Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Feb 15:11:661-73.
doi: 10.2147/IJN.S95885. eCollection 2016.

Development of nanoantibiotic delivery system using cockle shell-derived aragonite nanoparticles for treatment of osteomyelitis

Affiliations

Development of nanoantibiotic delivery system using cockle shell-derived aragonite nanoparticles for treatment of osteomyelitis

Lamin Saidykhan et al. Int J Nanomedicine. .

Abstract

A local antibiotic delivery system (LADS) with biodegradable drug vehicles is recognized as the most effective therapeutic approach for the treatment of osteomyelitis. However, the design of a biodegradable LADS with high therapeutic efficacy is too costly and demanding. In this research, a low-cost, facile method was used to design vancomycin-loaded aragonite nanoparticles (VANPs) with the aim of understanding its potency in developing a nanoantibiotic bone implant for the treatment of osteomyelitis. The aragonite nanoparticles (ANPs) were synthesized from cockle shells by a hydrothermal approach using a zwitterionic surfactant. VANPs were prepared using antibiotic ratios of several nanoparticles, and the formulation (1:4) with the highest drug-loading efficiency (54.05%) was used for physicochemical, in vitro drug release, and biological evaluation. Physiochemical characterization of VANP was performed by using transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction, and Zetasizer. No significant differences were observed between VANP and ANP in terms of size and morphology as both samples were cubic shaped with sizes of approximately 35 nm. The Fourier transform infrared spectroscopy of VANP indicated a weak noncovalent interaction between ANP and vancomycin, while the zeta potential values were slightly increased from -19.4±3.3 to -21.2±5.7 mV after vancomycin loading. VANP displayed 120 hours (5 days) release profile of vancomycin that exhibited high antibacterial effect against methicillin-resistant Staphylococcus aureus ATCC 29213. The cell proliferation assay showed 80% cell viability of human fetal osteoblast cell line 1.19 treated with the highest concentration of VANP (250 µg/mL), indicating good biocompatibility of VANP. In summary, VANP is a potential formulation for the development of an LADS against osteomyelitis with optimal antibacterial efficacy, good bone resorbability, and biocompatibility.

