Current Pharmaceutical Design - Volume 21, Issue 29, 2015

Nanoparticles have been extensively employed to deliver many drugs, including siRNA, for the treatment of a variety of diseases, particularly cancer. Lately, there has been a great deal of effort to design nanoparticles with materials that are able to respond to intrinsic or extrinsic stimuli for “on demand” delivery of siRNA. These nanoparticles are able to trigger siRNA release upon different stimuli, such as a pH decrease, redox gradient, enzyme, light, magnetic field, temperature, ultrasound or electric current. Frequently, the stimuli cause the nanoparticles to undergo protonation, hydrolytic breakdown or phase transition for triggered release of siRNA, resulting in decreased side effects and better therapeutic outcome. While studies have demonstrated efficient in vitro and in vivo delivery, these “smart” nanoparticles have not yet reached the clinic. In this review, we address different classes of nanoparticles, such as polyplexes, lipoplexes, liposomes, polymeric micelles, polymeric, lipid and inorganic nanoparticles, that are able to respond to specific stimuli for siRNA triggered-release, emphasizing their application and discussing the latest advances.

Organic and inorganic nanoparticles show great potential for cancer diagnosis and treatment. Because gastric cancer (GC) represents the second most deadly type of neoplasia worldwide, continued research efforts by scientists and clinicians are essential to improve diagnosis and treatment. This paper reviews significant findings in the area of nanoparticles (organic and inorganic origin) that may aid in prevention and diagnosis of GC. This review focuses in the first section on H. pylori and the connection to GC, highlighting nanoformulations designed to control bacterial growth. The second section evaluates the potential of different imaging techniques (especially using inorganic nanoparticles) in the detection of GC, and the third section summarizes how nanotechnology may be employed in the analytical detection of GC biomarkers (metallic plasmons, electrochemical biosensors and colorimetric sensors). We foresee that the prevention and diagnosis of GC will require the development of complex collaborative studies. Additionally, scientists also need to be tightly connected to industry in order to facilitate upscaling and rapid transfer of promising products to the clinic.

The advent of recombinant DNA technology and computational designing has fueled the emergence of proteins and peptides as a new class of modern therapeutics such as vaccines, antigens, antibodies and hormones. Demand for such therapeutics has increased recently due to their distinct pharmacodynamic characteristics of specificity of action and high potency. However, their potential clinical applications are often hindered by involvement of factors which impact their therapeutic potential negatively. Large size, low permeability, conformational fragility, immunogenicity, metabolic degradation and short half-life results in poor bioavailability and inferior efficacy. These challenges have encouraged researchers to devise strategies for effective delivery of proteins and peptides. Recent advances made in nanotechnology are being sought to overcome aforesaid problems and to offer advantages such as higher drug loading, improved stability, sustained release, amenability for non-parenteral administration and targeting through surface modifications. This review focuses on elaborating the role of nanotechnology based formulations and associated challenges in protein and peptide delivery, their clinical outlook and future perspective.

Nanotechnology and nanomedicine provide a platform for advanced therapeutic strategies for dermal and transdermal drug delivery. The focus of this review is on the current state-of-art in lipid-based nanotechnology and nanomedicine for (trans)dermal drug therapy. Drug delivery nanosystems based on the (phospho)lipid constituents are characterized and compared, with the emphasis on their ability to assure the controlled drug release to the skin and skin appendages, drug targeting and safety. Different types of liposomes, biphasic vesicles, particulate lipid-based nanosystems and micro- and nano-emulsions are discussed in more details. Extensive research in preclinical studies has shown that numerous parameters including the composition, size, surface properties and their combinations affect the deposition and/or penetration of carrier-associated drug into/through the skin, and consequently determine the therapeutic effect. The superiority of the most promising nanopharmaceuticals has been confirmed in clinical studies. We have selected several common skin disorders and provided overview over promises of nanodermatology in antimicrobial skin therapy, anti-acne treatment, skin oncology, gene delivery and vaccines. We addressed the potential toxicity and irritation issues and provided an overview of registered lipid-based products.

