Current Pharmaceutical Design - Volume 21, Issue 42, 2015

Functionalized magnetic nanoparticles followed two main directions in the field of biomedical applications: one direction is as image enhancing agents for magnetic resonance imaging (MRI) and the other is as drugdelivery devices for various biologically-active substances. A third field which just emerges in nanomedicine is the field of the so-called theranostic devices which combines in the same delivery vehicle both the therapeutic agent and the contrast substance. The advantages of using nanoparticles instead of larger carriers for delivery of both drug and image contrast enhancing agents will be highlighted throughout this review article. Despite the ever increasing number of articles reporting both in vitro and in vivo studies carried out on functionalized magnetic nanoparticles and envisaging their potential biomedical applications, only few formulations reached the phase of clinical trials and even fewer became marketed products. The perspectives in the field are open, since new drugs require new delivery devices and possibly new means of functionalization. At the same time, the field of nanomedicine also provides the opportunity to better exploit drugs that are already in clinical use by improving their bioavailability through appropriate nanoformulations.

Some of the most dangerous diseases of the eye are related to the posterior segment. Diseases such as age-related macular degeneration, cytomegalovirus retinitis, diabetic retinopathy, posterior uveitis and retinitis pigmentosa are difficult to treat using classical methods because of the many internal barriers of the eye which affect the drug efficiency. In this review, we will summarize the main research directions in the field of medicamentous treatment of posterior eye disorders belonging to the controlled drug delivery concept. The review is starting with the most important knowledge regarding anatomy and pathology of the posterior segment of the eye and is continuing with the current treatment methods of the eye posterior segment illnesses and drawbacks of these methods, the drugs administration pathways to the posterior segment of the eye. The last three sections present the state of the art regarding the latest discoveries including the commercial products in the modern drug delivery systems; the main classes of materials treated in the present review are implants, hydrogels and nano- microparticulate systems.

Cardiovascular diseases are the major cause of non-communicable illness in both developing and developed nations, representing 30% of global deaths. New therapeutic approaches are desperately needed. Nanomedicine represents one such approach, and involves using molecular entities on the scale of 10-150 nanometers, for purposes of diagnosing, treating, and preventing disease. This review provides a basic overview of nanotechnology, then reviews specific applications of nanotechnology to cardiovascular diseases. Most research has focused on diagnosing and treating atherosclerosis using nanoparticles (NPs). However, researchers are beginning to study NPs for use in acute coronary syndromes, revascularization procedures, and heart failure. Antimicrobial NPs directed at biofilms likely have applicability to identifying and treating endocarditis. Despite the large disease burden of cardiovascular diseases, there are fewer researchers and less funding being applied to this research. Additional investment in NP therapies would pay great dividends once these therapies come of age.

Gene delivery, a process of introducing foreign functional nucleic acids into target cells, has proven to be a very promising tool for inducing specific gene expression in host cells. Many different technologies have been developed for efficient gene delivery. Among them, electroporation has been adopted in gene delivery for decades, and it is currently widely used for transfection of different types of cells. Despite of the success achieved by bulk electroporation (BEP) for gene delivery in vitro and in vivo, it has significant drawbacks such as unstable transfection efficacy and low cell viability. In recent years, there is an emerging interest in understanding how individual cell accepts and responds to exogenous gene materials using single cell based micro-/nano-electroporation (MEP/NEP) technologies. In this review, the authors provide an overview of the recent development of MEP/NEP and their advantages in gene delivery. Additionally, the future perspectives of gene delivery with the application of electroporation are discussed.

Over the past two decades nanosizing technology has become one of the most successful formulation approaches for improving the bioavailability of poorly soluble drugs, which show a low oral absorption due to low dissolution velocity. Nanocrystals are nanoparticles of pure drug, without any matrix material, with an average diameter below 1 μm (typically in the range of 200-500 nm), which can be prepared in both water and non-water media as colloidal nanosuspensions stabilized using surfactants or polymers. The reduction of the drug particle diameter below 1 μm increases the dissolution velocity by increasing the particle surface and decreasing the diffusion layer thickness. Nanosuspension production processes involve two different approaches such as bottom-up (drug nanocrystal precipitation) and top-down (drug particle disintegration) technologies or a combination of two. Within these main approaches, a variety of possible techniques to achieve particle size reduction have been proposed by different research groups from both industry and academia. Even though nanosuspensions formulations have been especially studied for oral and parenteral administration, nanocrystals have showed a great potential also for topical delivery through alternative routes such as dermal, pulmonary and ocular route. The purpose of this review is to describe the main technologies used to produce nanosuspensions as well as to explore the most significant results and progresses obtained by application of drug nanocrystal formulations through topical routes.