Keywords: antibacterial activity; biocompatibility; cockle shell-derived nanoparticles; in vitro drug release; nanoantibiotics.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Structural formula of vancomycin. Notes: Reprinted from Structure, 1996;4(12), Schäfer M, Schneider TR, Sheldrick GM, Crystal structure of vancomycin, pages 1509–1515, Copyright © 1996 Elsevier Science Ltd, with permission from Elsevier.
Figure 2
Figure 2
The FT-IR spectra of (A) free vancomycin, (B) ANP, and (C) VANP. Note: All the peaks of vancomycin and naked ANP present in the FT-IR spectra of VANP are possibly due to the interaction between the vancomycin and ANP. Abbreviations: FT-IR, Fourier transform infrared; ANP, aragonite nanoparticle; VANP, vancomycin-loaded aragonite nanoparticle.
Figure 3
Figure 3
X-ray diffraction patterns of (A) vancomycin, (B) naked ANP, and (C) VANP. Note: The XRD patterns of VANPs were very much similar to the naked nanoparticles. Abbreviations: ANP, aragonite nanoparticle; VANP, vancomycin-loaded aragonite nanoparticle; XRD, X-ray powder diffraction.
Figure 4
Figure 4
TEM images of pure aragonite nanoparticles from cockle shells before (A) and after (B) loading with vancomycin. Abbreviation: TEM, transmission electron microscopy.
Figure 5
Figure 5
Particle size distribution of pure aragonite nanoparticles from cockle shells (ANP) before (A) and after (B) loading with vancomycin (VANP). Note: The size distribution obtained from random measurement of at least 100 nanoparticles revealed 34±5 and 36±6 nm as the average diameters of ANP and VANP, respectively. Abbreviations: ANP, aragonite nanoparticle; VANP, vancomycin-loaded aragonite nanoparticle.
Figure 6
Figure 6
Release profile of vancomycin from VANP. Notes: The initial release relatively occurred at a rapid rate of 15 hours followed by a relatively slow and sustained release rate for 120 hours (day 5). The results obtained from three data values were presented as mean ± SD, n=3. Abbreviations: VANP, vancomycin-loaded aragonite nanoparticle; SD, standard deviation.
Figure 7
Figure 7
Antibacterial effect of vancomycin released from VANP against MRSA ATCC 29213 based on the diameter of the inhibition zone. Note: The release samples (from 1 to 96 hr [4 days]) expressed the inhibition of bacterial growth, which is indicated by the clear zones around the wells containing the samples. Abbreviations: VANP, vancomycin-loaded aragonite nanoparticle; MRSA, methicillin-resistant Staphylococcus aureus; ATCC, American Type Culture Collection; hr, hour/s.
Figure 8
Figure 8
Trend of susceptibility of released vancomycin against MRSA ATCC 29213. Notes: The release samples from 1 to 96 hours (4 days) expressed antibacterial effect with a decreasing trend of susceptibility. The results obtained from three data values were presented as mean ± SD, n=3. Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; ATCC, American Type Culture Collection; SD, standard deviation.
Figure 9
Figure 9
Comparison of cumulative released concentration of vancomycin determined by a UV spectrophotometer and microbiological (agar-dilution) assay, respectively. Notes: Both spectrophotometric and microbiological concentration curves exhibited a similar trend. The results are expressed as the mean ± SD, n=3, of data from three similar concentration values. Abbreviations: UV, ultraviolet; SD, standard deviation.
Figure 10
Figure 10
Microbiological concentration of released vancomycin (responsible for bacterial growth inhibition) as a function of release time. Note: The experimental results are presented as mean ± SD, n=2, of data obtained from two independent experiments that yielded similar results. Abbreviations: SD, standard deviation; VANP, vancomycin-loaded aragonite nanoparticle.
Figure 11
Figure 11
In vitro growth response of osteoblast (hFOB 1.19) cell to vancomycin, cockle shell-based ANP, and VANP as a measure of cytotoxicity. Note: Data are reported as the mean ± SD, n=3, based on three independent experiments. Abbreviations: hFOB 1.19, human fetal osteoblast cell line 1.19; ANP, aragonite nanoparticle; VANP, vancomycin-loaded aragonite nanoparticle; SD, standard deviation.

References

    1. Kundu B, Soundrapandian C, Nandi SK, et al. Development of new localized drug delivery system based on ceftriaxone-sulbactam composite drug impregnated porous hydroxyapatite: a systematic approach for in vitro and in vivo animal trial. Pharm Res. 2010;27(8):1659–1676. - PubMed
    1. Tsourvakas S. Local Antibiotic Therapy in the Treatment of Bone and Soft Tissue Infections. 2012. [Accessed December 24, 2015]. Available from: http://cdn.intechopen.com/pdfs-wm/26559.pdf.
    1. Kishner S. Osteomyelitis Treatment & Management. Medscape; 2012. [Accessed December 24, 2015]. Available from: http://emedicine.medscape.com/article/1348767-treatment.
    1. Gogia JS, Meehan JP, Di Cesare PE, et al. Local antibiotic therapy in osteomyelitis. Semin Plast Surg. 2009;1(212):100–107. - PMC - PubMed
    1. Valle GA, Gautier H, Gaudin A, et al. Complete Healing of Severe Experimental Osseous Infections Using a Calcium-Deficient Apatite as a Drug-Delivery System. In: Pignatello R, editor. Biomaterials Applications for Nanomedicine. Rijeka, Croatia: InTech; 2011. [Accessed December 24, 2015]. Available from: http://www.intechopen.com/books/biomaterials-applications-for-nanomedici....

Publication types

MeSH terms