Well-ordered mesoporous bioactive glasses (MBG): A promising bioactive drug delivery system

doi:10.1016/j.jconrel.2005.11.002

Journal of Controlled Release

Volume 110, Issue 3, 21 February 2006, Pages 522-530

https://doi.org/10.1016/j.jconrel.2005.11.002 Get rights and content

Abstract

The local drug release system is considered to be an alternative to treat the bone infection. In this paper, well-ordered mesoporous bioactive glasses (MBG) with high specific surface area have been synthesized in aqueous solution by a two-step acid-catalyzed self-assembly process combined with hydrothermal treatment. Gentamicin was encapsulated into the MBG by adsorption method and in vitro release of gentamicin from MBG was performed in distilled water and modified simulated body fluid (SBF), respectively. The results showed that the amount of drug loading of MBG was three times more than that of conventional sol-gel 58S. The outcomes of drug release in distilled water and in SBF showed that M58S effectively decreased the initial burst. During the release period, gentamicin was released from the M58S at a much lower release rate as compared to that from 58S after soaking in distilled water and SBF. Furthermore, the drug release was sensitive to the pH and ionic concentration of the release medium suggesting possible controls of the release rate. In addition, in contrast to conventional sol-gel 58S, M58S had higher ability to induce hydroxyapatite (HAp) formation. Therefore, well-ordered mesoporous bioactive glasses might be used as a bioactive drug release system for preparation of bone implant materials.

Introduction

Study and development of biomaterials for bone filling and replacement is one of the most important fields in orthopedic surgery. Some bioactive materials, such as hydroxyapatite, bioactive glasses, and bioceramics, could spontaneously bond to living bone in the body without fibrous tissue forming around them [1], [2], [3]. These materials could facilitate integration of osseous tissue with the implant, promoting the bone regeneration and successful cure of the osseous tissue. However, the risk of bone infection is a serious trouble associated with bone filling and replacement. High osteomyelitis incidence carries bone necrosis as well as a relatively high mortality [4].

Techniques for the treatment including systemic antibiotic administration, surgical debridement, wound drainage, and implant removal have been applied in order to prevent further complication, such as loss of function and septicemia [5]. However, all of these treatments give the patients extra suffering. In addition, conventional drug delivery modes, such as injection of a dose or taking of a pill, still exhibit some drawbacks. When drugs are taken, the drug concentration in blood rises dramatically up to peaks and then declines [6]. Therefore many drugs exhibit toxic at peaks and ineffective below the minimum effective plasma drug levels. Moreover, special drugs treat special diseases and injure other tissues.

The controlled drug release has been attractive to many pharmaceutical scientists as well as chemists and materials scientists due to high delivery efficiency, continuous action, reduced toxicity and convenience to the patients. At present, the studies on controlled drug delivery systems mainly focus on biopolymers [7], [8], [9], [10], [11]. However, they may not be suitable for bone repair as filling materials since most of the biopolymers are not able to chemically bond to living bone.

Mesoporous silica with high specific surface area, well-ordered pores, and large pore volumes has been addressed to be a potential controlled drug delivery system. MCM-41 [12], [13] and SBA-15 [14] have been investigated as drug delivery systems and showed a controlled release characteristic. The drug molecules can be hosted within the mesopores by immersion techniques and released via a diffusion-based mechanism without drug–silica interaction [12]. The adjustable pore diameters and well-ordered mesoporous structure are expected to facilitate the free administration of drug release pattern [6]. However, mesoporous silica also may not be suitable for bone repair as filling materials since it lacks bioactivity [15]. Recently, Yan et al. have synthesized highly ordered mesoporous bioactive glasses (MBG) [16], which showed higher bioactivity than conventional sol-gel bioactive glasses. Considering the well-ordered mesoporous structure and superior in vitro bioactivity, MBG may be a promising material for bone defect filling. However, there is no report on the drug release property of well-ordered mesoporous bioactive glasses.

The purpose of the present study was to investigate the drug release property of MBG. The well-ordered mesoporous bioactive glasses were synthesized by a novel method. The gentamicin sulfate (GS), a wide spectrum antibiotic treating osteomyelitis, was chosen and encapsulated into the MBG to obtain a drug delivery system.

Section snippets

Materials

Tetraethyl orthosilicate (TEOS), Trithyl phosphate (TEP) and Ca(NO₃)₂·4H₂O were purchased from LINGFENG Co. (China). Surfactant pluronic P123 (EO₂₀–PO₇₀–EO₂₀) was purchased from JIDA Co. (China). The antibiotic gentamicin sulfate (GS, powder) was purchased from PUKANG Co. (China).

Preparation of mesoporous bioactive glasses (MBG)

MBG was synthesized by a two-step acid-catalyzed self-assembly process combined with hydrothermal treatment in an inorganic–organic system [17], and the chemical composition was the same as the traditional sol-gel

Characterization of MBG

The small-angle powder X-ray diffraction (SAXRD) patterns (Fig. 1) of as-synthesized and calcined M58S powders show three well-resolved peaks that are indexable as (100), (110), (200) reflections associated with p6mm hexagonal symmetry, which indicate the existence of a high degree of hexagonal mesoscopic organization [17]. The cell parameters are 11.8 and 10.9 nm for as-synthesized and calcined M58S, respectively. The nitrogen sorption isotherm (Fig. 2) of the calcined sample is type IV with

Discussion

The results of N₂ adsorption and drug loading indicated that the ability of drug loading was in a close relationship with the specific surface area and pore volume of materials. The MBG was just like a reservoir. With the increase of pore volume, the amount of drug loaded for MBG increased proportionately. The dimension of gentamicin was 0.52 × 1.53 nm² [14], which was much smaller than the pore diameter of M58S and M77S, and could entirely be hosted into the MBG, which explained the higher drug

Conclusions

In this work, a novel bioactive drug delivery system, well-ordered mesoporous bioactive glass, has been synthesized and the release behavior of controlled drug release from this system was carefully studied. The results showed that the amount of drug loading was greatly influenced by the well-ordered mesostructure, and the amount of drug loading of MBG was three times more than that of conventional 58S. During whole release period, gentamicin was released from the M58S and M77S at a much lower

Acknowledgement

This work was financially supported by the National Basic Science Research Program of China (973 Program) (Grant No: 2005CB522700) and the Science and Technology Commission of Shanghai Municipality (Grant No: 02JC14009 and 05DJ14005).

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Well-ordered mesoporous bioactive glasses (MBG): A promising bioactive drug delivery system

Abstract

Introduction

Section snippets

Materials

Preparation of mesoporous bioactive glasses (MBG)

Characterization of MBG

Discussion

Conclusions

Acknowledgement

J. Control. Release

J. Control. Release

Adv. Drug Deliv. Rev.

J. Control. Release

Solid State Sci.

J. Pharm. Sci.

Biomaterials

Bonding mechanisms at the interface of ceramic prosthetic materials

J. Biomed. Mater. Res.

Bioceramics: from concept to clinic

J. Am. Ceram. Soc.

Glasses with application

Eur. J. Inorg. Chem.

Pathophysiology of chronic bacterial osteomyelitis. Why do antibiotics fail so often?

Postgrad. Med.

Infected prostheses: the role of antibiotic cement