Moom Sinn Aw

Biocompatible polymer coating of titania nanotube arrays for improved drug elution and osteoblast adhesion.

Bacterial infection, extensive inflammation and poor osseointegration have been identified as the major reasons for [early] orthopaedic implant failures based on titanium. Creating implants with drug-eluting properties to locally deliver drugs is an appealing way to address some of these problems. To improve properties of titanium for orthopaedic applications, this study explored the modification of titanium surfaces with titaniananotube (TNT) arrays, and approach that combines drug delivery into bone and potentially improved bone integration. A titania layer with an array of nanotube structures (∼120 nm in diameter and 50 μm in length) was synthesized on titanium surfaces by electrochemical anodization and loaded with the water-insoluble anti-inflammatory drug indomethacin. A simple dip-coating process of polymer modification formed thin biocompatible polymer films over the drug-loaded TNTs to create TNTs with predictable drug release characteristics. Two biodegradable and antibacterial polymers, chitosan and poly(lactic-co-glycolic acid), were tested for their ability to extend the drug release time of TNTs and produce favourable bone cell adhesion properties. Dependent on polymer thickness, a significant improvement in the drug release characteristics was demonstrated, with reduced burst release (from 77% to >20%) and extended overall release from 4 days to more than 30 days. Excellent osteoblast adhesion and cell proliferation on polymer-coated TNTs compared with uncoated TNTs were also observed. These results suggest that polymer-modified implants with a TNT layer are capable of delivering a drug to a bone site over an extended period and with predictable kinetics. In addition, favourable bone cell adhesion suggests that such an implant would have good biocompatibility. The described approach is broadly applicable to a wide range of drugs and implants currently used in orthopaedic practice.

A multi-drug delivery system with sequential release using titania nanotube arrays

A multi-drug delivery system with sequential release based on titania nanotube arrays and polymer micelles as drug carriers is presented. Delivery of multiple water insoluble and soluble drugs required for combined local therapy is demonstrated.

Non-eroding drug-releasing implants with ordered nanoporous and nanotubular structures: concepts for controlling drug release

To address the limitations of systemic drug delivery, localized drug delivery systems (LDDS) based on nano-engineered drug-releasing implants are recognized as a promising alternative. Nanoporous anodic alumina (NAA) and nanotubular titania (TNT) fabricated by a simple, self-ordering electrochemical process, with regard to their outstanding properties, have emerged as one of the most reliable contenders for these applications. This review highlights the development of new LDDS based on NAA and TNT, focusing on a series of strategies for controlling their drug release characteristics that are based on: modification of their nanopore/nanotube structures, altering internal chemical functionalities, controlling pore openings by biopolymer coatings and using polymeric micelles as drug nano-carriers loaded within the implants. Several new strategies on externally triggered stimuli-responsive drug release for LDDS are also reviewed, and their significance toward the development of advanced smart implants for localized therapy is discussed. Finally, the review is summarized with conclusions and future prospects in this research field.

Titania nanotube arrays for local drug delivery: recent advances and perspectives

Introduction: Titania nanotube (TNTs) arrays engineered by simple and scalable electrochemical anodization process have been extensively explored as a new nanoengineering approach to address the limitations of systemic drug administration. Due to their outstanding properties and excellent biocompatibility, TNTs arrays have been used to develop new drug-releasing implants (DRI) for emerging therapies based on localized drug delivery (DD). This review highlights the concepts of DRI based on TNTs with a focus on recent progress in their development and future perspectives towards advanced medical therapies. Areas covered: Recent progress in new strategies for controlling drug release from TNTs arrays aimed at designing TNTs-based DRI with optimized performances, including extended drug release and zero-order release kinetics and remotely activated release are described. Furthermore, significant progress in biocompatibility studies on TNTs and their outstanding properties to promote hydroxyapatite and bone cells growths and to differentiate stem cells are highlighted. Examples of ex vivo and in vivo studies of drug-loaded TNTs are shown to confirm the practical and potential applicability of TNTs-based DRI for clinical studies. Finally, selected examples of preliminary clinical applications of TNTs for bone therapy and orthopedic implants, cardiovascular stents, dentistry and cancer therapy are presented. Expert opinion: As current studies have demonstrated, TNTs are a remarkable material that could potentially revolutionize localized DD therapies, especially in areas of orthopedics and localized chemotherapy. However, more extensive ex vivo and in vivo studies should be carried out before TNTs-based DRI could become a feasible technology for real-life clinical applications. This will imply the implementation of different approaches to overcome some technical and commercial challenges.

