Drug delivery/imaging multifunctionality of mesoporous silica-based composite nanostructures

Introduction: Biocompatible mesoporous silica nanoparticles (MSNs) are regarded as one of the most promising inorganic drug delivery systems (DDSs) to concurrently enhance the therapeutic efficiency and mitigate the side effects of anticancer drugs. Elaborately combining multicomponents with MSNs will endow them with specific functionalities for cancer therapy and diagnosis, such as targeted drug delivery, intelligent on-demand drug releasing, synergistic therapy, diagnostic imaging and so on.

Areas covered: This review discusses the state-of-the-art potential obstacles and further perspectives of the chemical design/synthesis, in vitro/in vivo pharmaceutical evaluations and potential clinical translations of multifunctional mesoporous silica-based nanomaterials for biotechnological and biomedical applications, especially against cancer. These topics cover the years from 2001 to 2013.

Expert opinion: Through the comprehensive evaluations of the biosafety and pharmaceutical efficiency, elaborately designed/fabricated mesoporous silica-based composite nanoparticles show great potentials in clinical applications for efficient diagnostic imaging and chemotherapy of cancer.     

Stimuli-responsive nanoscale drug delivery systems for cancer therapy

Abstract

Currently, with the rapid development of nanotechnology, novel drug delivery systems (DDSs) have made rapid progress, in which nanocarriers play an important role in the tumour treatment. In view of the conventional chemotherapeutic drugs with many restrictions such as nonspecific systemic toxicity, short half-life and low concentration in the tumour sites, stimuli-responsive DDSs can deliver anti-tumour drugs targeting to the specific sites of tumours. Owing to precise stimuli response, stimuli-responsive DDSs can control drug release, so as to improve the curative effects, reduce the damage of normal tissues and organs, and decrease the side effects of traditional anticancer drugs. At present, according to the physicochemical properties and structures of nanomaterials, they can be divided into three categories: (1) endogenous stimuli-responsive materials, including pH, enzyme and redox responsive materials; (2) exogenous stimuli-responsive materials, such as temperature, light, ultrasound and magnetic field responsive materials; (3) multi-stimuli responsive materials. This review mainly focuses on the researches and developments of these novel stimuli-responsive DDSs based on above-mentioned nanomaterials and their clinical applications.     

The alluring potential of functionalized carbon nanotubes in drug discovery

Importance of the field: The possibility of carbon nanotube integration into living systems for therapeutic and diagnostic purposes has opened the way to explore their applications in drug delivery and discovery. A wide variety of chemical approaches has been developed to functionalize carbon nanotubes with therapeutic molecules towards different biomedical uses.

Areas covered in this review: This review covers the recent advances in the development of functionalized carbon nanotubes to offer improvements for different diseases, in particular for cancer therapy.

What the reader will gain: Functionalized carbon nanotubes are able to transport therapeutic agents. Targeted methodologies using carbon nanotube-based conjugates have been investigated to improve the efficacy of some drugs. The capacity of such nanomaterials to seamlessly translocate into cells with alternative various mechanisms and their pharmacokinetic properties is also discussed.

Take home message: Although at its infancy, functionalized carbon nanotubes are very promising as a new nanomedicine platform in the field of drug discovery and delivery. They have the capacity to cross biological barriers and can be eliminated via renal and/or fecal excretion. They can transport small drug molecules while maintaining – and in some cases improving – their therapeutic efficacy.     

Filled carbon nanotubes in biomedical imaging and drug delivery

Introduction: Carbon nanotubes have been advocated as promising candidates in the biomedical field in the areas of diagnosis and therapy. In terms of drug delivery, the use of carbon nanotubes can overcome some limitations of ‘free’ drugs by improving the formulation of poorly water-soluble drugs, allowing targeted delivery and even enabling the co-delivery of two or more drugs for combination therapy. Two different approaches are currently being explored for the delivery of diagnostic and therapeutic agents by carbon nanotubes, namely attachment of the payload to the external sidewalls or encapsulation into the inner cavities. Although less explored, the latter confers additional stability to the chosen diagnostic or therapeutic agents, and leaves the backbone structure of the nanotubes available for its functionalization with dispersing and targeting moieties. Several drug delivery systems and diagnostic agents have been developed in the last years employing the inner tubular cavities of carbon nanotubes.

