Current Drug Metabolism - Volume 16, Issue 8, 2015

Multiple sclerosis (MS) is characterized by inflammation, demyelination and lesions in the central nervous system (CNS) that results in the physical and cognitive disabilities in patients. Immune cells get access into the brain region, after infection in the blood brain barrier (BBB) due to bacteria/virus or by genetic predisposition, where the autoimmune response may induce the demyelination, inflammation as well as neurodegeneration in brain areas. Various types of therapeutics are used worldwide approved by the food and drug administration (FDA) for the management of MS. Hence, side effects of conventional therapy goes hand in hand. The advancement in nanomedicines have opened window for the management of various disorders of neurodegeneration including MS. Various clinical trials are in process to explore the etiology of MS and in this connection animal models like experimental autoimmune encephalomyelitis (EAE) have promising outcomes for the management of MS by using nanomedicines that give new insights. The current review elaborates the scope of nanomedicines with respect to MS patients.

As we enter the twenty-first century, several therapies based on using nanoparticles (NPs) ranging in size 1 – 1000 nm have been successfully brought to the clinic to treat cancer, pain and infectious diseases. These therapies bring together the ability of NPs to target the delivery of drugs more precisely, to improve solubility, to prevent degradation, to improve their therapeutic index and to reduce the immune response. NPs come in all shapes and sizes, designed specifically for biomedical applications such as solid lipid polymers, liposomes, dendrimers, nanogels, and quantum dots. These NPs offer many attractive characteristics such as biological stability and biocompatibility, thus incorporating different biological or drug molecules. Among the major therapeutic challenges from neurological diseases through to cancer is the development of nanomaterials that are able to be effective against the disease. In the case of neurodegeneration, one of the most difficult areas to penetrate for drug discovery in the body is the central nervous system, protected by the blood-brain-barrier. Whilst in the case of cancer, the biggest problem is how to specifically target a tumor with sufficient drug without causing side effects or inducing resistance. A new generation of intelligent NPs are emerging for the treatment of human disease such as neurological disorders and cancer. The use of natural alternative therapy is an encouraging idea in drug discovery. To this end as we gain more knowledge into the biological function of exosomes, this will allow us to harness their potential as natural NPs in future therapeutics.

Chemotherapeutic delivery by oral route in cancer patients has the potential to create “hospitalization free chemotherapy” which is a vision of oncologists, formulation scientists and patients. Such a therapeutic approach will improve patients’ compliance, ease the burden of the patients’ caregivers and significantly reduce the cost of treatment. In current clinical practice, chemotherapy carried out by intravenous injection or infusion leads to undesired side-effects such as plasma concentrations crossing the maximum safe concentration, rapid body clearance and lower bioavailability. Despite the presence of challenges such as poor aqueous solubility and stability of drugs and the presence of biological barriers like multidrug efflux transporter in the GI tract, oral cancer chemotherapy has the potential to surmount those obstacles. Lipid nanoparticles (LNPs) such as solid lipid nanoparticle, nanostructured lipid carriers, nano lipid–drug conjugates, mixed micelles, liposomes and nanoemulsions have shown some promising results for use in oral anticancer drug delivery through nanotechnological approach. LNPs demonstrate enhanced oral bioavailability owing to their ability to inhibit first pass metabolism via lymphatic absorption by chylomicron-linked and/or M-cell uptake. LNPs reduce the inter- and intrasubject pharmacokinetics variability of administrated drugs. Moreover, certain classes of phospholipids and surfactants used in the formulations of LNPs can suppress the P-glycoprotein efflux system. Here, we shall be discussing the biopharmaceutical challenges in oral cancer chemotherapy and how the LNPs may provide solutions to such challenges. The effect of GI tract environment on LNPs and pharmacokinetics shall also be discussed.

Currently the major research highlights of bioengineering and medical technology are directed towards development of improved diagnostic techniques to screen complex diseases. Screening requirements are to identify the cause of illnesses, monitor improvement or progression of the state of diseases such as cancer, cardiovascular or neurodegenerative diseases. Nanotechnology enables the manipulation of materials at nanoscale and has shown potential to enhance sensitivity, selectivity and lower the cost of a diagnosis. The causative biomolecules (DNA, proteins) can be detected by red-shifted absorbance of gold nanoparticles or alteration in the conductance of a nanowire or nanotubes, and deflection of a micro or nano-cantilever. Several types of nanomaterials such as metals, metal-oxides and quantum dots have shown ample advantages over traditional diagnosis, intracellular labeling and visualization of target cells/tissues. Nanotechnology has also opened several avenues which could be further developed to enable enhanced visualization of tissues, cells, DNA and proteins over a point-of-care device. Protein or gene chips created using nanomaterials could further be integrated into a convenient nano-fluidic device for better disease diagnosis.