Tuning drug loading and release properties of diatom silica microparticles by surface modifications

Diatomaceous earth (DE), or diatomite silica microparticles originated from fossilized diatoms are a potential substitute for its silica-based synthetic counterparts to address limitations in conventional drug delivery. This study presents the impact of engineered surface chemistry of DE microparticles on their drug loading and release properties. Surface modifications with four silanes, including 3-aminopropyltriethoxy silane (APTES), methoxy-poly-(ethylene-glycol)-silane (mPEG-silane), 7-octadecyltrichlorosilane (OTS), 3-(glycidyloxypropyl)trimethoxysilane (GPTMS) and two phosphonic acids, namely 2-carboxyethyl-phosphonic acid (2 CEPA) and 16-phosphono-hexadecanoic acid (16 PHA) were explored in order to tune drug loading and release characteristics of water insoluble (indomethacin) and water soluble drugs (gentamicin). Successful grafting of these functional groups with different interfacial properties was confirmed using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Thermogravimetric analysis (TGA) was applied to determine the amount of loaded drugs and UV-spectrophotometry to analyse in vitro drug release from modified DE microparticles. Differences in drug release time (13-26 days) and loading capacity (14-24%) were observed depending on functional groups on the surface of DE microparticles. It was found that hydrophilic surfaces, due to the presence of polar carboxyl, amine or hydrolyzed epoxy group, favor extended release of indomethacin, while the hydrophobic DE surface modified by organic hydrocarbons gives a better sustained release profile for gentamicin. This work demonstrates that by changing surface functionalities on DE microparticles, it is possible to tune their drug loading and release characteristics for both hydrophobic and hydrophilic drugs and therefore achieve optimal drug delivery performance.

Drug-eluting Ti wires with titania nanotube arrays for bone fixation and reduced bone infection

Current bone fixation technology which uses stainless steel wires known as Kirschner wires for fracture fixing often causes infection and reduced skeletal load resulting in implant failure. Creating new wires with drug-eluting properties to locally deliver drugs is an appealing approach to address some of these problems. This study presents the use of titanium [Ti] wires with titania nanotube [TNT] arrays formed with a drug delivery capability to design alternative bone fixation tools for orthopaedic applications. A titania layer with an array of nanotube structures was synthesised on the surface of a Ti wire by electrochemical anodisation and loaded with antibiotic (gentamicin) used as a model of bone anti-bacterial drug. Successful fabrication of TNT structures with pore diameters of approximately 170 nm and length of 70 μm is demonstrated for the first time in the form of wires. The drug release characteristics of TNT-Ti wires were evaluated, showing a two-phase release, with a burst release (37%) and a slow release with zero-order kinetics over 11 days. These results confirmed our systems ability to be applied as a drug-eluting tool for orthopaedic applications. The established biocompatibility of TNT structures, closer modulus of elasticity to natural bones and possible inclusion of desired drugs, proteins or growth factors make this system a promising alternative to replace conventional bone implants to prevent bone infection and to be used for targeted treatment of bone cancer, osteomyelitis and other orthopaedic diseases.

Silica microcapsules from diatoms as new carrier for delivery of therapeutics

AIM This study explores the use of natural silica-based porous material from diatoms, known as diatomaceous earth, as a drug carrier of therapeutics for implant- and oral-delivery applications. MATERIALS & METHODS To prove this concept, two drugs models were used and investigated: a hydrophobic (indomethacin) and hydrophilic (gentamicin). RESULTS & DISCUSSION Results show the effectiveness of diatom microcapsules for drug-delivery application, showing 14-22 wt% drug loading capacity and sustained drug release over 2 weeks. Two steps in the drug release from diatom structures were observed: the first, rapid release (over 6 h is attributed to the surface deposited drug) and the second, slow and sustained release over 2 weeks with zero order kinetics. CONCLUSION These results confirm that natural material based on diatom silica can be successfully applied as a drug carrier for both oral and implant drug-delivery applications, offering considerable potential to replace existing synthetic nanomaterials.

Drug-releasing implants: current progress, challenges and perspectives

The need for more efficient drug delivery strategies to treat resilient diseases and the rise of micro and nanotechnology have led to the development of more sophisticated drug-releasing implants with improved capabilities and performances for localised and controlled therapies. In recent years, implantable drug-releasing systems have emerged as an outstanding alternative to conventional clinical therapies. This new breed of implants has shown promising capabilities to overcome the inherent problems of conventional implants and therapies, making clinical treatments more efficient with minimal side effects. Recent clinical trials have demonstrated that this technology can improve the life of patients and increase their life expectancy. Within this context, this review is aimed at highlighting the different types and concepts of drug-releasing implants incorporating new nanomaterials and nanotechnology-based devices. Furthermore, the principles on which these drug-releasing implants are based as well as their advantages and limitations are discussed in detail. Finally, we provide a future perspective in the development of implantable clinical drug-delivery systems based on micro and nanotechnology.