Osteosarcoma is the most frequent primary bone tumor in the pediatric age group. Its aggressive local growth pattern and its high propensity to metastasize, mainly to the lungs, give the disease an unfavorable prognosis that has situated this disease as one of the leading causes of pediatric cancer death. Current protocols for osteosarcoma treatment are based on neo-adjuvant (pre-operatory) chemotherapy followed by surgical resection of the tumor and a new phase of adjuvant chemotherapy. Despite the progress that these protocols have made in improving the outcome of the disease, the limited access of drugs to bone tumor and metastases, their indiscriminate distribution in the organism, the high required doses that cause intolerable toxicity and the development of multidrug resistance, still represent a major challenge. Nanotechnology has emerged as a new strategy to successfully address these problems by the development of nanoscaled drug carriers that present the ability to target the drug to the tumor cells, achieving high drug concentrations in the tumor area, while decreasing its presence in healthy tissues and therefore its potential systemic toxicity. This review summarizes the different lipid nanocarriers developed to deliver first and second-line anti-osteosarcoma drugs as well as emerging agents in the treatment of this disease. Moreover, it also discusses the potential of these nanocarriers for the treatment of osteosarcoma.

The paper focuses on the advances in the field of pain treatment by transdermal delivery of specific drugs. Starting from a short description of the skin barrier, the pharmacodynamics and pharmacokinetics including absorption, distribution, action mechanism, metabolism and toxicity, aspects related to the use of pain therapy drugs are further discussed. Most recent results on topical anesthetic agents as well as the methods proved to overcome the skin barrier and to provide efficient delivery of the drug are also discussed. The present review is proposing to summarize the recent literature on the pharmacotherapeutic principles of local anesthetics and non-steroidal anti-inflammatory drugs, generally used to alleviate pain but also the drugs as nanoformulations with potential applications in transdermal delivery. A special attention is given to efficient formulations meant for transdermal penetration enhancement of anesthetics where the drug is encapsulated into macrocyclic molecules (cyclodextrins, cyclodextrin derivatives), liposomes or polymer nanoparticles and hydrogels.

There is a tremendous progress in the design and synthesis of nano-scaled, non-viral carriers in the previous two decades. The nanodelivery systems can significantly improve biopharmaceutical features, pharmacokinetic properties and therapeutic efficacy of entrapped drugs. Branched polyethylenimine (PEI) is a cationic polymer that contains primary, secondary and tertiary amino groups. Such type of water-soluble polymer having high density of amines is one of the most promising cationic vectors for gene delivery. Hence, constructing nanocarriers that contain PEI have attracted much research effort in gene therapy because of the synergy effects of PEI molecules for their efficient transfection and the multi-functionality of nanoparticles in delivery. In this review, we focus on the recent development on the design and synthesis of four types of PEI-based nanocarriers: 1) PEI-based polymeric micelles systems; 2) PEI-based polymeric nanoparticle system; 3) PEI/silica nanoparticle systems; and 4) PEI/metal nanoparticle systems. Their in vitro gene transfaction and in vivo gene therapy will be also discussed. Results from these studies have demonstrated that PEI-based nanocarriers are promising delivery systems because of their efficient gene transfection, negligible toxicity, capability to co-deliver nucleic acids and chemotherapy drugs, ease of modification with the targeting molecules, and good responsiveness to external stimulus.

Chemotherapy is the major and most widely used therapeutic strategy for the treatment of a wide variety of cancers. The non-specific/non-targeted drug delivery in chemotherapy leads to undesired side effects in normal and healthy tissues, and insufficient dosages to kill cancerous cells. Now-a-days, smart and intelligent multifunctional targeted nanomedicines based on various nanocarriers (dendrimers, carbon nanotubes, graphene, nanoparticles, quantum dots, self-emuslifying lipidic systems and carbon nanohorns etc) are being investigated promisingly in cancer treatment. In this article, we review the role of smart and intellegent multifucntional nanocarriers in delivery of chemotherapeutic agents with the aim to develop promising treatment strategy to combat with one of the killer of man kind i.e. cancer.

