Search

Abstract Advances in molecular biology and nanomedicine based therapies hold promise to obviate the need of multiple surgical interventions (associated with current management) in craniosynostosis by preventing bone re-ossification. One such adjunctive therapy involves application of glypicans 1 and 3 (GPC1 and GPC3) that are BMP inhibitors implicated in downregulating the BMP2 activity in prematurely fusing sutures. Electrochemically anodized Titania nanotube (TNT) arrays have been recognized as a promising localized, long-term drug delivery platform for bone-related therapies. This study presents the application of nanoengineered TNT/Ti implants loaded with recombinant glypicans for craniosynostosis therapy. By using Dual luciferase Reporter assay, we tested the biofunctionality of eluted glypicans from the TNT/Ti implants for BMP2 bioactivity regulation in C2C12 murine myoblast cell line. BMP2 activity was inhibited significantly for up to 15 days by the glypicans released from polymer-coated TNT/Ti implants, indicating their potential application in adjunctive craniosynostosis treatment. Graphical Abstract Titania nanotube- based protein delivery implants have been assessed in vitro to provide a sustained release of bone inhibiting glypicans (rGPC1 and rGPC3). The bioactivity of released glypicans was confirmed by downregulation of BMP2 expression in transfected C2C12 cells. Image 1 Highlights • Titania nanotubes (TNTs) implants have been engineered by electrochemical process. • TNTs glypican releasing implants have been prepared and evaluated. • BMP2 activity was inhibited significantly for up to 15 days by these implants. • The potential for craniosynostosis therapy is proposed by this approach. [ABSTRACT FROM AUTHOR]

Gene-silencing miRNA and siRNA are emerging as attractive therapeutics with potential to suppress any genes, which could be especially useful in combination cancer therapy to overcome multidrug resistant (MDR) cancer. Nanomedicine aims to advance cancer treatment through functional nanocarriers that delivers one or more therapeutics to cancer tissue and cells with minimal off-target effects and suitable release kinetics and dosages. Although much effort has gone into developing circulating nanocarriers with targeting functionality for systemic administration, another alternative and straightforward approach is to utilize formulations to be administered directly to the site of action, such as pulmonary and intratumoral delivery. The combination of gene-silencing RNA with drugs in nanocarriers for localized delivery is emerging with promising results. In this review, the current progress and strategies for local co-administration of RNA and drug for synergistic effects and future potential in cancer treatment are presented and discussed. Key advances in RNA-drug anticancer synergy and localized delivery systems were combined with a review of the available literature on local co-administration of RNA and drug for cancer treatment. It is concluded that advanced delivery systems for local administration of gene-silencing RNA and drug hold potential in treatment of cancer, depending on indication. In particular, there are promising developments using pulmonary delivery and intratumoral delivery in murine models, but further research should be conducted on other local administration strategies, designs that achieve effective intracellular delivery and maximize synergy and feasibility for clinical use. [ABSTRACT FROM AUTHOR]

The organic modification of three-dimensional porous diatom frustules (biosilica) and their fossils (diatomite) is promising in heavy metal adsorption. However, the preparation of such materials involves complex processes, high costs, and environmental hazards. In this study, organic-biosilica composites based on in situ self-modification of diatoms were prepared by freeze-drying pretreatment. Freeze-drying resulted in the release of the intercellular organic components of diatoms, followed by loading on the surface of their diatom frustules. The bio-adsorbent exhibits outstanding Cd2+ adsorption capacity (up to 220.3 mg/g). The adsorption isotherms fitted the Langmuir model and the maximum adsorption capacity was 4 times greater than that of diatom biosilica (54.1 mg/g). The adsorption kinetics of Cd2+ was adequately described by a pseudo-second-order model and reached equilibrium within 30 min. By combining focused ion beam thinning with transmission electron microscopy–energy dispersive X-ray spectroscopy, the internal structure of the composite and the Cd2+ distribution were investigated. The results showed that the organic matter of the composite adsorbed approximately 10 times more Cd2+ than inorganic biosilica. The adsorption mechanism was dominated by complexation between the abundant organic functional groups (amide, carboxyl, and amino groups) on the surfaces of composite and Cd2+. The bio-adsorbent was demonstrated to have wide applicability in the presence of competitive cations (Na+, K+, Ca2+, and Mg2+) and under a wide range of pH (3–10) conditions. Thus, the self-modification of diatoms offers a promising organic–inorganic composite for heavy metal remediation. [Display omitted] • Diatom-based adsorbents were prepared by in-situ modification with freeze-drying. • Diatom's organic component was released and loaded on frustule's external surface. • The adsorbent had a high adsorption capacity (220.3 mg/g) and a short equilibrium time (30 min). • FIB-TEM-EDS showed organic matter adsorbed Cd2+ ∼10 times more than biosilica. [ABSTRACT FROM AUTHOR]