Cancer is considered as a prevalent cause of human deaths and undoubtedly, is the most complex disease with multiple cellular physiological systems involved. During the last decade, the application of nanotechnological products for cancer treatment has received considerable attention. These sophisticated tools and materials treat cancer though the early diagnosis, the prediction, the prevention and the personalized therapy. This technology enabled the development of nanoscale particles that can be conjugated with one or multiple functional molecules simultaneously. Nanoparticles have the capability to be delivered directly through blood vessels to the tumor site and interact with targeted tumor-specific proteins located inside or on the surface of cancer cells, since their size is a hundred to thousand times smaller than cancer cells. In this review, comprehensive outline of all the latest scientific and technological applications such as quantum dots and gold nanoparticles alongside with their applications in cancer diagnosis and treatment have been presented.

Our modern era is witnessing an increased prevalence of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and brain tumors. This is accompanied by an increased production of nanoparticles (NPs) and the subsequent release of NPs in the environment shared by humans. NPs are extremely small molecules measuring about 100 nm in diameter. Due to minuscule size, NPs have the potential to penetrate human body through various pathways and eventually cross the blood-brain barrier to potentially cause neurotoxicity, neuroinflammation and neurodegeneration of the central nervous system. Until recently, the mechanisms by which NPs cause neuroinflammation and neurodegeneration were unknown. However, recent in vivo, ex vivo and in vitro studies have significantly advanced our understanding of the mechanisms by which NPs may cause neurotoxicity and neurodegeneration. In light of this understanding, various pathways have been identified as the basic mechanisms by which NPs cause damage in the brain. The goal of this review is to summarize new mechanistic findings and different pathways of NP-induced neurotoxicity. Better knowledge of such pathways can lead researchers to devise effective therapeutic strategies for neuroprotection against nanoparticles.

Importance of magnetic nanoparticles in daily life including biomedical applications in near future cannot be overlooked. This review focuses on the properties of magnetic nanoparticles (MNPs), various approaches for their synthesis, and their biomedical applications. First part of this review focuses on the classes, physical properties, and characteristics of MNPs. The second part sheds light on strategies developed for the synthesis of MNPs, with special attention given to biological, physical, and chemical approaches as well as recent modifications in the preparation of monodispersed samples. Furthermore, this review deals with the biomedical applications of MNPs, which includes applications in targeted drug delivery, diagnostics, gene therapy, hyperthermia and advantages in the field of medicine.

In this paper, an extended review analysis has been presented concerning the developments in brain drug delivery through new and efficient applications of nanotechnology. Modern nanotechnological approaches for the diagnosis and treatment of Alzheimer's and Parkinson's diseases are described along with simultaneous analysis of safety and practical clinical usage of these strategies.

Prostate cancer is the fourth leading cause of mortality in Australian men. The prevalence and incidence is increasing in both developed and developing nations, thus there is a need for better screening and management of this disorder. While there is no direct known cause of prostate cancer, management is largely focused on early detection and treatment strategies. Of particular concern is advanced prostate cancer which can manifest as castrate resistant prostate cancer characterized by therapy resistance. This short review outlines the global epidemiology of prostate cancer, clinical manifestations, risk factors, current screening strategies including first line clinical screening as well as the use of circulating biomarkers, and treatment of prostate cancer through mainstream therapeutics as well as the cutting edge peptide and nano-technology based therapeutics that are being implemented or in the process of development to overcome therapeutic obstacles in the treatment of prostate cancer.

Despite extensive research for over two decades, the medical science is yet to assign the exact aetiology and mode of progression of Alzheimer's disease (AD). The modern era of AD drug development began with the proposal of the cholinergic hypothesis of memory impairment. Since then, despite the proposal and phase trials of many therapeutic options, only few drugs have shown some efficacy and safety. The reasons behind this have been many including the ineffectiveness of tested drugs and inadequacy of clinical development methods. In this manuscript, we present an account of modern structural, functional and molecular imaging developed for AD therapy. A comprehensive review of all the current and future treatment options for AD, ranging from cholinergic drugs, NMDA receptor antagonist, immunotherapy, drugs reducing Aβ production, and drugs targeting tau protein and mitochondrial dysfunction has also been provided. However, the failure of all the proposed treatment options to provide a complete cure of AD has been pushing for the need of new therapies. The recent advent of nano-drugs has been proposed to provide crucial breakthroughs in AD therapy. Hence, a detailed outline of the usage and applications of nano-drugs in AD therapy, and outstanding developments in nanodrug metabolism and disposition has been discussed.