Review
Ordered mesoporous materials for drug delivery

https://doi.org/10.1016/j.micromeso.2008.07.002Get rights and content

Abstract

In recent years, mesoporous materials, which have unique pore size, higher surface area and pore volume, have been widely employed as carriers for controlled drug delivery. Compared with amorphous colloidal and porous silica, mesoporous silicas exhibit higher loading of drugs and provide a controlled drug release if modified by functionalisation. In this paper, we review the research work in this area discussing the textural and structural properties of several mesoporous materials such as M41S, SBA, MSU, and HMS in drug loading and release profile. The influence of functionalisation of mesoporous materials by organics is also discussed. Two systems of drug delivery mechanism, sustained release and stimuli-responsive controlled-release, are compared and drug release kinetics is described. Bioactivity of various mesoporous solids is also presented.

Introduction

Over the past three decades, there has been rapid growth in the area of drug delivery, in searching of new drug delivery systems (NDDS). Both natural and synthetic materials have been tested and proposed as components of NDDS and many efforts have been made to synthesise materials with the biological, technological, and mechanical properties “ad hoc” for each application in drug delivery [1]. In recent years, many types of materials including inorganic silica, carbon materials and layered double hydroxides [2], [3], [4] as well as polymeric [5], [6], [7] matrix have been employed as substrates for drug delivery. Amorphous colloidal and porous silica has been proposed as a drug delivery system on the basis of silica-embedding and biocompatibility [8]. In silica-based systems, drugs are known to be adsorbed on commercially available silica. However, direct mixture of both silica sol and the drug results often in heterogeneous dispersion of drug through the gel, which can affect the release rate of the drug between different samples [9]. Controlled drug delivery systems can achieve precisely spatial and temporal delivery of therapeutic agents to the target site. Generally, the controlled drug delivery systems can maintain the concentration of drugs in the precise sites of the body within the optimum range and under the toxicity threshold, which improve the therapeutic efficacy and reduce toxicity. In the past years, controlled drug delivery has been developed in polymer-based system and also novel inorganic materials-based systems [10].

For a controlled-release drug delivery system biodegradability and biocompatibility are the fundamental requirements [11]. Studies reported in recent years have shown that some crosslinked chitosan microspheres are cytotoxic and may impair the biocompatibility of crosslinked materials. Owing to high chemical and thermal stabilities, large surface areas and good compatibilities with other materials, porous silica has also found wide application in adsorption, enzyme immobilisation and drug delivery. The new developed sol–gel technology offers the possibilities for incorporating biologically active agents within silica gel and for controlling their release kinetics from the gel matrix [12].

Since the discovery of ordered mesoporous silica materials in 1990s, synthesis and applications of mesoporous solids have received intensive attention due to their highly ordered structures, larger pore size, and high surface area. In the past decade, mesoporous materials have found a lot of applications in separation, catalysis, sensors and devices [13], [14]. Due to stable mesoporous structure and well-defined surface properties, mesoporous materials seem ideal for encapsulation of pharmaceutical drug, proteins and other biogenic molecules. In recent years, employing mesoporous materials for hosting and further delivering of a variety of molecules of pharmaceutical interest has been appeared [15], [16]. It has been shown that both small and large molecular drugs can be entrapped within the mesopores by an impregnation process and liberated via a diffusion-controlled mechanism. Table 1 presents the porous structure of some mesoporous materials, which have been employed for drug delivery.

Since the report by Vallet-Regi et al. in 2001 using MCM-41 as a new drug delivery system [2], a lot of investigations have been done in this area, developing different types of mesoporous materials with varying porous structure and functionality for sustained drug released and stimuli-responsive release. Here, we review the progress of this novel application of mesoporous materials as carriers for various drug delivery, comparing the different behaviour of drug/mesoporous-solid systems. We concentrate on the important factors influencing the drug loading and release mode as well as the release kinetics. We also discuss the biocompatibility of the drug systems and their emerging application for tissue engineering.

Section snippets

Drug/mesoporous-silica systems for sustained release of various drugs

The definition of drug delivery system can be of a system that is capable of releasing a carried bioactive agent in a specific location at a specific rate. The main aim of this type of system is to facilitate the dosage and duration of the drug effect, the minimal harm to the patient and improving human health, since they allow for the reduction of the dosage frequency [18].

