Objectives
This review highlights both the physicochemical characteristics of the nanocarriers (NCs) and the physiological features of tumour microenvironment (TME) to outline what strategies ...undertaken to deliver the molecules of interest specifically to certain lesions. This review discusses these properties describing the convenient choice between passive and active targeting mechanisms with details, illustrated with examples of targeting agents up to preclinical research or clinical advances.
Key findings
Targeted delivery approaches for anticancers have shown a steep rise over the past few decades. Though many successful preclinical trials, only few passive targeted nanocarriers are approved for clinical use and none of the active targeted nanoparticles. Herein, we review the principles and for both processes and the correlation with the tumour microenvironment. We also focus on the limitation and advantages of each systems regarding laboratory and industrial scale.
Summary
The current literature discusses how the NCs and the enhanced permeation and retention effect impact the passive targeting. Whereas the active targeting relies on the ligand‐receptor binding, which improves selective accumulation to targeted sites and thus discriminates between the diseased and healthy tissues. The latter could be achieved by targeting the endothelial cells, tumour cells, the acidic environment of cancers and nucleus.
This review article presents the state-of-the-art in the major imaging modalities supplying relevant information on patient health by real-time monitoring to establish an accurate diagnosis and ...potential treatment plan. We draw a comprehensive comparison between all imagers and ultimately end with our focus on two main types of scanners: X-ray CT and MRI scanners. Numerous types of imaging probes for both imaging techniques are described, as well as reviewing their strengths and limitations, thereby showing the current need for the development of new diagnostic contrast agents (CAs). The role of nanoparticles in the design of CAs is then extensively detailed, reviewed and discussed. We show how nanoparticulate agents should be promising alternatives to molecular ones and how they are already paving new routes in the field of nanomedicine.
Attractive interest on double emulsions comes from their unique morphology, making them general multifunctional carriers able to encapsulate different hydrophilic and lipophilic molecules in the same ...particle. Over the past century, two different types of methods were followed to prepare double emulsions for pharmaceutics applications, so-called “one-step” and “two-step” processes. The two-step approach, consisting in two different emulsifications successively performed, allows the optimal and more efficient formulations due to simplicity of principle and controllability of the process. In this review, focused on the formulation of double emulsions by two-step process, we recount the historical development of this approach, along with the state-of-the-art, including a discussion on the role of the formulation parameters, surfactants, amphiphilic polymers, interface stabilization, volume fraction, and so forth, on the final formulation stability, morphology and properties as drug delivery system. Discussion was also extended to polymeric microparticles and nanoparticles made by solvent diffusion, on the basis of double emulsions made by two-step process, along with literature review on the impact of different formulation and processing parameters. In addition, the properties of the polymers used in the microparticles matrix (molecular weight, chemical nature) potentially impacting on the ones of the microparticles formed (drug release kinetics, stability, morphology), were also discussed. Finally, the future trends in double emulsions application were addressed, emphasizing some new advances made in the emulsifications method as potentially able to open the range of applications, for example to nanoscale with spontaneous emulsification or low energy microfluidic emulsification.
Display omitted
Advances in molecular biology have significantly increased the understanding of the biology of different diseases. However, these discoveries have not yet been fully translated into improved ...treatments for patients with diseases such as cancers. One of the factors limiting the translation of knowledge from preclinical studies to the clinic has been the limitations of in vivo diseases models. In this brief review, we will discuss the advantages and disadvantages of rodent models that have been developed to simulate human pathologies, focusing in models that employ xenografts and genetic modification. Within the framework of genetically engineered mouse (GEM) models, we will review some of the current genetic strategies for modeling diseases in the mouse and the preclinical studies that have already been undertaken. We will also discuss how recent improvements in imaging technologies may increase the information derived from using these GEMs during early assessments of potential therapeutic pathways. Furthermore, it is interesting to note that one of the values of using a mouse model is the very rapid turnover rate of the animal, going through the process of birth to death in a very short timeframe relative to that of larger mammalian species.
The current nanotechnology era is marked by the emergence of various magnetic inorganic nanometer-sized colloidal particles. These have been extensively applied and hold an immense potential in ...biomedical applications including, for example, cancer therapy, drug nanocarriers (NCs), or in targeted delivery systems and diagnosis involving two guided-nanoparticles (NPs) as nanoprobes and contrast agents. Considerable efforts have been devoted to designing iron oxide NPs (IONPs) due to their superparamagnetic (SPM) behavior (SPM IONPs or SPIONs) and their large surface-to-volume area allowing more biocompatibility, stealth, and easy bonding to natural biomolecules thanks to grafted ligands, selective-site moieties, and/or organic and inorganic corona shells. Such nanomagnets with adjustable architecture have been the topic of significant progresses since modular designs enable SPIONs to carry out several functions simultaneously such as local drug delivery with real-time monitoring and imaging of the targeted area. Syntheses of SPIONs and adjustments of their physical and chemical properties have been achieved and paved novel routes for a safe use of those tailored magnetic ferrous nanomaterials. Herein we will emphasis a basic notion about NPs magnetism in order to have a better understanding of SPION assets for biomedical applications, then we mainly focus on magnetite iron oxide owing to its outstanding magnetic properties. The general methods of preparation and typical characteristics of magnetite are reviewed, as well as the major biomedical applications of magnetite.
