Current Topics in Medicinal Chemistry - Volume 15, Issue 4, 2015

The use of the nanotechnology in the development of new drugs has had in the last years a very widespread presence in the pharmaceutical industry. Diverse diseases that are treated by means of conventional administration systems as capsules, covered tablets or injectable not always have the therapeutic effect expected due to its bioavailability, solubility in aqueous medium and the stability of the excipients that they accompany to the drug. It is for this reason that the formation of nanoparticles either from organic sources as natural polymers like chitosan or synthetic like poly-ε-caprolactone (PCL) affording the inclusion of diverse liposoluble active compounds, they have given excellent results in the incipient treatment of behavior disorders that are necessary drugs that should remain close of active sites at the time. Thus, this review shows the formation of nanoparticles for a direct application of the psychiatric medication, may be considered as a new pharmacological tool by its low cytotoxicity and high efficiency.

Coordination compounds are substances in which a central metal atom is bonded to nonmetal atoms, or groups of atoms, called ligands. Examples include vitamin B12, hemoglobin, chlorophyll, dyes and pigments, as well as catalysts used in organic synthesis. Coordination compounds have received much attention in recent years. This interest was prompted by the discovery that several coordination compounds exhibit activity against bacteria, fungi and cancer. Some coordination compounds are not in clinical use, because of poor water solubility. Because they are unable to cross the lipid membranes of cells, bioavailability and efficacy are low. Some researchers have applied nanotechnology to coordination compounds, hoping to reduce the number of doses required and the severity of side effects, and also to improve biological activity. Nanotechnology can deliver active components in sufficient concentrations throughout treatment, guiding it to the desired location of action; conventional treatments do not meet these requirements. In this study we review some drug delivery systems based on nanotechnology, such as microemulsions (MEs), cyclodextrin (CD), polymeric nanoparticles (PN), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), magnetic and gold nanoparticles (MNPs / AuNPs) and liquid crystalline systems (LC), and coordination compounds.

Nitric oxide (NO) is known to have dichotomous effects on cancer biology, acting as a pro- or antineoplastic agent. Low concentrations of NO are reported to promote tumor growth, whereas high NO influx acts as a potent tumor repressor, leading to cytotoxicity and apoptosis. There is increasing interest in developing NO-releasing materials as potent tumoricidal agents in which high and localized concentrations of NO may be directly released in a sustained manner to the tumor site. Nanomaterials allied to NO donors have emerged as a promising strategy in cancer treatment. In this context, this review summarizes the roles of NO in cancer biology and highlights the therapeutic potential effects of NO-releasing nanomaterials based on polymeric nanoparticles, dendritic polymers, liposomes, silica nanoparticles, metallic nanoparticles and quantum dots in combating tumor cells.

During the last ten years, graphene oxide has been explored in many applications due to its remarkable electroconductivity, thermal properties and mobility of charge carriers, among other properties. As discussed in this review, the literature suggests that a total characterization of graphene oxide must be conducted because oxidation debris (synthesis impurities) present in the graphene oxides could act as a graphene oxide surfactant, stabilizing aqueous dispersions. It is also important to note that the structure models of graphene oxide need to be revisited because of significant implications for its chemical composition and its direct covalent functionalization. Another aspect that is discussed is the need to consider graphene oxide surface chemistry. The hemolysis assay is recommended as a reliable test for the preliminary assessment of graphene oxide toxicity, biocompatibility and cell membrane interaction. More recently, graphene oxide has been extensively explored for drug delivery applications. An important increase in research efforts in this emerging field is clearly represented by the hundreds of related publications per year, including some reviews. Many studies have been performed to explore the graphene oxide properties that enable it to deliver more than one activity simultaneously and to combine multidrug systems with photothermal therapy, indicating that graphene oxide is an attractive tool to overcome hurdles in cancer therapies. Some strategic aspects of the application of these materials in cancer treatment are also discussed. In vitro studies have indicated that graphene oxide can also promote stem cell adhesion, growth and differentiation, and this review discusses the recent and pertinent findings regarding graphene oxide as a valuable nanomaterial for stem cell research in medicine. The protein corona is a key concept in nanomedicine and nanotoxicology because it provides a biomolecular identity for nanomaterials in a biological environment. Understanding protein corona-nanomaterial interactions and their influence on cellular responses is a challenging task at the nanobiointerface. New aspects and developments in this area are discussed.

The current review aims to outline the likely medical applications of nanotechnology and the potential of the emerging field of nanomedicine. Nanomedicine can be defined as the investigation area encompassing the design of diagnostics and therapeutics at the nanoscale, including nanobots, nanobiosensors, nanoparticles and other nanodevices, for the remediation, prevention and diagnosis of a variety of illnesses. The ultimate goal of nanomedicine is to improve patient quality-of-life. Because nanomedicine includes the rational design of an enormous number of nanotechnology-based products focused on miscellaneous diseases, a variety of nanomaterials can be employed. Therefore, this review will focus on recent advances in the manufacture of soft matterbased nanomedicines specifically designed to improve diagnostics and cancer chemotherapy efficacy. It will be particularly highlighted liposomes, polymer-drug conjugates, drug-loaded block copolymer micelles and biodegradable polymeric nanoparticles, emphasizing the current investigations and potential novel approaches towards overcoming the remaining challenges in the field as well as formulations that are in clinical trials and marketed products.

