforts are continuously underway to increase its effectiveness. A promising technique is to use combinational therapeutics. In vitro experiments showed that farnesol can be used as an adjuvant with conventional antibiotics. Farnesol is a natural sesquiterpenoid and quorum-sensing molecule. The biggest obstacle to using this concept is that farnesol is highly water insoluble. This compromises its bioavailability if it were to be used along with vancomycin at the site of infection when the treatment needs to be administered in vivo. Herein we designed an efficient therapeutic strategy for the simultaneous delivery of both antibiotic and adjuvant in order to treat MRSA infections. We demonstrate that sufficient quantities of both vancomycin and farnesol can be incorporated into sol-gel silica applied as thin films on an implant surface. The incorporation of the hydrophobic farnesol does not affect the stability of the thin films and neither does it affect the controlled release of vancomycin. The data demonstrate the potent adjuvant effect of farnesol on vancomycin in inhibiting MRSA infection. In vitro experiments show the complete inhibition (10(6) fold reduction in growth compared to control) of methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) when the ratio of vancomycin to farnesol in the sol-gel silica films is optimized. The local delivery of antibiotics minimizes the need for systemic antibiotics. The incorporation of vancomycin and farnesol into thin sol-gel films represents a new treatment paradigm for the topical delivery of antibiotics with adjuvant. The potential clinical benefits are significant and include avoiding the need for revision surgery, preventing surgical site infection and controlling healthcare costs.

Authors+Show Affiliations

Center for Bioactive Materials and Tissue Engineering, Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

24099711

Citation

Bhattacharyya, Sanjib, et al. "Sol-gel Silica Controlled Release Thin Films for the Inhibition of Methicillin-resistant Staphylococcus Aureus." Biomaterials, vol. 35, no. 1, 2014, pp. 509-17.
Bhattacharyya S, Agrawal A, Knabe C, et al. Sol-gel silica controlled release thin films for the inhibition of methicillin-resistant Staphylococcus aureus. Biomaterials. 2014;35(1):509-17.
Bhattacharyya, S., Agrawal, A., Knabe, C., & Ducheyne, P. (2014). Sol-gel silica controlled release thin films for the inhibition of methicillin-resistant Staphylococcus aureus. Biomaterials, 35(1), 509-17. https://doi.org/10.1016/j.biomaterials.2013.09.073
Bhattacharyya S, et al. Sol-gel Silica Controlled Release Thin Films for the Inhibition of Methicillin-resistant Staphylococcus Aureus. Biomaterials. 2014;35(1):509-17. PubMed PMID: 24099711.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sol-gel silica controlled release thin films for the inhibition of methicillin-resistant Staphylococcus aureus. AU - Bhattacharyya,Sanjib, AU - Agrawal,Ashwin, AU - Knabe,Christine, AU - Ducheyne,Paul, Y1 - 2013/10/05/ PY - 2013/06/18/received PY - 2013/09/23/accepted PY - 2013/10/9/entrez PY - 2013/10/9/pubmed PY - 2014/7/8/medline KW - Antibiotics KW - Controlled release KW - Drug delivery KW - Implant KW - MRSA KW - Sol–gel silica SP - 509 EP - 17 JF - Biomaterials JO - Biomaterials VL - 35 IS - 1 N2 - The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection has significantly increased. Generally, the success of this bacterium as a pathogen is attributed to its ability to adhere to surfaces and remain there, under the protection of an extracellular matrix known as biofilm. To combat MRSA with regular doses of vancomycin, efforts are continuously underway to increase its effectiveness. A promising technique is to use combinational therapeutics. In vitro experiments showed that farnesol can be used as an adjuvant with conventional antibiotics. Farnesol is a natural sesquiterpenoid and quorum-sensing molecule. The biggest obstacle to using this concept is that farnesol is highly water insoluble. This compromises its bioavailability if it were to be used along with vancomycin at the site of infection when the treatment needs to be administered in vivo. Herein we designed an efficient therapeutic strategy for the simultaneous delivery of both antibiotic and adjuvant in order to treat MRSA infections. We demonstrate that sufficient quantities of both vancomycin and farnesol can be incorporated into sol-gel silica applied as thin films on an implant surface. The incorporation of the hydrophobic farnesol does not affect the stability of the thin films and neither does it affect the controlled release of vancomycin. The data demonstrate the potent adjuvant effect of farnesol on vancomycin in inhibiting MRSA infection. In vitro experiments show the complete inhibition (10(6) fold reduction in growth compared to control) of methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) when the ratio of vancomycin to farnesol in the sol-gel silica films is optimized. The local delivery of antibiotics minimizes the need for systemic antibiotics. The incorporation of vancomycin and farnesol into thin sol-gel films represents a new treatment paradigm for the topical delivery of antibiotics with adjuvant. The potential clinical benefits are significant and include avoiding the need for revision surgery, preventing surgical site infection and controlling healthcare costs. SN - 1878-5905 UR - https://www.unboundmedicine.com/medline/citation/24099711/Sol_gel_silica_controlled_release_thin_films_for_the_inhibition_of_methicillin_resistant_Staphylococcus_aureus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0142-9612(13)01173-3 DB - PRIME DP - Unbound Medicine ER -