Areas covered: The research discussed in this review focuses on the use of carbon nanotubes that contain in their interior drug molecules and diagnosis-related compounds. The approaches employed for the development of such nanoscale vehicles along with targeting and releasing strategies are discussed.

Expert opinion: The encapsulation of both biomedical contrast agents and drugs inside carbon nanotubes is further expanding the possibilities to allow an early diagnosis and treatment of diseases.     

Metal-organic frameworks for advanced drug delivery

Metal-organic frameworks (MOFs), comprised of organic ligands and metal ions/metal clusters via coordinative bonds are highly porous, crystalline materials. Their tunable porosity, chemical composition, size and shape, and easy surface functionalization make this large family more and more popular for drug delivery. There is a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications. This article presents an overall review and perspectives of MOFs-based drug delivery systems (DDSs), starting with the MOFs classification adapted for DDSs based on the types of constituting metals and ligands. Then, the synthesis and characterization of MOFs for DDSs are developed, followed by the drug loading strategies, applications, biopharmaceutics and quality control. Importantly, a variety of representative applications of MOFs are detailed from a point of view of applications in pharmaceutics, diseases therapy and advanced DDSs. In particular, the biopharmaceutics and quality control of MOFs-based DDSs are summarized with critical issues to be addressed. Finally, challenges in MOFs development for DDSs are discussed, such as biostability, biosafety, biopharmaceutics and nomenclature.     

Cell-specific aptamers and their conjugation with nanomaterials for targeted drug delivery

Introduction: Aptamers are short, single-stranded DNA or RNA sequences that can fold into complex secondary and tertiary structures and bind to various target molecules with high affinity and specificity. These properties, as well as rapid tissue penetration and ease of chemical modification, make aptamers ideal recognition elements for in vivo targeted drug delivery and attractive molecules for use in disease diagnosis and therapy.

Areas covered: The general properties of aptamers as well as advantages over their counterpart antibodies are briefly discussed. Next, aptamer selection by cell- systematic evolution of ligands by exponential enrichment is described in detail. Finally, the review summarizes recent progress in the field of targeted drug delivery based on aptamers and their conjugation to liposomes, micelles and other nanomaterials.

Expert opinion: Advances in nanotechnology have led to new and improved nanomaterials for biomedical applications. Conjugation of nanoparticles (NPs) with aptamers exploits both technologies, making aptamer-NP conjugates ideal agents for drug delivery with proven therapeutic effects and the reduction of toxicity to normal tissue. The use of multivalent aptamer-conjugated nanomaterials represents one of the new directions for drug development in the future; as such, continuing studies of these multivalent aptamers and bioconjugates should result in important clinical applications in targeted drug delivery.     

Drug delivery strategies for therapy of visceral leishmaniasis

Importance of the field: Visceral leishmaniasis (VL) is the most overwhelming type of leishmaniasis associated with the poverty of developing countries and usually mortal if untreated. Most of the conventionally used dosage forms offer us the shortcomings of toxic side effects and emergence of drug resistance. Several efforts have been made to overcome the barriers involved in the treatment of VL. Colloidal carriers extensively represent the drug delivery systems (DDSs) for intracellular localization of antileishmanial compounds in macrophage-rich organs such as liver, spleen and bone marrow. These DDSs offer superior therapeutic efficacy over the conventional treatment in terms of site-specific drug delivery with reduced side effects. However, after 35 years of research in the field, AmBisome^® (Amphotericin B liposome for injection, Astellas Pharma US, Inc.) is the only DDS used against the VL.

