Role of nanotechnology in targeted drug delivery and imaging: a concise review

The use of nanotechnology in drug delivery and imaging in vivo is a rapidly expanding field. The emphases of this review are on biophysical attributes of the drug delivery and imaging platforms as well as the biological aspects that enable targeting of these platforms to injured and diseased tissues and cells. The principles of passive and active targeting of nanosized carriers to inflamed and cancerous tissues with increased vascular leakiness, overexpression of specific epitopes, and cellular uptake of these nanoscale systems are discussed. Preparation methods-properties of nanoscale systems including liposomes, micelles, emulsions, nanoparticulates, and dendrimer nanocomposites, and clinical indications are outlined separately for drug delivery and imaging in vivo. Taken together, these relatively new and exciting data indicate that the future of nanomedicine is very promising, and that additional preclinical and clinical studies in relevant animal models and disease states, as well as long-term toxicity studies, should be conducted beyond the "proof-of-concept" stage. Large-scale manufacturing and costs of nanomedicines are also important issues to be addressed during development for clinical indications.     

Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date

In this review we provide an up to date snapshot of nanomedicines either currently approved by the US FDA, or in the FDA clinical trials process. We define nanomedicines as therapeutic or imaging agents which comprise a nanoparticle in order to control the biodistribution, enhance the efficacy, or otherwise reduce toxicity of a drug or biologic. We identified 51 FDA-approved nanomedicines that met this definition and 77 products in clinical trials, with ~40% of trials listed in clinicaltrials.gov started in 2014 or 2015. While FDA approved materials are heavily weighted to polymeric, liposomal, and nanocrystal formulations, there is a trend towards the development of more complex materials comprising micelles, protein-based NPs, and also the emergence of a variety of inorganic and metallic particles in clinical trials. We then provide an overview of the different material categories represented in our search, highlighting nanomedicines that have either been recently approved, or are already in clinical trials. We conclude with some comments on future perspectives for nanomedicines, which we expect to include more actively-targeted materials, multi-functional materials (“theranostics”) and more complicated materials that blur the boundaries of traditional material categories. A key challenge for researchers, industry, and regulators is how to classify new materials and what additional testing (e.g. safety and toxicity) is required before products become available.     

Polysaccharide-based nucleic acid nanoformulations

Therapeutic application of nucleic acids requires their encapsulation in nanosized carriers that enable safe and efficient intracellular delivery. Before the desired site of action is reached, drug-loaded nanoparticles (nanomedicines) encounter numerous extra- and intracellular barriers. Judicious nanocarrier design is highly needed to stimulate nucleic acid delivery across these barriers and maximize the therapeutic benefit. Natural polysaccharides are widely used for biomedical and pharmaceutical applications due to their inherent biocompatibility. At present, there is a growing interest in applying these biopolymers for the development of nanomedicines. This review highlights various polysaccharides and their derivatives, currently employed in the design of nucleic acid nanocarriers. In particular, recent progress made in polysaccharide-assisted nucleic acid delivery is summarized and the specific benefits that polysaccharides might offer to improve the delivery process are critically discussed.     

European Commission-supported development of targeted nanomedicines: did MediTrans make a difference?

Nanotechnology-inspired approaches to particle design and formulation, an improved understanding of (patho) physiological processes and biological barriers to drug targeting, as well as the limited input of new chemical entities in the 'pipeline' of pharmaceutical companies, suggest a bright future for targeted nanomedicines as pharmaceuticals. There is an increased consensus to the view that a major limitation hampering the entry of targeted delivery systems into the clinic is that new concepts and innovative research ideas within academia are not being developed and exploited in close collaboration with the pharmaceutical industry. Thus, an integrated 'bench-to-clinic' approach realized within a structural collaboration between industry and academia, will facilitate and promote the progression of targeted nanomedicines towards clinical application. The MediTrans project performed under the EU Framework Program 6, was designed to contribute to this ambition. The objectives of this collaborative initiative were: to apply nanotechnology for development of innovative targeted drug-delivery systems; to optimize targeted nanomedicines by using imaging guidance; to promote structural collaboration between industry and academia; and to forward targeted nanomedicines towards the clinic and the market. In this article, we will briefly address the research content, outcome and impact of the MediTrans project.     