Abstract: The biomedical applications of graphene-based materials, including drug delivery, have grown rapidly in the past few years. Graphene and graphene oxide have been extensively explored as some of the most promising biomaterials for biomedical applications due to their unique properties: two-dimensional planar structure, large surface area, chemical and mechanical stability, superb conductivity and good biocompatibility. These properties result in promising applications for the design of advanced drug delivery systems and delivery of a broad range of therapeutics. In this review we present an overview of recent advances in this field of research. We briefly describe current methods for the surface modification of graphene-based nanocarriers, their biocompatibility and toxicity, followed by a summary of the most appealing examples demonstrated for the delivery of anti-cancer drugs and genes. Additionally, new drug delivery concepts based on controlling mechanisms, including targeting and stimulation with pH, chemical interactions, thermal, photo- and magnetic induction, are discussed. Finally the review is summarized, with a brief conclusion of future prospects and challenges in this field. [Copyright &y& Elsevier]

Abstract: Anodic aluminium oxide (AAO) has been investigated and utilized in numerous products for almost a century. But the rapidly increasing interest in nanoscale materials and their outstanding properties has propelled nanoporous AAO to the fore as one of the most popular nanomaterial with applications across a gamut of areas including molecular separation, catalysis, energy generation and storage, electronics and photonics, sensors and biosensors, drug delivery and template synthesis. Material fabrication of AAO is based on facile and inexpensive electrochemical anodization with the self-ordering process of nanopores not requiring any lithography or templating, and the outcome of the process are perfectly ordered and size controlled nanopores with distinctive pore geometries. Recent research on AAO is characterized by a remarkable trajectory of innovation, in particular with regards to control of surface functionality and, concomitantly, to the design of intricate structural features such as modulated, branched, and multilayered pore architectures. This review illuminates research on recent development of AAO focussing on surface and structural engineering, and on emerging applications. Key examples and critical preparative issues and resulting improvements sparking opportunities for further applications in AAO properties are discussed. We conclude this review with an outlook providing a critical perspective on future trends on surface and structural engineering of AAO. [Copyright &y& Elsevier]

Abstract: A non-invasive and external stimulus-driven local drug delivery system (DDS) based on titania nanotube (TNT) arrays loaded with drug encapsulated polymeric micelles as drug carriers and ultrasound generator is described. Ultrasound waves (USW) generated by a pulsating sonication probe (Sonotrode) in phosphate buffered saline (PBS) at pH 7.2 as the medium for transmitting pressure waves, were used to release drug-loaded nano-carriers from the TNT arrays. It was demonstrated that a very rapid release in pulsatile mode can be achieved, controlled by several parameters on the ultrasonic generator. This includes pulse length, time, amplitude and power intensity. By optimization of these parameters, an immediate drug-micelles release of 100% that spans a desirable time of 5–50min was achieved. It was shown that stimulated release can be generated and reproduced at any time throughout the TNT-Ti implant life, suggesting considerable potential of this approach as a feasible and tunable ultrasound-mediated drug delivery system in situ via drug-releasing implants. It is expected that this concept can be translated from an in vitro to in vivo regime for therapeutic applications using drug-releasing implants in orthopedic and coronary stents. [Copyright &y& Elsevier]

Abstract: 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 (∼120nm in diameter and 50μm 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 4days to more than 30days. 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. [Copyright &y& Elsevier]

Diatoms are unicellular, eukaryotic, photosynthetic algae that are found in aquatic environments. Diatoms have enormous ecological importance on this planet and display a diversity of patterns and structures at the nano- to millimetre scale. Diatom nanotechnology, a new interdisciplinary area, has spawned collaborations in biology, biochemistry, biotechnology, physics, chemistry, material science and engineering. We survey diatom nanotechnology since 2005, emphasizing recent advances in diatom biomineralization, biophotonics, photoluminescence, microfluidics, compustat domestication, multiscale porosity, silica sequestering of proteins, detection of trace gases, controlled drug delivery and computer design. Diatoms might become the first organisms for which the gap in our knowledge of the relationship between genotype and phenotype is closed. [Copyright &y& Elsevier]