New biocompatible nanomaterials are leading to a range of emerging health treatments. Thus, peptide drugs present in oral diseases, such as caries, periodontal diseases and oral cancer, are highlighting into clinical practice because the peptides can have an influence the growth of tumor cells or microorganisms and its can exhibit direct cytotoxic activity towards cancer cells or microbial cells. Therefore, it is interesting to speculate what are the natural or synthetic peptides that can be used to develop novel strategies to fight cancer diseases or microbial cells, and so, to represent a novel family of anticancer or antimicrobial agents. The use of buccal drug delivery systems, especially nanoparticles, to carrier peptides shows to be very interesting, because these systems can protect the peptide against enzymatic degradation, in addition to target inaccessible sites. However, this peptide delivery system seems to be unexplored by researchers. On the hand, the application of drug delivery systems for oral diseases could be a proposed treatment for these diseases, including the treatment or co-treatment with other therapies, such as photodynamic therapy, of antimicrobial, periodontal diseases and cancer, or even in the early diagnosis of cancer. The objective of this study is to present a systematic review of nanotechnology-based peptides delivery systems intended to oral diseases.

Nasal delivery has become a growing area of interest for drug administration as a consequence of several practical advantages, such as ease of administration and non-invasiveness. Moreover, the avoidance of hepatic first-pass metabolism and rapid and efficient absorption across the permeable nasal mucosa offer a promising alternative to other traditional administration routes, such as oral or parenteral delivery. In fact, nasal delivery has been proposed for a number of applications, including local, systemic, direct nose-to-brain and mucosal vaccine delivery. Nanoemulsions, due to their stability, small droplet size and optimal solubilization properties, represent a versatile formulation approach suitable for several administration routes. Nanoemulsions demonstrated great potential in nasal drug delivery, increasing the absorption and the bioavailability of many drugs for systemic and nose-tobrain delivery. Furthermore, they act as an active component, i.e. an adjuvant, in nasal mucosal vaccinations, displaying the ability to induce robust mucosal immunity, high serum antibodies titres and a cellular immune response avoiding inflammatory response. Interestingly, nanoemulsions have not been proposed for the treatment of local ailments of the nose. Despite the promising results in vitro and in vitro, the application of nanoemulsions for nasal delivery in humans appears mainly hindered by the lack of detailed toxicology studies to determine the effect of these formulations on the nasal mucosa and cilia and the lack of extensive clinical trials.

Blindness and visual impairment affect millions of people worldwide and have a very important impact on patients quality of life. Proteins and peptides represent nowadays an important therapeutic tool for the treatment of ocular diseases but, despite their potential, have significant limitations, as the administration of protein-based pharmaceuticals represents a real challenge. Moreover, administration of ocular medications is difficult due to the peculiar structure of this organ and the presence of numerous barriers protecting the eye inner structure. Nanoencapsulation of peptides and proteins presents a number of advantages for their ocular delivery since it can protect the drug from metabolic activity, control and sustain the release and increase drug bioavailability after topical or intravitreal administration. In fact, nanoparticulate formulations are contributing to overcome ocular barriers, such as the corneal or the blood-retinal barrier, improve the residence time in the eye, increase local drug level, reduce the drug dosage and showing improved performance when compared to conventional formulations. Besides, proteins have also been proposed for the preparation of nanocarriers intended for ophthalmic administration, since they are highly biocompatible, biodegradable and easily modified to link surface ligands. The present review focuses the attention on the use of proteins in ocular drug delivery nanotechnology: their dual role as both therapeutics and carriers has been critically evaluated and discussed.

Pulmonary drug delivery represents the best way of treating lung diseases, since it allows direct delivery of the drug to the site of action, with few systemic effects. Meanwhile, the lungs may be used as a portal of entry to the body, allowing systemic delivery of drugs via the airway surfaces into the bloodstream. In both cases, the therapeutic effect of the inhaled drug can be optimized by embedding it in appropriately engineered inhalable carriers, which can protect the drug against lung defense mechanisms and promote drug transport across the extracellular and cellular barriers. To this purpose, the attention has been very recently focused on polymeric nanoparticles (NPs). The aim of this review is to offer an overview on the recent advances in NPs for pulmonary drug delivery. After a description of the main challenges encountered in developing novel inhaled products, the design rules to engineer polymeric NPs for inhalation, and in so doing to overcome barriers imposed by the lungs anatomy and physiology, are described. Then, the state-of-art on inhalable biocompatible polymeric NPs based on enzymaticallydegradable natural polymers and biodegradable poly(ester)s is presented, with a special focus on NP-based dry powders for inhalation. Finally, the in vitro/in vivo models useful to address the never-ending toxicological debate related to the use of NPs for inhalation are described.

Chitosan (CS) based nanocarriers have been extensively studied starting from early 90s. The unique properties of CS and in particular its capability to interact with various epithelia and its mucoadhesion potential have attracted many researchers. The mild preparation conditions of CS nanosystems offer the opportunities to load stress sensitive hydrophilic macromolecules such as proteins and genetic materials. Moreover CS nanosystems are able to protect their cargo from the environment (pH, enzymes). The safety issues related to this polymer seem in part overcome at least for CS as polymeric solution. For this reason skin and mucosae, in particular buccal and vaginal ones, seem the more promising administration routes with lower technical and regulatory challenges. Even if several papers focused on CS nanocarriers for skin and mucosal (buccal and vaginal) administration have been published, other work should be done aiming at optimizing CS nanocarriers in view of clinical applications.