Areas covered in this review: A literature search was performed (for drugs and DDSs against VL) on PubMed and through Google.

What the reader will gain: This review aims to describe the pathophysiology of VL and its current conventional treatment with special reference to DDSs designed against VL.

Take home message: On reviewing the conventional drugs and DDSs developed against VL, it is concluded that advances in the field of targeted drug delivery can result in more efficient strategies for the therapy of VL.     

ROS-responsive drug delivery systems for biomedical applications

In the field of biomedicine, stimuli-responsive drug delivery systems (DDSs) have become increasingly popular due to their site-specific release ability in response to a certain physiological stimulus, which may result in both enhanced treatment outcome and reduced side effects. Reactive oxygen species (ROS) are the unavoidable consequence of cell oxidative metabolism. ROS play a crucial part in regulating biological and physiological processes, whereas excessive intracellular ROS usually lead to the oxidation stress which has implications in several typical diseases such as cancer, inflammation and atherosclerosis. Therefore, ROS-responsive DDSs have elicited widespread popularity for their promising applications in a series of biomedical research because the payload is only released in targeted cells or tissues that overproduce ROS. According to the design of ROS-responsive DDSs, the main release mechanisms of therapeutic agents can be ascribed to ROS-induced carrier solubility change, ROS-induced carrier cleavage or ROS-induced prodrug linker cleavage. This review summarized the latest development and novel design of ROS-responsive DDSs and discussed their design concepts and the applications in the biomedical field.     

Cellulose nanocrystals: a versatile nanoplatform for emerging biomedical applications

ABSTRACT

Introduction: Cellulose nanocrystals (CNCs) are bio-based nanomaterials typically derived from the acid hydrolysis of the most abundant natural polymer, cellulose. These nanomaterials have garnered significant interest due to their unique properties, such as uniform rod-like shape, high surface area, high strength, liquid crystalline behavior, tailored surface chemistry, biocompatibility, biodegradability, sustainability and non-toxic carbohydrate-based nature.

Areas covered: The recent developments in the use of unmodified and modified CNCs as versatile nanoplatforms for emerging biomedical applications such as drug delivery systems, enzyme/protein immobilization scaffolds, bioimaging, biosensing and tissue engineering are highlighted. A brief discussion of the biological and toxicity properties of CNCs is also presented.

Expert opinion: While a number of recent studies have indicated that CNCs are promising nanomaterials for biomedical applications, there is a substantial amount of work that still remains to be done before realizing the full therapeutic potential of CNCs. Major effort should be focused on detailed in vitro and in vivo studies of modified CNCs constructs in order to better understand the integration of CNCs in the biological systems.     

pH- and ion-sensitive polymers for drug delivery

Introduction: Drug delivery systems (DDSs) are important for effective, safe, and convenient administration of drugs. pH- and ion-responsive polymers have been widely employed in DDS for site-specific drug release due to their abilities to exploit specific pH- or ion-gradients in the human body.

Areas covered: Having pH-sensitivity, cationic polymers can mask the taste of drugs and release drugs in the stomach by responding to gastric low pH. Anionic polymers responsive to intestinal high pH are used for preventing gastric degradation of drug, colon drug delivery and achieving high bioavailability of weak basic drugs. Tumor-targeted DDSs have been developed based on polymers with imidazole groups or poly(β-amino ester) responsive to tumoral low pH. Polymers with pH-sensitive chemical linkages, such as hydrazone, acetal, ortho ester and vinyl ester, pH-sensitive cell-penetrating peptides and cationic polymers undergoing pH-dependent protonation have been studied to utilize the pH gradient along the endocytic pathway for intracellular drug delivery. As ion-sensitive polymers, ion-exchange resins are frequently used for taste-masking, counterion-responsive drug release and sustained drug release. Polymers responding to ions in the saliva and gastrointestinal fluids are also used for controlled drug release in oral drug formulations.