Gene therapy, currently, represents one of the new therapies that have emerged for the treatment of different diseases. Between the different approaches that can be chosen concerning this therapy, gene delivery with non-viral systems has focused the attention during the past decades, because of the reduced toxicity compared to the viral systems. Non-viral vectors are formed by a group of different molecules with a wide variety of sources and features. Among them, polymeric systems have been extensively studied due to the ability to form nanoparticles in the presence of nucleic acids, protect the included nucleic acid and more importantly, improve the entrance of the desired nucleic acid fragment into the cell and hopefully achieve a therapeutic effect. In this review, some of the most used polymeric systems are commented with the main characteristics that can influence the activity of each of them, such as the molecular weight, N/P ratio (positive charges of cationic polymer/negative charges of pDNA), stability or the molecular structure.

Immunotherapy of cancer is a promising therapeutic approach which aims to eliminate malignancies by inducing or enhancing an immune response against the tumor. Immunotherapy, however, faces several challenges such as local immunosuppression in the tumor area leading to immunological tolerance. To overcome these challenges, particulate formulations such as nano- and microparticles containing immunotherapeutics have been developed to increase therapeutic efficacy and reduce toxicity of immunotherapy. Particulate formulations based on biodegradable aliphatic polyesters such as poly(lactic-co-glycolic acid) (pLGA) have been extensively used with promising results. In this review, we addressed the potential of pLGA-based particulate formulations for immunotherapy of cancer. The discussion was focused on cancer vaccines and delivery of immunomodulatory antibodies. Features and drawbacks of pLGA systems were discussed together with several examples of recently developed therapeutic cancer vaccines and antibody-loaded particulate systems. Various strategies to overcome the drawbacks and optimize the formulations were given. In conclusion, pLGA-based particulate systems are attractive carriers for development of clinically acceptable formulations in immunotherapy of cancer.

Many new developed drug actives are poorly soluble, therefore the need to increase the solubility of these actives arises. Nanosuspensions are fast and easy to produce, enhance the bioavailability of poorly soluble drugs and feature many beneficial characteristics. However, nanocrystals in suspension form are physically metastable. Furthermore, the application of nanocrystal suspensions has no retarding effects. To overcome long term stability issues and open up a variety of options for controlled release, nanocrystals can be converted into solid dosage forms by different methods with different outcomes and features. Transformation of nanosuspensions into solid dosage forms opens up manifold options for the development of dosage forms with tailor-made drug release profiles. This review focuses on nanocrystal properties, established and new production techniques, as well as state of the art techniques for transformation of nanosuspensions into solid dosage forms. Nanocrystal technology is already today used in several solid products and holds great potential for future uses.

Allergen specific immunotherapy has been introduced in the clinic more than 100 years ago showing effectiveness and, so far, it represents the only curative approach to treat allergic disorders ameliorating the symptoms, reducing the medication costs and blocking the onset of new sensitizations. However, some questions are still open regarding to the safety of the treatment and the need to reduce the dose and time of administration to improve the compliance of the patients. All preparations that are currently available may trigger side effects. For these reasons, new formulations and route of administration have been exploited demonstrating that such products presented improved efficacy and safety. Nanotechnology for biomedical applications offers many advantages, such as improved stability and bioavailability, favourable biodistribution profiles and targeting to specific cell populations whose impact on the immune system has been evaluated in animal systems. Nanoparticles interact with the immune system, and the final outcome of this interaction depends on their physico-chemical characteristics. Concerns can be raised when immunotoxic effect are induced, resulting in inflammatory dangerous responses or in the reduction of the normal defensive activity of the immune system. In this paper, we will review the most relevant data about the synthesis of allergen/nanoparticles systems and will discuss their impact on the immune system in terms of immunomodulatory activity and immunotoxicity risk assessment.