ABSTRACT
Much research has been done over the past years on self-emulsifying drug delivery systems, their main interest being the simplicity of the formulation processes, the great stability of the ...systems and their high potential in pharmaceutical applications and industrial scaling-up. Self-emulsifying drug delivery systems are generally described in the literature indiscriminately as either nano-emulsions or micro-emulsions. Although this misconception appears to be common, these two systems are fundamentally different, based on very different physical and physicochemical concepts. Their differences result in very different stability behaviors, which can have significant consequences regarding their applications and administration as nanomedicines. This paper aims at clarifying the problem, first by reviewing all the physical and physicochemical fundamentals regarding these two systems, using a quantitative thermodynamic approach for micro-emulsions. Following these clarifications, we show how the confusion between nano-emulsions and micro-emulsions appears in the literature and how most of the micro-emulsion systems referred to are actually nano-emulsion systems. Finally, we illustrate how to clear up this misconception using simple experiments. Since this confusion is well established in the literature, such clarifications seem necessary in order to improve the understanding of research in this important field.
Extensive studies have been done on nano-emulsions and emulsification methods to provide nanometric-scaled templates for the formulation of nanoparticles. The so-called “low-energy” methods are of ...particular interest as they prevent the potential degradation of fragile encapsulated molecules. This work deals with new concepts in nano-emulsification using low-energy methods. Three-model ternary systems, water/nonionic surfactant/oil, were studied and compared. Nano-emulsions were generated using both spontaneous emulsification and the PIT method, so as to study the links between these two nano-emulsification methods. The influence of the composition and formulation variables on the nano-emulsion properties and emulsification procedures were thus investigated. This study pioneers the concept of the universality of low-energy nano-emulsification, proving that all these low-energy methods (
i.e. spontaneous emulsification and the phase inversion temperature (PIT) method) are governed by a single unique mechanism. It thus provides a better understanding of low-energy nano-emulsification processes and notably the PIT method, useful in the fields of nanoparticle and nano-pharmaceutic formulations. These results are fundamental in establishing experimental procedures for the incorporation of drugs in nano-emulsions.
Spray drying technology is widely known and used to transform liquids (solutions, emulsions, suspension, slurries, pastes or even melts) into solid powders. Its main applications are found in the ...food, chemical and materials industries to enhance ingredient conservation, particle properties, powder handling and storage etc. However, spray drying can also be used for specific applications in the formulation of pharmaceuticals for drug delivery (
e.g. particles for pulmonary delivery). Büchi is a reference in the development of spray drying technology, notably for laboratory scale devices. This study presents the Nano Spray Dryer B-90, a revolutionary new sprayer developed by Büchi, use of which can lower the size of the produced dried particles by an order of magnitude attaining submicron sizes. In this paper, results are presented with a panel of five representative polymeric wall materials (arabic gum, whey protein, polyvinyl alcohol, modified starch, and maltodextrin) and the potentials to encapsulate nano-emulsions, or to formulate nano-crystals (
e.g. from furosemide) are also shown.
One of the factors limiting the translation of knowledge from preclinical studies to the clinic has been the limitations of in vivo diseases models. Except in the case of highly controlled and ...regulated clinical trials, geneticists and scientists do not use humans for their experimental investigations because of the obvious risk to life. Instead, they use various animal, fungal, bacterial, and plant species as model organisms for their studies. Amongst these model organisms, rodent models are the most used due to the easiness for the experiments and the possibility to modify genetically these model animals. Nevertheless, due to the fact that animal models typically do not contract the same genetic diseases as people, so scientists must alter their genomes to induce human disease states and to know what kind of mutation causes the disease. In this brief review, we will discuss the interests of rodent models that have been developed to simulate human pathologies, focusing in models that employ xenografts and genetic modification. Within the framework of genetically engineered mouse (GEM) models, we will review some of the current genetic strategies for modeling diseases.
Hyaluronic acid (HA) is widely used for numerous medical applications, such as viscosupplementation, eye surgery and drug delivery. A broad range of HA-based materials have been developed and ...described for the enhancement, modulation and control of its therapeutic action, based on chemical modification of polysaccharides. The purpose of this paper is to review the various chemical modification methods and synthetic routes to obtain HA derivatives, encompassing all applications.
PDF
