The progressive role of acoustic cavitation for non-invasive therapies, contrast imaging and blood-tumor permeability enhancement.

Introduction: Drug delivery pertaining to acoustic cavitation generated from ultrasonic (US) irradiation is advantageous for devising smarter and more advanced therapeutics. The aim is to showcase microbubbles as drug carriers and robust theranostic for non-invasive therapies across diverse biomedical disciplines, highlighting recent technologies in this field for overcoming the blood-brain barrier (BBB) to treat cancers and neurological disorders.

Areas Covered: This article reviews work on the optimized tuning of ultrasonic parameters, sonoporation, transdermal and responsive drug delivery, acoustic cavitation in vasculature and oncology, contrast imaging for real-time magnification of cell-microbubble dynamics and biomolecular targeting.

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).

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.

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.

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.

Radiofrequency-triggered release for on-demand delivery of therapeutics from titania nanotube drug-eluting implants.

Aim: This study aimed to demonstrate radiofrequency (RF)-triggered release of drugs and drug carriers from drug-eluting implants using gold nanoparticles as energy transducers.

Materials & Methods: Titanium wire with a titania nanotube layer was used as an implant loaded with indomethacin and micelles (tocopheryl PEG succinate) as a drug and drug carrier model. RF signals were generated from a customized RF generator to trigger in vitro release.

Polymeric micelles for multidrug delivery and combination therapy.

The use of conventional therapy based on a single therapeutic agent is not optimal to treat human diseases. The concept called "combination therapy", based on simultaneous administration of multiple therapeutics is recognized as a more efficient solution. Interestingly, this concept has been in use since ancient times in traditional herbal remedies with drug combinations, despite mechanisms of these therapeutics not fully comprehended by scientists.

Ultrasound enhanced release of therapeutics from drug-releasing implants based on titania nanotube arrays.

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.

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).

Characterization of drug-release kinetics in trabecular bone from titania nanotube implants.

Purpose: The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti) wires generated with titania nanotube (TNT) arrays as drug-releasing implants for local drug delivery

Methods: Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B) was used as the model drug, loaded inside the TNT-Ti implants, to monitor drug release and transport in trabecular bone.

Local drug delivery to the bone by drug-releasing implants: perspectives of nano-engineered titania nanotube arrays.

Titania nanotube (TNT) arrays fabricated by electrochemical anodization of titanium are currently one of the most attractive nanomaterials due to their remarkable properties. In this review, we highlight recent research activities that are focused on the application of the TNT arrays for local drug delivery, specifically for addressing problems associated with orthopedic implants. The advantages of drug-releasing implants based on TNT arrays for local delivery of therapeutics in bone related to these challenging problems including inflammation, infection and osseointegration are discussed.

Polymer micelles for delayed release of therapeutics from drug-releasing surfaces with nanotubular structures.

A new approach to engineer a local drug delivery system with delayed release using nanostructured surface with nanotube arrays is presented. TNT arrays electrochemically generated on a titanium surface are used as a model substrate. Polymer micelles as drug carriers encapsulated with drug are loaded at the bottom of the TNT structure and their delayed release is obtained by loading blank micelles (without drug) on the top.

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

Unlabelled: 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.

Surface-functionalized diatom microcapsules for drug delivery of water-insoluble drugs.

Naturally available and biocompatible materials are potential substitutes for synthetic mesoporous materials as suitable drug carriers for the development of cost-effective drug delivery systems. This work investigates the application of a porous silica material derived from diatoms, also known as diatomaceous earth. The aim is to explore the surface functionalization of diatom microcapsules and their impact on the drug loading and release characteristics of water-insoluble drugs.

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.

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.

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.

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.

Surface functionalisation of diatoms with dopamine modified iron-oxide nanoparticles: toward magnetically guided drug microcarriers with biologically derived morphologies.

Diatom silica microcapsules prepared by purification of diatomaceous earth (DE) were functionalised by dopamine modified iron-oxide nanoparticles, in order to introduce diatoms with magnetic properties. The application of magnetised diatoms as magnetically guided drug delivery microcarriers has been demonstrated.