Boron nitride nanotubes : a novel vector for targeted magnetic drug delivery

Whereas several biomedical applications of carbon nanotubes have been proposed, the use of boron nitride nanotubes (BNNTs) in this field has been largely unexplored despite their unique and potentially useful properties. Our group has recently initiated an experimental program aimed at the exploration of the interactions between BNNTs and living cells. In the present paper, we report on the magnetic properties of BNNTs containing Fe catalysts which confirm the feasibility for their use as nanovectors for targeted drug delivery. The magnetisation curves of BNNTs characterised by the present study are typical of superparamagnetic materials with important parameters, including magnetic permeability and magnetic momentum, derived by employing Langevin theory. In-vitro tests have demonstrated the feasibility for influencing the uptake of BNNTs by living cells by exposure to an external magnetic source. A finite element method analysis devised to predict this effect produced predictive data with close agreement with the experimental observations.

Design and construction of a micropump for drug delivery applications

This paper presents design, construction, and evaluation of a micropump for drug delivery applications. The proposed micropump consists of three components: fluidics, electronics, and software. The fluidics component includes a silicone elastic diaphragm, a microservo, housing and two check valves. The diaphragm is modeled and simulated to establish its geometrical specifications. The housing is built using a rapid prototype machine. The electronics component consists of a microcontroller, a microswitch array, a simple display and a power unit. The software component is written in C and receives inputs from user, controls the microservo speed and displays the programmed speed. A number of experiments are conducted to evaluate the performance and capabilities of the micropump. The experiments focus on measurement of flow rate, dosage and duration of operation. A discussion of the performance and capabilities of the developed micropump is also given.

Chimeric aptamers in cancer cell-targeted drug delivery

Aptamers are single-stranded structured oligonucleotides (DNA or RNA) that can bind to a wide range of targets ("apatopes") with high affinity and specificity. These nucleic acid ligands, generated from pools of random-sequence by an in vitro selection process referred to as systematic evolution of ligands by exponential enrichment (SELEX), have now been identified as excellent tools for chemical biology, therapeutic delivery, diagnosis, research, and monitoring therapy in real-time imaging. Today, aptamers represent an interesting class of modern pharmaceuticals which with their low immunogenic potential mimic extend many of the properties of monoclonal antibodies in diagnostics, research, and therapeutics. More recently, chimeric aptamer approach employing many different possible types of chimerization strategies has generated more stable and efficient chimeric aptamers with aptameraptamer, aptamernonaptamer biomacromolecules (siRNAs, proteins) and aptamernanoparticle chimeras. These chimeric aptamers when conjugated with various biomacromolecules like locked nucleic acid (LNA) to potentiate their stability, biodistribution, and targeting efficiency, have facilitated the accurate targeting in preclinical trials. We developed LNA-aptamer (anti-nucleolin and EpCAM) complexes which were loaded in iron-saturated bovine lactofeerin (Fe-blf)-coated dopamine modified surface of superparamagnetic iron oxide (Fe3O4) nanoparticles (SPIONs). This complex was used to deliver the specific aptamers in tumor cells in a co-culture model of normal and cancer cells. This review focuses on the chimeric aptamers, currently in development that are likely to find future practical applications in concert with other therapeutic molecules and modalities.

Nanotechnology based platforms for survivin targeted drug discovery

Introduction: Development of an effective, safe and targeted drug delivery system to fight cancer and other diseases is a prime focus in the area of drug discovery. The emerging field of nanotechnology has revolutionised the way cancer therapy and diagnosis is achieved primarily due to the recent advances in material engineering and drug availability. Further, the recognition of the crucial role played by anti-apoptotic proteins such as survivin, has initiated the development of therapeutics that can target this protein as an attempt to develop alternative cancer therapies. However, a key challenge faced in drug development is the efficient delivery of survivin-targeted molecules to specific areas in the body.Areas covered: This review primarily focuses on the different strategies employing nanotechnology for targeting survivin expressed in human cancers. Different nanomaterials incorporating nucleic molecules or drugs targeted at survivin are discussed and the results obtained from studies are highlighted.Expert opinion: There are extensive studies reporting different treatment regimens for cancer, however, they still result in systemic toxicity, reduced bioavailability and ineffective delivery. Novel approaches involve the use of biocompatible nanomaterials together with gene or drug molecules to target proteins such as survivin, which is overexpressed in cancerous cells. These nanoformulations allow the benefits of protecting easily degradable molecules, allow controlled release, and enhance targeted delivery and effectiveness. Hence, nanotherapy utilizing survivin targeting can be considered to play a key role in the development of personalized nanomedicine for cancer.

Integrated microfluidic drug delivery devices : a component view

Research on drug delivery devices is progressing rapidly with the main objective being the delivery of precise quantity of drugs into the target area of the body. A drug delivery device (DDD) needs to accurately control the flow rate of drug delivery and protects the body from undesired additional doses. An integrated microfluidic drug delivery device (IMDDD) is a miniature device that can regulate and monitor the delivery of the right amount of drug using micro-scale components. IMDDDs offer several advantages including ease of use, electro-chemical controllability, low power consumption, simplicity, fast fabrication, and good bio-compatibility. Various IMDDDs have been developed for treatment of cancer, cardiovascular disorder, eye and brain diseases, stress, and diabetes. This paper presents a generic architecture for IMDDDs, discusses the existing drug delivery methods, summarizes the specifications of the components, and identifies a number of performance evaluation parameters. The operation of IMDDDs is presented through fourteen potential internal components. In addition, recommendations on how enhance the design and fabrication process of IMDDDs are given.

Synthesis and biological evaluation of novel folic acid receptor-targeted, β-cyclodextrin-based drug complexes for cancer treatment

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5-2.5 nm. The host-guest association constant Ka was 1,639 M-1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated β-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer.

Multifunctional and multitargeted nanoparticles for drug delivery to overcome barriers of drug resistance in human cancers

The recurrence and metastatic spread of cancer are major drawbacks in cancer treatment. Although chemotherapy is one of the most effective methods for the treatment of metastatic cancers, it is nonspecific and causes significant toxic damage. The development of drug resistance to chemotherapeutic agents through various mechanisms also limits their therapeutic potential. However, as we discuss here, the use of nanodelivery systems that are a combination of diagnostics and therapeutics (theranostics) is as relatively novel concept in the treatment of cancer. Such systems are likely to improve the therapeutic benefits of encapsulated drugs and can transit to the desired site, maintaining their pharmaceutical properties. The specific targeting of malignant cells using multifunctional nanoparticles exploits theranostics as an improved agent for delivering anticancer drugs and as a new solution for overriding drug resistance.