Nanomedicines and Nanodiagnostics Come of Age

Although the employment of biomedical colloids is not new, modern biomedical colloids, termed nanomedicines and nanodiagnostics, have enhanced functionality, in that the drug compound/diagnostic probe entrapped within the nanoparticle takes on the properties of the encapsulating nanoparticle. The nanoparticle's properties are specifically dictated by its size, shape, and surface chemistry; the net result in the case of medicines is an alteration of the drug's intrinsic pharmacokinetics and eventual drug targeting to the areas of pathology. The first nanomedicines, which really altered the pharmacokinetics of a drug molecule, were licensed in the early-to-mid 1990s. Since this time, these pioneering nanomedicines: liposomal doxorubicin (Doxil) and liposomal amphotericin B (Ambisome), have been followed by medicines such as albumin-stabilised paclitaxel (Abraxane) and biomedical sentinel lymph node nanodiagnostics such as Sienna+. The clinical trials database is heavily populated with nanosystem trials—an indication that these agents are growing in stature and will be utilised in an expanding list of clinical situations. Although the intravenous route is the route of choice for the current nanoparticles, new administration routes such as the pulmonary route are already in clinical testing, and researchers are working on the preclinical development of oral nanomedicines.     

Nanoparticle therapeutics for prostate cancer treatment

The application of nanotechnology in medicine is offering many exciting possibilities in healthcare. Engineered nanoparticles have the potential to revolutionize the diagnosis and the therapy of several diseases, particularly by targeted delivery of anticancer drugs and imaging contrast agents. Prostate cancer, the second most common cancer in men, represents one of the major epidemiological problems, especially for patients in the advanced age. There is a substantial interest in developing therapeutic options for treatment of prostate cancer based on use of nanodevices, to overcome the lack of specificity of conventional chemotherapeutic agents as well as for the early detection of precancerous and malignant lesions. Herein, we highlight on the recent development of nanotechnology strategies adopted for the management of prostate cancer. In particular, the combination of targeted and controlled-release polymer nanotechnologies has recently resulted in the clinical development of BIND-014, a promising targeted Docetaxel-loaded nanoprototype, which can be validated for use in the prostate cancer therapy. However, several limitations facing nanoparticle delivery to solid tumours, such as heterogeneity of intratumoural barriers and vasculature, cytotoxicity and/or hypersensitivity reactions to currently available cancer nanomedicines, and the difficult in developing targeted nanoparticles with optimal biophysicochemical properties, should be still addressed for a successful tumour eradication.     

Challenges in Development of Nanoparticle-Based Therapeutics

In recent years, nanotechnology has been increasingly applied to the area of drug development. Nanoparticle-based therapeutics can confer the ability to overcome biological barriers, effectively deliver hydrophobic drugs and biologics, and preferentially target sites of disease. However, despite these potential advantages, only a relatively small number of nanoparticle-based medicines have been approved for clinical use, with numerous challenges and hurdles at different stages of development. The complexity of nanoparticles as multi-component three dimensional constructs requires careful design and engineering, detailed orthogonal analysis methods, and reproducible scale-up and manufacturing process to achieve a consistent product with the intended physicochemical characteristics, biological behaviors, and pharmacological profiles. The safety and efficacy of nanomedicines can be influenced by minor variations in multiple parameters and need to be carefully examined in preclinical and clinical studies, particularly in context of the biodistribution, targeting to intended sites, and potential immune toxicities. Overall, nanomedicines may present additional development and regulatory considerations compared with conventional medicines, and while there is generally a lack of regulatory standards in the examination of nanoparticle-based medicines as a unique category of therapeutic agents, efforts are being made in this direction. This review summarizes challenges likely to be encountered during the development and approval of nanoparticle-based therapeutics, and discusses potential strategies for drug developers and regulatory agencies to accelerate the growth of this important field.     