Gold –based nanoparticles are utilized for cancer therapeutics as a system for drug delivery, or as a mediator for thermal therapy, whether ablation or hyperthermia. This review discusses how the design of the physicochemical properties of the different types of gold-based nanoparticles affects their treatment efficacy. The basic principles and mechanism at which it mediates heating and delivers drugs efficiently in vivo is also summarized. We will also review the in vivo preclinical data on the biodistribution, intratumoral distribution, cell internalization, and its associated toxicity. Lastly, an updated list of the clinical trials based on nanoparticles and future perspectives are provided.

Nanotoxicology deals with the new perception regarding nanotechnology i.e. risk and hazards associated with nanoscale materials. Although, nanotechnology is playing significant role in modern advancements from cell phones to medicines, yet it is necessary to consider their negative part as well that could be dangerous if not given proper attention. It is not certain that nanotechnology will essentially exert toxic effects since at present only few reports are available on their toxic effects and most of them are controversial. In this review we have summarized the advances in nanotechnology, their applications and, most importantly their safety issues that are often overlooked. However combined efforts are advocated to develop promising regulatory and ethical guidelines to control production, use and disposal of nanomaterials that will be safe to human health, environment and other living organisms.

In the past few decades, the applications of nanomaterials in biologic systems have become one of the most studied areas. Many novel syntheses and processing methods have been developed to generate nanomaterials to enhance biomedical applications. Among those methods, polydopamine (PDA) integrated nanomaterials have attracted considerable interest for various types of biomedical applications. This concise review outlines the basic chemistry and material science regarding PDA and discusses its successful applications in drug delivery, biosensing, antifouling and antimicrobial activities, as well as its interaction with cells.

Applications of polymeric nanotechnologies for enabling therapies for cardiovascular diseases have shown recent success. Both intravenous and oral administration have been investigated and achieved different degrees of development. While circulating polymeric nanostructured carriers are subjected to a number of interactions, smart nanoparticle design has enabled the formulation of active molecules to be delivered to specific targets for cardiovascular effects. This review aims at outlining the multiple factors that can affect the fate of polymeric nanostructured carriers in systemic circulation. With an understanding of these factors, the literature on the various polymeric nanostructured carriers is reviewed. Finally, the emerging uses of nanotechnology to formulate orally administered drugs for cardiovascular diseases are depicted.

Chitosan on its own is a well-established natural polymer and is widely regarded as a biodegradable, biocompatible and nontoxic material for drug delivery applications. Although unmodified chitosan has some mucoadhesive properties on its own, its bioavailability is limited due to its short retention time in the body. Moreover, the high solubility of chitosan at acidic pH levels limits its use for mucosal drug delivery (especially through the oral route). Chemically-modified mucoadhesive chitosan, especially thiolated chitosan, has arisen as an alternative to create novel mucosal drug delivery systems. The mucoadhesive properties that are conferred to the thiolated chitosan certainly set this novel class of second or third-generation thiomers apart. To understand the significance of mucoadhesive chitosan, we first present the mechanism of mucoadhesion and provide comprehensive coverage of description of a variety of chemical modifications to prepare mucoadhesive thiolated chitosan derivatives. We then present the plethora of applications of these modified chitosan variants in a wide range of drug delivery fields, including the delivery of antigens, proteins and genes through a variety of routes, including oral, nasal, pulmonary, vaginal and others. By presenting the range of applications for mucoadhesive chitosan drug carriers we herein demonstrate that chemically-modified thiolated chitosan is a versatile and effective material for a new class of drug delivery vehicles.