Advanced biopolymer-coated drug-releasing titania nanotubes (TNTs) implants with simultaneously enhanced osteoblast adhesion and antibacterial properties.

Here, we report on the development of advanced biopolymer-coated drug-releasing implants based on titanium (Ti) featuring titania nanotubes (TNTs) on its surface. These TNT arrays were fabricated on the Ti surface by electrochemical anodization, followed by the loading and release of a model antibiotic drug, gentamicin. The osteoblastic adhesion and antibacterial properties of these TNT-Ti samples are significantly improved by loading antibacterial payloads inside the nanotubes and modifying their surface with two biopolymer coatings (PLGA and chitosan). The improved osteoblast adhesion and antibacterial properties of these drug-releasing TNT-Ti samples are confirmed by the adhesion and proliferation studies of osteoblasts and model Gram-positive bacteria (Staphylococcus epidermidis). The adhesion of these cells on TNT-Ti samples is monitored by fluorescence and scanning electron microscopies. Results reveal the ability of these biopolymer-coated drug-releasing TNT-Ti substrates to promote osteoblast adhesion and proliferation, while effectively preventing bacterial colonization by impeding their proliferation and biofilm formation. The proposed approach could overcome inherent problems associated with bacterial infections on Ti-based implants, simultaneously enabling the development of orthopedic implants with enhanced and synergistic antibacterial functionalities and bone cell promotion.

Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain

The blood–brain barrier (BBB) blocks the passage of active molecules from the blood which makes drug delivery to the brain a challenging problem. Oral drug delivery using chemically modified drugs to enhance their transport properties or remove the blocking of drug transport across the BBB is explored as a common approach to address these problems, but with limited success. Local delivery of drugs directly to the brain interstitium using implants such as polymeric wafers, gels, and catheters has been recognized as a promising alternative particularly for the treatment of brain cancer (glioma) and neurodegenerative disorders. The aim of this study was to introduce a new solution by engineering a drug-releasing implant for local drug delivery in the brain, based on titanium (Ti) wires with titania nanotube (TNT) arrays on their surfaces. Drug loading and drug release characteristics of this system were explored using two drugs commonly used in oral brain therapy: dopamine (DOPA), a neurotransmitter agent; and doxorubicin (DOXO), an anticancer drug. Results showed that TNT/Ti wires could provide a considerable amount of drugs (>170 μg to 1000 μg) with desirable release kinetics and controllable release time (1 to several weeks) and proved their feasibility for use as drug-releasing implants for local drug delivery in the brain. Purpose In this report, a new drug-releasing platform in the form of nanoengineered Ti wires with TNT arrays is proposed as an alternative for local delivery of chemotherapeutics in the brain to bypass the BBB. To prove this concept, drug loading and release characteristics of two drugs important for brain therapy (the neurotransmitter DOPA and the anticancer drug DOXO) were explored. Methods Titania nanotube arrays on the surface of Ti wires (TNT/Ti) were fabricated using a simple anodization process, followed by separate loading of two drugs (DOPA and DOXO) inside the nanotube structures. The loading and in vitro release characteristics of prepared TNT/Ti implants were examined using thermogravimetric analysis (TGA) UV-Vis spectroscopy. Results Scanning electron microscopy studies confirmed that well-ordered, vertically aligned, densely packed nanotube arrays with an average diameter of 170 nm and length 70 μm were formed on the surface of TNT/Ti wires. TGA results showed a total drug loading of 170 μg and 1200 μg inside the TNTs for DOPA and DOXO respectively. Two-phase drug release behavior was observed including a fast release (burst) for the first 6 hours and a prolonged slow release phase for 8 days, both with acceptable dosage and desirable release kinetics. The physical, structural, loading and release characteristics of prepared TNT/Ti implants showed several advantages in comparison with existing and clinically proved brain implants. Conclusion Our results confirmed that TNT/Ti wires can be successfully employed as a suitable platform to release neurotransmitters such as DOPA and anticancer drugs such as DOXO. Hence, they are a feasible alternative as drug-releasing implants for local drug delivery in the brain to combat neurodegenerative disorders or brain tumors.