Journal of interdisciplinary nanomedicine最新文献

Shahd Abuhelal ([email protected])*

King's College London/Institute of Pharmaceutical Science

siRNA treatment can result in decreased protein expression and could be used to treat cancer or other diseases. Successful application depends on efficient delivery inside target cells. Here, we aim to design and optimise a nano-carrier suitable for siRNA delivery, with high encapsulation efficiency and stability for use in vitro and in vivo to target cancer.

Liposomes and pH-sensitive peptides assembled as ternary complex were investigated as siRNA delivery systems. Physicochemical characteristics (size, zeta potential, siRNA maintenance, release and aggregation) were tested. Cell uptake and luciferase knock down were evaluated in vitro, and some complexes tested for biodistribution in vivo.

Hydrodynamic size and zeta potential of the lipoplex, peptide complexes and ternary complexs were similar. Although lipoplexes showed better encapsulation, they were less stable in serum. Ternary complexes offered better protection for the siRNA. Improved cell uptake was seen for ternary complexes in comparison with peptide complex and lipoplex. Knock down studies revealed optimal effects ternary complexes, and preliminary in vivo experiments showed tumour accumulation of lipoplex.

These siRNA delivery vehicles appear promising for in vivo applications, and work is now focused on the improvement of cell targeting, in vitro and in vivo PK/PD.

Chris Adams ([email protected])*

Keele University

Magnetic nanoparticles (MNPs) are key translational platforms with the ability to label cells for non-invasive imaging and genetically engineer cells for release of therapeutic biomolecules. We show for the first time that application of magnetic fields can safely enhance MNP mediated labelling and genetic engineering of autologous canine olfactory mucosal cells (cOMCs), a key veterinary cell population for treatment of spinal injury in companion dogs. Crucially, the developed protocols were successfully combined with advanced minicircle DNA vectors to deliver brain derived neurotrophic factor (important in promoting nerve fibre outgrowth) to cOMCs. Minicircles have distinct advantages for clinical gene delivery due to their small size, lack of bacterial backbone and duration of transgene expression. Finally, we also show that MNP labelling can facilitate imaging of cOMCs encapsulated in implantable collagen hydrogels using non-invasive magnetic resonance imaging. A combination of these methodologies could enable translation of safe and effective cOMC transplantation strategies.

Mohammad Ahmad Abdallah Al-Natour ([email protected])*

University and Institution: University of Nottingham

Abstract

Recent years have witnessed unexpected growth of research on the medical applications of nanotechnology (nanomedicine), especially the

Nanomedicine aims to apply and further develop nanotechnology to solve problems in medicine, related to diagnosis, treatment and/or disease prevention at the cellular and molecular level (Feng, 2006; Feng and Chien, 2003). Nanomedicine by nature is interdisciplinary, with benefits being realized at the interface of science and engineering, physical science and engineering, chemical science and engineering, cellular and molecular biology, pharmacology and pharmaceutics, medical sciences and technology and combinations thereof. The difference in perspective between disciplines may be partly responsible for the lack of nomenclature or universally-accepted definition for various “nano” terms, which causes issues with respect to publication consistency, regulatory agencies, patent offices, industry and the business community (Rannard & Owen, 2009; Tinkle et al., 2014; Bawa, 2013; Bawa, 2016). Regulatory agencies such as the US Food and Drug Administration (FDA; http://www.fda.gov/) and European Medicines Agency (EMA; http://www.ema.europa.eu/ema/) have generally failed to employ an interdisciplinary approach to regulate nanoscale technologies in the same manner as they apply to drugs because they do not fully appreciate the interdisciplinary nature or novel characteristics of many submissions that disclose nanomedicines (e.g., as a result of high-surface-area to-volume ratio, inherent reactivity due to a greater proportion of exposed surface atoms, unpredictable properties, or toxicity profiles as compared to bulk). Currently, these agencies instead rely upon established laws and regulations validated through experience with conventional small molecule medicines. Synthesis and characterization of molecular biomaterials forms the material basis for nanomedicines. Molecular biomaterials may include synthesized biocompatible polymers such as currently accepted biodegradable polymers including polylactic acid (PLA), polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA), or molecularly engineered macromolecules such as lipids, DNAs, RNAs, proteins and peptides. Such biomaterials are either used to stabilize nanosized particles of drug or to form nano-carrier technologies for sustained, controlled or targeted release of diagnostic and therapeutic agents to enhance their biological effects and to reduce their side effects (Feng et al., 2007; Owen, 2014; Bawa, 2016).

Similarly, patent offices also often fail to recognize that an interdisciplinary approach needs to be applied by patent examiners while reviewing nanotechnology-based patent applications, since the technologies reflected in these patent applications often involve a combination of disciplines. In fact, non-uniform or improper patent prosecution is the major reason for the issuance of patents of dubious scope and breadth where the patent holder is u