Ceramic nanoparticles are primarily made up of oxides, carbides, phosphates and carbonates of metals and metalloids such as calcium, titanium, silicon, etc. They have a wide range of applications due to a number of favourable properties, such as high heat resistance and chemical inertness. Out of all the areas of ceramic nanoparticles applications, biomedical field is the most explored one. In the biomedical field, ceramic nanoparticles are considered to be excellent carriers for drugs, genes, proteins, imaging agents etc. To be able to act as a good and successful drug delivery agent, various characteristics of nanoparticles need to be controlled, such as size range, surface properties, porosity, surface area to volume ratio, etc. In achieving these properties on the favourable side, the method of preparation and a good control over process variables play a key role. Choosing a suitable method to prepare nanoparticles, along with loading of significant amount of drug(s) leads to development of effective drug delivery systems which are being explored to a great extent. Ceramic nanoparticles have been successfully used as drug delivery systems against a number of diseases, such as bacterial infections, glaucoma, etc., and most widely, against cancer. This review gives a detailed account of commonly used methods for synthesising nanoparticles of various ceramic materials, along with an overview of their recent research status in the field of drug delivery.

The state-of-the-art in the investigation of drugs release from Silica-based ordered Mesoporous Materials (SMMs) is reviewed. First, the SMM systems used like host matrixes are described. Then, the model drugs studied until now, including their pharmacological action, structure and the mesoporous matrix employed for each drug, are comprehensively listed. Next, the factors influencing the release of drugs from SMMs and the strategies used to control the drug delivery, specially the chemical functionalization of the silica surface, are discussed. In addition, how all these factors were gathered in a kinetic equation that describes the drug release from the mesoporous matrixes is explained. The new application of molecular modeling and docking in the investigation of the drug delivery mechanisms from SMMs is also presented. Finally, the new approaches under investigation in this field are mentioned including the design of smart stimuli-responsive materials and other recent proposals for a future investigation.

Synthetic and biological vesicular carriers have been recognized as attractive and intelligent systems for delivery of a verity of bioactive molecules. The importance of such delivery systems can be mostly due to their physicochemical properties, i.e. a lipid bilayer surrounding an aqueous core which allows encapsulation and protection of active hydrophilic molecules such as nucleic acids. Synthetic vesicles such as liposomes have been studied as gene delivery systems for decades. However, due to their fast clearance, toxicity and immunogenicity which impose restrictions on clinical applications, some other natural lipid vesicles such as exosomes have been considered as alternatives. Attractive features of nature's own ‘nano-vesicles’ such as exosomes, virosomes, bacterial ghosts and erythrocyte ghosts include efficient cellular entry, physicochemical properties and evading immune responses. Nevertheless, there are advantages and disadvantages with both synthetic and biological vesicular systems. Here, we provide an overview into different vesicle-based gene delivery systems and discuss how various modifications in their structure and formulations could improve the transfection efficiency and decrease the toxicity.

Nano drug delivery systems (NDDSs) have been widely used in tumor-targeted therapy since they can effectively reduce the side effects of traditional antitumor drugs and improve the anti-tumor effect. We divided the in vivo process of tumor-targeted NDDSs into seven steps: blood circulation, tumor accumulation, tumor tissue penetration, target cells internalization, lysosome escape, drug release and drug response. In each step, NDDSs will encounter different types of barriers preventing their effective delivery or response. The researchers have been making efforts to find different strategies of overcoming the corresponding barriers for NDDSs. Hence, we here reviewed the recent progress of NDDSs in breaking the physiological barriers for more effective in vivo anti-tumor effect, in order to shed a new perspective on the development of tumor-targeted NDDSs.

Medical devices form a broad range of appliances from a basic nanoparticle coating or surgical gloves to a complicated laser therapy device. These devices are designed to support patients, surgeons and healthcare personnel in meeting patients’ healthcare needs. Regulatory authorities of each country regulate the process of approval, manufacturing and sales of these medical devices so as to ensure safety and quality to patients or users. Recent recalls of medical devices has increased importance of safety, awareness and regulation of the devices. Singapore and India have strong presence and national priorities in medical devices development and use. Herein we capture the rationale of each of these national regulatory bodies and compare them with the medical devices regulatory practices of USA and European nations. Apart from the comparison of various regulatory aspects, this review will specifically throw light on the polymer material based medical devices and their safety.

Tumor metastasis is an important prognostic factor regarding long-term survival rate of cancer patients. At present, no imaging modality or technique is ideal for diagnosis of metastases. Molecular imaging has provided a fantastic tool for tumor metastases imaging. Based on the current medical imaging tools such as magnetic resonance imaging (MRI), optical, single-photon emission computed tomography (SPECT), and positron emission tomography (PET), various techniques and functional molecular probes for molecular imaging of tumor metastases have been developed. In this review, we will summarize the current status of nanoprobe based molecular imaging metastases in cancer.