Current Pharmaceutical Design - Volume 21, Issue 36, 2015

Nanomedicine is an emerging and rapidly growing field, possibly exploring for high expectation to healthcare. Nanoformulations have been designed to overcome challenges due to the development and fabrication of nanostructures. Unique size-dependent properties of nanoformulations make them superior and indispensable in many areas of human activity. Nano drug delivery systems are formulated and engineered to carry and deliver a number of substances in a targeted and controlled way. The vision of nanocarriers can be designed that will serve a dual purpose, allowing both treatment and diagnosis to be contained in an ‘all-in-one’ package. Nanoscale drugdelivery systems efficiently regulate the release, pharmacokinetics, pharmacodynamics, solubility, immunocompatibility, cellular uptake and biodistribution of chemical entities (drug). Their cellular uptake takes place by various mechanisms such as micropinocytosis, phagocytosis and receptor mediated endocytosis. These phenomena cause longer retention in blood circulation resulting in the release of the encapsulated materials in a sustained manner thus minimize the plasma fluctuations and toxic side effects. In this manner, the therapeutic index of conventional pharmaceuticals is efficiently increased. They can be used to deliver both micro and macro biomolecules such as peptides, proteins, plasmid DNA and synthetic oligodeoxynucleotides. In this present review, several recent developing and modifying nano-products for the detection, analysis, and treatment of diseases with their US and world patents along with various diagnostic kits have been discussed.

Osteosarcoma (OS) is one of the most serious malignancies along with a high incidence in children and teenagers. Although the neoadjuvant chemotherapy of OS has made great progress and prolongs the five-year survival rates of patients to some extent, drugs are restrained from clinical application due to the unsatisfactory efficacy and severe side effects, especially for the systemic therapy through intravenous injection. The polymeric nanoparticles as anti-cancer drug nanocarriers make OS treatment more promising and effective. Specifically, various polymeric nanoparticles have been developed to overcome the difficulties in targeting delivery of drugs to OS tissue and/or cells through passive and/or active strategies. This review presents an overview on the development of polymeric nanoparticles for anti-cancer drug delivery in OS treatment, and briefly describes the challenge and opportunity for future development.

Mucosal drug delivery is considered as a convenient, mild and safe route, especially for the treatment of chronic diseases. In general, mucosal routes include buccal, ocular, intranasal, pulmonary, vaginal and oral delivery. To increase the efficiency of mucosal delivery, nanocarriers have been extensively explored, of which lipidbased nanocarriers attract much attention due to their great biocompatibility, cell membrane affinity and other excellent physicochemical properties by using different kinds of lipids. However, the effectiveness of lipid-based nanocarriers is limited by numerous in vivo physiological barriers (e.g. chemical environment, mucus and epithelium) in tracts or cavities. Herein, modification strategies of these nanocarriers are widely investigated and show great improvement of drug bioavailability. The aim of this review is to introduce applications of lipid-based nanocarriers in different mucosal routes and discuss typical modification strategies.

The majority of pharmaceutical formulations for the treatment of ocular pathologies are for topical administration. However, this kind of ophthalmic formulations has disadvantages such as low bioavailability and, consequently, a reduced therapeutic effect. This happens due to the anatomical and physiological specificity of the eyeball (tissues with different characteristics, the presence of different defense mechanisms, etc.) effects, reducing the residence time of formulation in contact with the ocular surface and consequently fall dramatically the penetration ability of the formulation through the ocular tissues. The repeated administration of this type of ophthalmic formulations with the aim to produce the desired therapeutic effect leads to the appearance of side effects due to its systemic absorption. In order to overcome the weaknesses of this type of therapy is necessary to use different strategies. In this review article, we discuss some of these different strategies, with particular emphasis on the application of colloidal dispersions in ophthalmic formulations, particularly, the use of polymeric and lipid nanoparticles. In fact, the results of the published scientific research has demonstrated that the use of this type of strategy not only promotes the increase in the precorneal residence time of the ophthalmic formulation, but also the ability to penetrate through the ocular tissues, enhancing the drug bioavailability and the therapeutic efficacy of ophthalmic formulations. Finally, it is also given emphasis not only to the current state of the scientific research in this area, but also to the existing patents and the followed procedure to place on the market an ophthalmic formulation based on nanoparticles.