MCM-41 as one of the importantly synthesised mesoporous materials, M41S [19], has been firstly employed as drug delivery

Drug release profile and the kinetics

Several issues are of interest regarding this new property of mesoporous materials and all of them point to the possibility of gaining control over the releasing pattern of the guest drug, a critical parameter for clinical applications. Several factors could affect the release profile of the hosted molecule, the nature of the host–guest chemical interaction and the pore size of the matrix among them.

Stimuli-responsive control release system

Compared with the sustained release system, the stimuli-responsive controlled-release system can achieve a site-selective, controlled-release pattern, which can improve the therapeutic efficacy. For traditional responsive polymer/drug systems, degradable polymers are synthesised in the presence of the drug molecule of interest. The resulting polymer/drug composite materials usually exhibit slow rates of spontaneous drug release. Upon stimulation, the degradation of the polymer matrix is

Biocompatibility of mesoporous silica/drug system

A variety of synthetic and natural polymers have been employed as controlled-release drug delivery systems for humans. Biodegradability and biocompatibility are the fundamental requirements that determine the possible therapeutic and surgical applications of a polymeric biomaterial. For mesoporous silica-based drug system, bioactivity is also an important issue for its potential application. Gomez-Vega et al. first investigated the bioactivity of mesoporous silica films coated on Ti6Al4V. When

Summary and perspectives

It has been shown that ordered mesoporous silica with stable mesoporous structure, large surface area, good biocompatibility and tailored size of mesopores and functionalisation has exhibited promising application as controlled drug delivery system. The mesoporous silica demonstrates higher drug loading and controlled sustained release as well as responsive release under certain external stimuli such as light, magnetite, chemical, pH and temperature. Among various mesoporous silicas, HMS silica

References (65)

  • J.K. Oh et al.

    Prog. Polym. Sci.

    (2008)
  • M. Sokolsky-Papkov et al.

    Adv. Drug Deliv. Rev.

    (2007)
  • J. Watanabe et al.

    Colloi. Surf. B-Biointerfaces

    (2005)
  • Z.Z. Li et al.

    J. Control Release

    (2004)
  • A. Taguchi et al.

    Micropor. Mesopor. Mat.

    (2005)
  • P.B. Malafaya et al.

    Curr. Opin. Solid St. Mater.

    (2002)
  • P. Horcajada et al.

    Micropor. Mesopor. Mat.

    (2004)
  • I. Izquierdo-Barba et al.

    Eur. J. Pharm. Sci.

    (2005)
  • W. Zeng et al.

    Mater. Res. Bull.

    (2005)
  • A.L. Doadrio et al.

    J. Control Release

    (2004)
  • M. Vallet-Regi et al.

    Solid State Ionics

    (2004)
  • V. Zelenak et al.

    Micropor. Mesopor. Mat.

    (2005)
  • Y.F. Zhu et al.

    Turret Mat.

    (2005)
  • W. Zeng et al.

    Mat. Chem. Phys.

    (2006)
  • Y.F. Zhu et al.

    Turret Mat.

    (2005)
  • J. Andersson et al.

    Biomaterials

    (2005)
  • I. Izquierdo-Barba et al.

    Solid State Sci.

    (2005)
  • M. Vallet-Regi et al.

    Solid State Sci.

    (2005)
  • B. Onida et al.

    Stud. Sur. Sci. Catal.

    (2005)
  • W. Xia et al.

    J. Control Release

    (2006)
  • G. Cavallaro et al.

    Drug Deliv.

    (2004)
  • M. Vallet-Regi et al.

    Chem. Mater.

    (2001)
  • P.X. Zhi et al.

    Chem. Eng. Sci.

    (2006)
  • M. Vallet-Regi

    Chem. Europ. J.

    (2006)
  • J. Varshosaz

    Expert Opin. Drug Deliv.

    (2007)
  • C. Barbe et al.

    Adv. Mater.

    (2004)
  • C. Tourne-Peteilh et al.

    New. J. Chem.

    (2003)
  • Q. Yang et al.

    Chem. Mater.

    (2005)
  • B.J. Scott et al.

    Chem. Mater.

    (2001)
  • M. Hartmann

    Chem. Mater.

    (2005)
  • H.H.P. Yiu et al.

    J. Mater. Chem.

    (2005)
  • P. Selvam et al.

    Ind. Eng. Chem. Res.

    (2001)
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