Current Drug Targets - Volume 19, Issue 3, 2018

Background: Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Objective: Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Results: Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. Conclusion: The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers.

Background: Cancer is one of the major leading causes of death worldwide and its prevalence will be higher in the coming years due to the progressive aging of the population. The development of nanocarriers in oncology has provided a new hope in the fight against this terrible disease. Objective: Among the different types of nanoparticles which have been reported in the scientific literature, mesoporous silica nanoparticles (MSNs) are very promising materials due to their inherent properties such as high loading capacity of many different drugs, excellent biocompatibility and easy functionalization. Results: This review presents the current state of the art related to the development of mesoporous silica nanocarriers for antitumoral therapy paying special attention on targeted MSN able to selectively destroy tumoral cells, reducing the side damage in healthy ones, and the basic principles of targeting tumoral tissues and cells. Conclusions: MSNs constitute a promising nanomaterial for drug delivery applications in antitumoral therapy as a consequence of its unique properties such as excellent biocompatibility, high loading capacity, robustness, easy production and existence of multiple strategies for their functionalization with a myriad of bio-organic moieties. In the coming years, the clever application of this material would provide novel alternatives for the treatment of this complex disease.

Background: Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. Objective: The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Results: Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Conclusion: Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world.

Background: In the last years, the production and applications of nanoparticles based on iron oxides in the field of biomedicine presented a great interest due to their particular properties. Because of the expansion of the pharmaceutical industry numerous new systems for drugs delivery have appeared, and those centered on magnetic nanoparticles are in a particular attention and in different promising developmental stages. Objective: In this mini review, some representative, interesting and feasible magnetic nanostructures obtained recently (from last 5-6 years) with possible use in antitumor/anticancer therapy are presented. Results: The synthesis of these nanostructures with magnetic properties implies very simple assembling procedures and presents one of the lowest cytotoxic profiles. Magnetic nanostructures displayed possible appliance in a large diversity of biotechnological and medical fields, both for diagnose and therapy. Conclusion: Different types of magnetic nano-carriers loaded with different antitumor/anticancer agents and the cases tested in vivo are considered.

Background: The search for smart delivery systems for enhanced pre-clinical and clinical pharmaceutical delivery and cell targeting continues to be a major biomedical research endeavor owing to differences in the physicochemical characteristics and physiological effects of drug molecules, and this affects the delivery mechanisms to elicit maximum therapeutic effects. Targeted drug delivery is a smart evolution essential to address major challenges associated with conventional drug delivery systems. These challenges mostly result in poor pharmacokinetics due to the inability of the active pharmaceutical ingredients to specifically act on malignant cells thus, causing poor therapeutic index and toxicity to surrounding normal cells. Aptamers are oligonucleotides with engineered affinities to bind specifically to their cognate targets. Aptamers have gained significant interests as effective targeting elements for enhanced therapeutic delivery as they can be generated to specifically bind to wide range of targets including proteins, peptides, ions, cells and tissues. Notwithstanding, effective delivery of aptamers as therapeutic vehicles is challenged by cell membrane electrostatic repulsion, endonuclease degradation, low pH cleavage, and binding conformation stability. Objective: The application of molecularly engineered biodegradable and biocompatible polymeric particles with tunable features such as surface area and chemistry, particulate size distribution and toxicity creates opportunities to develop smart aptamer-mediated delivery systems for controlled drug release. Results: This article discusses opportunities for particulate aptamer-drug formulations to advance current drug delivery modalities by navigating active ingredients through cellular and biomolecular traffic to target sites for sustained and controlled release at effective therapeutic dosages while minimizing systemic cytotoxic effects. Conclusion: A proposal for a novel drug-polymer-aptamer-polymer (DPAP) design of aptamer-drug formulation with stage-wise delivery mechanism is presented to illustrate the potential efficacy of aptamer- polymer cargos for enhanced cell targeting and drug delivery.

Background: Liposomes are vesicular carriers which possess aqueous core entrapped within the lipid bilayer. These are carriers of choice because of biocompatible and biodegradable features in addition to flexibility of surface modifications at surface and lipid compositions of lipid bilayers. Objective: Liposomes have been reported well for cancer treatment using both passive and active targeting approaches however tumor microenvironment is still the biggest hurdle for safe and effective delivery of anticancer agents. To overcome this problem, stimuli-responsive smart liposomes have emerged as promising cargoes pioneered to anomalous tumor milieu in response to pH, temperature, and enzymes etc. as internal triggers, and magnetic field, ultrasound, and redox potential as external guides for enhancement of drug delivery to tumors. Conclusion: This review focuses on all such stimuli-responsive approaches using fabrication potentiality of liposomes in combination to various ligands, linkers, and PEGylation etc. Scientists engaged in cancer targeting approaches can get benefited greatly with this knowledgeable assemblage of advances in liposomal nanovectors.

Background: Efforts in developing various colloidal nanoparticles (NPs) as theranostic probes have been promising in the biomedical field. Specifically, colloidal gold nanoparticles (GNP) have been extensively utilized as a theranostic probe for molecular imaging and drug delivery owing to their unique physiochemical properties with excellent biocompatibility. Objective: This review outlines and discusses the progress regarding gold nanoparticle synthesis methods for controlled geometry (spherical, rod, and cage), surface functionalization (covalent and non-covalent), and associated in vitro/in vivo cytotoxicity as well as some of the interesting diagnostic (imaging) and therapeutic (photo-thermal, drug delivery) applications. Results and Conclusion: GNP possesses several advantages compared to other traditional theranostic agents, we firmly believe that GNP based clinical approach will gain continuous interest with increasing numbers of innovations.

Background: Stem cell therapy provides great promising therapeutic benefits for various neurological disorders. Cell transplantation has emerged as cell replacement application for nerve damage. Recently, nanomaterials obtain wide development in various industrial and medical fields, and nanoparticles have been applied in the neurological field for tracking and treating nervous system diseases. Combining stem cells with nanotechnology has raised more and more attentions; and it has demonstrated that the combination has huge effects on clinical diagnosis and therapeutics in multiple central nervous system diseases, meanwhile, improves prognosis. Objective: The aim of this review was to give a brief overview of the application of nanomaterials in stem cell therapy for neurological diseases. Results: Nanoparticles not only promote stem cell proliferation and differentiation in vitro or in vivo, but also play dominant roles on stem cell imaging and tracking. Furthermore, via delivering genes or drugs, nanoparticles can participate in stem cell therapeutic applications for various neurological diseases, such as ischemic stroke, spinal cord injury (SCI), multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD) and gliomas. However, nanoparticles have potential cytotoxic effects on nerve cells, which are related to their physicochemical properties. Conclusion: Nano-stem cell-based therapy as a promising strategy has the ability to affect neuronal repair and regeneration in the central nervous system.