Expert opinion: Stimuli-responsive DDSs are important for achieving site-specific and controlled drug release; however, intraindividual, interindividual and intercellular variations of pH should be considered when designing DDSs or drug products. Combination of polymers and other components, and deeper understanding of human physiology are important for development of pH- and ion-sensitive polymeric DDS products for patients.     

Drug delivery for bioactive polysaccharides to improve their drug-like properties and curative efficacy

Abstract

Over several decades, natural polysaccharides (PSs) have been actively exploited for their wide bioactivities. So far, many PS-related reviews have been published; however, none focused on the delivery of bioactive PSs as therapeutic molecules. Herein, we summarized and discussed general pharmacokinetic properties of PSs and drug delivery systems (DDSs) developed for them, together with the challenges and prospects. Overall, most bioactive PSs suffer from undesirable pharmacokinetic attributes, which negatively affect their efficacy and clinical use. Various DDSs therefore have been being utilized to improve the drug-like properties and curative efficacy of bioactive PSs by means of improving oral absorption, controlling the release, enhancing the in vivo retention ability, targeting the delivery, exerting synergistic effects, and so on. Specifically, nano-sized insoluble DDSs were mainly applied to improve the oral absorption and target delivery of PSs, among which liposome was especially suitable for immunoregulatory and/or anti-ischemic PSs due to its synergistic effects in immunoregulation and biomembrane repair. Chemical conjugation of PSs was mainly utilized to improve their oral absorption and/or prolong their blood residence. With formulation flexibility, in situ forming systems alone or in combination with drug conjugation could be used to achieve day(s)- or month(s)-long sustained delivery of PSs per dosing.     

Tumor microenvironment responsive drug delivery systems

Conventional tumor-targeted drug delivery systems (DDSs) face challenges, such as unsatisfied systemic circulation, low targeting efficiency, poor tumoral penetration, and uncontrolled drug release. Recently, tumor cellular molecules-triggered DDSs have aroused great interests in addressing such dilemmas. With the introduction of several additional functionalities, the properties of these smart DDSs including size, surface charge and ligand exposure can response to different tumor microenvironments for a more efficient tumor targeting, and eventually achieve desired drug release for an optimized therapeutic efficiency. This review highlights the recent research progresses on smart tumor environment responsive drug delivery systems for targeted drug delivery. Dynamic targeting strategies and functional moieties sensitive to a variety of tumor cellular stimuli, including pH, glutathione, adenosine-triphosphate, reactive oxygen species, enzyme and inflammatory factors are summarized. Special emphasis of this review is placed on their responsive mechanisms, drug loading models, drawbacks and merits. Several typical multi-stimuli responsive DDSs are listed. And the main challenges and potential future development are discussed.     

Ion-exchange resins: carrying drug delivery forward

Ion-exchange resins (IER), or ionic polymer networks, have received considerable attention from pharmaceutical scientists because of their versatile properties as drug-delivery vehicles. In the past few years, IER have been extensively studied in the development of novel drug-delivery systems (DDSs) and other biomedical applications. Some of the DDSs containing IER have been introduced into the market. In this review, the applications of IER in drug delivery research are discussed.     