Small interfering RNAs (siRNA) are emerging as a new opportunity for treatment of various diseases, including viral and cancer diseases via knocking down a specific gene that involves in disease development. But their clinical application is hampered because of susceptibility to degradation and difficult delivery of siRNA into cells. So it is needed to develop an efficient carrier that stabilizes and delivers siRNA efficiently and specifically into cells. Hollow inorganic nanoparticles have gained considerable attention as an efficient drug and gene delivery system. This is due to their biocompatibility, simple preparative processes, easy functionalization and high capacity for drug loading. Several nanoparticle platforms for siRNA delivery have been developed to overcome the major limitations facing the therapeutic uses of siRNA. Recently, researchers have developed a wide range of inorganic nanocarriers to increase efficacy of si-RNA-based drugs and gained efficient siRNA delivery both in vitro and in vivo. This review covers a broad spectrum of hollow inorganic nanoparticles as non-viral siRNA delivery systems. These nanoparticles are developed for enhanced cellular uptake and targeted gene silencing in vitro and in vivo and their characteristics and opportunities for clinical applications of therapeutic siRNA are discussed in this article. Various types of inorganic hollow nanovectors including: mesoporous silica nanoparticles, carbon nanotubes, graphene oxide, fullerenes, calcium phosphate nanoparticles, hollow manganese oxide, gold nanoshells, and layered double hydroxide nanoparticles used to deliver siRNA are introduced and the development of theranostics and combinational treatment is also discussed.

The treatment of skin wounds represents an important research area due to the important physiological and aesthetic role of this tissue. During the last years, nanoparticles have emerged as important platforms to treat skin wounds. Silver, gold, and copper nanoparticles, as well as titanium and zinc oxide nanoparticles, have shown potential therapeutic effects on wound healing. Due to their specific characteristics, nanoparticles such as nanocapsules, polymersomes, solid lipid nanoparticles, and polymeric nanocomplexes are ideal vehicles to improve the effect of drugs (antibiotics, growth factors, etc.) aimed at wound healing. On the other hand, if active excipients are added during the formulation, such as hyaluronate or chitosan, the nanomedicine could significantly improve its potential. In addition, the inclusion of nanoparticles in different pharmaceutical materials may enhance the beneficial effects of the formulations, and allow achieving a better dose control. This paper aims at reviewing significant findings in the area of nanoparticles and wound treatment. Among the reviewed topics, we underline formulations comprising inorganic, polymeric, surfactant self-assembled, and lipid nanosystems. Among the drugs included in the nanoformulations, the paper refers to antibiotics, natural extracts, proteins, and growth factors, among others. Finally, the paper also addresses nanoparticles embedded in secondary vehicles (fibers, dressings, hydrogels, etc.) that could improve their application and/or upgrade the release profile of the active.

Molecular hydrogels have been widely explored in various biomedical applications, such as cell culture, tissue engineering and drug delivery. Peptide-based hydrogel nanoparticles represent a promising alternative to current drug delivery approaches and cell carriers for tissue engineering, due to their encapsulation stability, water solubility and biocompatibility. This review focuses on recent advances in the use of self-assembling peptide nanogels for applications in drug delivery. We firstly introduce a self-assembly mechanism for small molecules used in the peptide hydrogel, and then describe recent methods for controlling the assembly of molecular hydrogelations. A particular emphasis is placed on recent advances in the use of different types of peptide hydrogels as drug delivery carriers. Lastly, the current challenges and future perspectives for self-assembling peptide hydrogels in drug delivery applications are discussed.

A large amount of new drug candidates are practically insoluble in aqueous solvents and are even simultaneously poorly soluble in organic solvents. Nanosuspension drug delivery system (DDS) was firstly developed in 1994 and has attracted more and more attention as a formation solution for the poorly soluble drugs. By nansizing the poorly soluble drugs, nanosuspensions have several outstanding advantages for drug delivery. Among many administration routes of drug delivery, oral administration is the most preferred route due to its advantages such as ease of ingestion, versatility to accommodate various types of drug candidates, low production cost, high safety, good patient compliance, and pain avoidance. Current marketed pharmaceutical nanosuspension DDS products are mostly for oral administration. This review is to systematically summarize the nanosuspension DDS dosage form developments of poorly soluble drugs for oral administration use.