The aim of the present paper is to highlight the potential of nasal mucosa as an administration route for targeting the central nervous system, in particular, the brain. Among the formulation strategies for enhance nose to brain drug delivery, the use of colloidal carriers has became a revolutionary approach. These systems should be able to entrap drugs in the desired amount, to penetrate through anatomical barriers, to efficiently release the loaded drugs in the site of action and moreover to show a good physicochemical, biological stability and good biocompatibility. The use of vesicular systems (liposomes and niosomes) together with the use of micelles, in nose to brain delivery are here presented. Vesicle structure is characterized by the presence of a hydrophobic bilayer and an aqueous core that is absent in micelles. Amphiphilic molecules are responsible for soft nanocarriers formation, in particular: liposomes are formed by phospholipids, while niosomes by non-ionic surfactant and micelles by amphiphilic polymers.

Inhalation of aerosolized compounds is a popular, non-invasive route for the targeted delivery of therapeutic molecules to the lung. Various types of nanoparticles have been used as carriers to facilitate drug uptake and intracellular action in order to treat lung diseases and/or to facilitate lung repair and growth. These include polymeric nanoparticles, liposomes, and dendrimers, among many others. In addition, nanoparticles are sometimes used in combination with small molecules, cytokines, growth factors, and/or pluripotent stem cells. Here we review the rationale and state-of-the-art nanotechnology for pulmonary drug delivery, with particular attention to new technological developments and approaches as well as the challenges associated with them, the emerging advances, and opportunities for future development in this field.

Vaccination is the most cost-effective and the best prophylactic strategy for the treatment of many diseases and, therefore, is widely used to improve human health. However, currently, most vaccines are given by injection which has a number of intrinsic disadvantages, such as inoculation needing professionals, waste metal needle pollution and infection, and low vaccination compliance. To overcome these drawbacks, in the past two decades a variety of microneedles have been developed and these are increasingly being widely tried to deliver vaccines due to many prominent advantages, such as their convenience, and effectiveness, over other delivery systems. In particular, the biocompatible material-constituted microneedle arrays (bioMMAs) that are fabricated with biocompatible materials in the form of a matrix or formulated micro/nanoparticles, such as liposomes, PLA/PLGA/ chitosan nanoparticles, hydrogels, polyelectrolyte multiplelayers (PEMs), plasmids, and nonvirulent pathogens, have proven an effective and stable vaccine adjuvant-delivery system (VADS) allowing painless vaccination via the cutaneous or mucosal route by minimally trained workers or by self-administration. When given to mammals through the skin or oral mucosa where affluent professional antigen-presenting cells (APCs), such as Langerhans cells, dendritic cells and macrophages, are actively patrolling for immune surveillance, the bioMMAs can efficiently elicit robust systemic as well as mucosal immunoresponses against the loaded antigens. In addition, when different vaccine adjuvants, such as TLR (toll-like receptor) ligands, have been incorporated, the bioMMAs can govern and redirect the immunoresponse toward a Th1, Th2 or a mixed Th1/Th2 pathway to establish cellular and humoral immunity to the target pathogens. In this review, various types of bioMMAs used as a VADS are described to show the latest advances and their diverse uses and potential applications in vaccine-related fields.