Stimuli-responsive drug delivery systems for head and neck cancer therapy

Head and neck cancer (HNC) is among the most common malignancy that has a profound impact on human health and life quality. The treatment for HNC, especially for the advanced cancer is stage-dependent and in need of combined therapies. Various forms of adjuvant treatments such as chemotherapy, phototherapy, hyperthermia, gene therapy have been included in the HNC therapy. However, there are still restrictions with traditional administration such as limited in situ therapeutic effect, systemic toxicity, drug resistance, etc. In recent years, stimuli-responsive drug delivery systems (DDSs) have attracted the great attention in HNC therapy. These intelligent DDSs could respond to unique tumor microenvironment, external triggers or dual/multi stimulus with more specific drug delivery and release, leading to enhanced treatment efficiency and less reduced side effects. In this article, recent studies on stimuli-responsive DDSs for HNC therapy were summarized, which could respond to endogenous and exogenous triggers including pH, matrix metalloproteinases (MMPs), reactive oxygen species (ROS), redox condition, light, magnetic field and multi stimuli. Their therapeutic remarks, current limits and future prospect for these intelligent DDSs were discussed. Furthermore, multifunctional stimuli-responsive DDSs have also been reviewed. With the modification of drug carriers or co-loading with therapeutic agents. Those intelligent DDSs showed more biofunctions such as combined therapeutic effects or integration of diagnosis and treatment for HNC. It is believed that stimuli-responsive drug delivery systems showed great potential for future clinic translation and application for the treatment of HNC.     

Toxic and teratogenic silica nanowires in developing vertebrate embryos

Silica-based nanomaterials show promise for biomedical applications such as cell-selective drug delivery and bioimaging. They are easily functionalized, which allows for the conjugation or encapsulation of important biomolecules. Although recent in vitro studies suggested that silica-derived nanomaterials are nontoxic, in vivo studies of silica nanomaterial toxicity have not been performed. Using the embryonic zebrafish as a model system, we show that silica nanomaterials with aspect ratios greater than 1 are highly toxic (LD₅₀ = 110 pg/g embryo) and cause embryo deformities, whereas silica nanomaterials with an aspect ratio of 1 are neither toxic nor teratogenic at the same concentrations. Silica nanowires also interfere with neurulation and disrupt expression of sonic hedgehog, which encodes a key midline signaling factor. Our results demonstrate the need for further testing of nanomaterials before they can be used as platforms for drug delivery.From the Clinical EditorSilica-based nanomaterials show promise for biomedical applications such as cell-selective drug delivery and bioimaging. Using an embryonic zebrafish model system silica nanomaterials with aspect ratios greater than one were found to be highly toxic; whereas silica nanomaterials with an aspect ratio of one are neither toxic nor teratogenic. These results demonstrate the need for testing “nanomaterials" before they can be used as platforms for drug delivery.     

The advancing uses of nano-graphene in drug delivery

Introduction: Graphene has been received with great interest in various fields including biomedical applications. Due to its ultrahigh surface area and easy surface functionalization, single-layered graphene has been intensively explored for drug and gene delivery. Utilizing their intrinsic high near-infrared absorbance, graphene and its derivatives have been found to be excellent candidates for multimodal imaging guided combined cancer photothermal and chemo- and/or photodynamic therapies.

Areas covered: This review summarizes recent studies on the biomedical applications of various graphene-based nanomaterials. The authors provide a comprehensive summary on using properly functionalized nano-graphene and its derivatives for drug and gene delivery, as well as combination therapy of cancer.

Expert opinion: Regarding biomedical applications, the authors find that proper surface functionalization and controlled sizes of graphene-based nanomaterials are two crucial factors for efficient drug and gene delivery. Although a lot of work has demonstrated the successful delivery of anticancer drugs and genes using graphene-based nanomaterials as carriers, the correlations of their surface functionalization and size distribution and their therapeutic outcomes need more exploration. On the other hand, the long-term toxicological and metabolic behaviors of nano-graphene still merit significantly more effort before clinical use.     

Zinc-based metal–organic frameworks as nontoxic and biodegradable platforms for biomedical applications: review study

Abstract

Development of biomedical systems for controllable drug delivery systems and construction of biosensors is imperative to reduce side effects of common treatment techniques and enhance the therapeutic efficacy. To address this issue, metal–organic frameworks (MOFs) as hybrid porous polymeric structures have attracted worldwide attention due to their unprecedented opportunities in vast range of applications in diverse fields including chemistry, biological, and medicinal science as gas storage/separation, sensing, and drug delivery systems. Recently, biomedical application has become an interesting and promising issue for development and usage of multi-functional MOFs. Flexible chemical composition and versatile porous structure of MOFs enable the engineering and enhancement of their medical formulation and functionality as practical carriers for whether therapeutic or imaging agents. One important point in this domain is the efficient delivery of drugs in the body using nontoxic and biodegradable carriers. This review brings together the literatures that addressing the biomedical applications of Zinc-based MOFs (i.e. as drug delivery systems or nontoxic agent in matter of therapeutic applications) to present recent achievements in this interesting field.     