Glioblastoma multiforme (GBM) is one of the most challenging diseases to treat in clinical oncology due to its high mortality rates and inefficient conventional treatment methods. Difficulties with early detection, post-surgical recurrences, and resistance to chemotherapy and/or radiotherapy are important reasons for the poor prognosis of those with GBM. Over the past few decades, magnetic resonance (MR) theranostics using magnetic nanoparticles has shown unique advantages and great promises for the diagnosis and treatment of cancers. Magnetic nanoparticles not only serve as "molecular beacons" to enhance tumor contrast in magnetic resonance imaging (MRI), but also serve as "molecular bullets" for targeted drug delivery, controlled release, and induced hyperthermia. Moreover, multiple functions of magnetic nanoparticles can be synergistically engineered into a single nanoplatform, making it possible to simultaneously image, treat, target, and monitor the targeted lesions. The multi-functionality of nanoparticles, also called nano-theranostics, gives rises to effective new approaches for combating GBM. In this work, recent research and progress concerning the applications of MR nano-theranostics on GBM using magnetic nanoparticles will be highlighted, focusing on topics such as diagnosis, therapy, targeting, and hyperthermia, as well as outstanding challenges for MR nanotheranostics in treating GBM. The conclusions are generally applicable to other types of brain tumors.

Atherosclerosis is a systemic disease characterized by the development of multifocal plaque lesions within vessel walls and extending into the vascular lumen. The disease takes decades to develop symptomatic lesions, affording opportunities for accurate detection of plaque progression, analysis of risk factors responsible for clinical events, and planning personalized treatment. Of the available molecular imaging modalities, radionuclidebased imaging strategies have been favored due to their sensitivity, quantitative detection and pathways for translational research. This review summarizes recent advances of radiolabeled small molecules, peptides, antibodies and nanoparticles for atherosclerotic plaque imaging during disease progression.

Resveratrol (3,5,4’-trihydroxy-trans-stilbene), a natural phytoalexin found in grape-skin, exerts multiple biological activities, including anti-inflammatory, antiproliferative and antioxidant effects. In the past few years, mounting evidence has suggested that resveratrol is neuroprotective against a number of neurological diseases. An important contributor to the pathogenesis of neurological disorders is neuroinflammation, of which microglial activation is an important hallmark. It is possible that M1/M2 polarization of microglia may play an important role in controlling the balance between promoting and resolving neuroinflammation in the CNS. Immunomodulatory strategies capable of redirecting the microglial response toward the neuroprotective M2 phenotype could offer attractive options for neurodegenerative diseases with inflammatory components. The neuroprotective actions of resveratrol seem to be attributable to its anti-inflammatory properties, due not only to its direct scavenger effects versus toxic molecules but also to a capacity to upregulate natural anti-inflammatory defences, thus counteracting excessive responses of classically activated M1 microglia. The goal of this review is to summarize recent insights into the therapeutic potential of resveratrol as a natural modulator of microgliamediated neurotoxicity.

Type 1 diabetes (T1DM) is a disease characterized by autoimmune mediated destruction of the insulin producing beta cells of endocrine pancreas. Beside insulin deficiency, T1DM is also characterized by abnormal suppression of glucagon secretion in response to hyperglycemia. All these abnormalities are likely to leave patients dependent upon exogenous insulin administration for survival. GLP-1 is a hormone secreted by L-cells of distal small intestine and colon. GLP-1 exerts its effects through the interaction with GLP-1 receptor expressed in the pancreatic islets, lung, hypothalamus, stomach, heart and kidney. It belongs to the group of incretin peptides and it stimulates insulin and inhibits glucagon secretion. Actions of GLP-1 also include delaying of gastric emptying, reduction of appetite and induction of satiety. On the other hand, evidences mainly collected from animal models, have indicated the role of GLP-1 in increasing beta cell proliferation and differentiation and in decreasing the rate of beta cell apoptosis. GLP-1 receptor agonists are approved for the treatment of type 2 diabetes where they have established very important position. However, they are still not approved for use in T1DM, although they could have beneficial effects in both new onset and longstanding T1DM patients, mainly as an adjunctive therapy to insulin in order to improve glycemic control and body weight management in longstanding disease or to reduce insulin requirements or even to delay the absolute dependence upon insulin administration in new onset T1DM. Randomized, long-term, placebo controlled clinical trials are warranted before the official implementation of GLP-1 receptor agonists in the treatment of T1DM.