Recent advances in the role of supramolecular hydrogels in drug delivery

Introduction: Supramolecular hydrogels, formed by noncovalent crosslinking of polymeric chains in water, constitute an interesting class of materials that can be developed specifically for drug delivery and biomedical applications. The biocompatibility, stimuli responsiveness to various external factors, and powerful functionalization capacity of these polymeric networks make them attractive candidates for novel advanced dosage form design.

Areas covered: This review summarizes the significance of supramolecular hydrogels in various biomedical and drug delivery applications. The recent advancement of these hydrogels as potential advanced drug delivery systems (for gene, protein, anticancer and other drugs) is discussed. The importance of these hydrogels in biomedical applications, particularly in tissue engineering, biosensing, cell-culture research and wound treatment is briefly described.

Expert opinion: The use of supramolecular hydrogels in drug delivery is still in very early stages. However, the potential of such a system is undeniably important and very promising. A number of recent studies have been conducted, which mainly focus on the use of cyclodextrin-based host–guest complex as well as other supramolecular motifs to form supramolecular hydrogels for delivery of various classes of drugs, therapeutic agents, proteins and genes. However, there are still plenty of opportunities for further development in this area for drug delivery and other biomedical applications.     

Better safe than sorry: Understanding the toxicological properties of inorganic nanoparticles manufactured for biomedical applications

The development of nanoparticles for biomedical applications including medical imaging and drug delivery is currently undergoing a dramatic expansion. However, as the range of nanoparticle types and applications increases, it is also clear that the potential toxicities of these novel materials and the properties driving such toxic responses must also be understood. Indeed, a detailed assessment of the factors that influence the biocompatibility and/or toxicity of nanoparticles is crucial for the safe and sustainable development of the emerging nanotechnologies. This review summarizes some of the recent developments in the field of nanomedicine with particular emphasis on inorganic nanoparticles for drug delivery. The synthesis routes, physico-chemical characteristics, and cytotoxic properties of inorganic nanoparticles are thus explored and lessons learned from the toxicological investigation of three common types of engineered nanomaterials of titania, gold, and mesoporous silica are discussed. Emphasis is placed on the recognition versus non-recognition of engineered nanomaterials by the immune system, the primary surveillance system against microorganisms and particles, which, in turn, is intimately linked to the issue of targeted drug delivery using such nanomaterials as carrier systems.     

The alluring potential of functionalized carbon nanotubes in drug discovery

Importance of the field: The possibility of carbon nanotube integration into living systems for therapeutic and diagnostic purposes has opened the way to explore their applications in drug delivery and discovery. A wide variety of chemical approaches has been developed to functionalize carbon nanotubes with therapeutic molecules towards different biomedical uses. Areas covered in this review: This review covers the recent advances in the development of functionalized carbon nanotubes to offer improvements for different diseases, in particular for cancer therapy. What the reader will gain: Functionalized carbon nanotubes are able to transport therapeutic agents. Targeted methodologies using carbon nanotube-based conjugates have been investigated to improve the efficacy of some drugs. The capacity of such nanomaterials to seamlessly translocate into cells with alternative various mechanisms and their pharmacokinetic properties is also discussed. Take home message: Although at its infancy, functionalized carbon nanotubes are very promising as a new nanomedicine platform in the field of drug discovery and delivery. They have the capacity to cross biological barriers and can be eliminated via renal and/or fecal excretion. They can transport small drug molecules while maintaining - and in some cases improving - their therapeutic efficacy.