PEGylated nanomedicines: recent progress and remaining concerns

Introduction: Recent biopharma deals related to nanocarrier drug delivery technologies highlight the emergence of nanomedicine. This is perhaps an expected culmination of many years of research demonstrating the potential of nanomedicine as the next generation of therapeutics with improved performance. PEGylated nanocarriers play a key role within this field.

Areas covered: The drug delivery advantages of nanomedicines in general are discussed, focusing on nanocarriers and PEGylated nanomedicines, including products under current development/clinical evaluation. Well-established drug delivery benefits of PEGylation (e.g., prolonged circulation) are only briefly covered. Instead, attention is deliberately made to less commonly reported advantages of PEGylation, including mucosal delivery of nanomedicines. Finally, some of the issues related to the safety of PEGylated nanomedicines in clinical application are discussed.

Expert opinion: The advent of nanomedicine providing therapeutic options of refined performance continues. Although PEGylation as a tool to improve the pharmacokinetics of nanomedicines is well established and is used clinically, other benefits of ‘PEGnology', including enhancement of physicochemical properties and/or biocompatibility of actives and/or drug carriers, as well as mucosal delivery, have attracted less attention. While concerns regarding the clinical use of PEGylated nanomedicines remain, evidence suggests that at least some safety issues may be controlled by adequate designs of nanosystems.     

The design of clinical trials for new molecularly targeted compounds: progress and new initiatives

Investigators involved in the development of cancer therapeutics are testing new trial designs and endpoints in order to accommodate the perceived challenges in defining appropriate doses and schedules for further testing. Many new agents with specific molecular targets have entered clinical development or are being considered for development. While some of the agents have both toxicity and antitumour efficacy apparent at clinically achievable doses, thus the use of traditional algorithms is appropriate, others have significant clinical activity at doses considerably lower than the maximum tolerated dose. New initiatives in clinical trial design, both phase I and phase II may allow the development of appropriate plans for the development of these new molecularly targeted agents. Measures of target effect (tissue or imaging) are now commonly included in early trials of new targeted compounds, in an attempt to demonstrate proof of principle as well as guide dose selection. Phase II trial designs including novel correlative, imaging and clinical endpoints are being tested. Alternate endpoints such as progression or time to progression are being increasingly considered, and novel designs such as randomized discontinuation designs, multinomial designs and growth modulation indices are being prospectively tested. Progress in this area of early trial design are reviewed.     

Nanomedicine-based drug targeting for psoriasis: potentials and emerging trends in nanoscale pharmacotherapy

Introduction: Psoriasis is a T-cell mediated autoimmune inflammatory skin disease recognized by skin surface inflammation, epidermal proliferation, hyperkeratosis, angiogenesis and anomalous keratinization. Currently, various pharmacotherapies are available for it; however, pharmacotherapy based on conventional formulations can provide therapeutic benefits only to a limited extent. Recent advancement in nanotechnology-based nanomedicines has led to the possibility of improving the efficacy and safety of pharmacotherapeutic agents for psoriasis.

Areas covered: This review covers the brief pathophysiology of psoriasis, available medications and its associated challenges in treatment. Collective accounts of various drugs acting on different molecular targets of psoriasis and the role of nanomedicines in their effective targeting are discussed. Moreover, newer approaches in psoriatic therapy such as combination drug targeting and physical techniques of topical permeation enhancement along with nanomedicines are also discussed.

Expert opinion: Novel nanomedicines (such as liposomes, polymeric nanoparticles, etc.) have shown their potential in improving therapeutic benefits of antipsoriatic drugs by increasing their therapeutic efficacy with minimal toxicity. Nevertheless, while the results on animal models using nanomedicine-based drug targeting of psoriasis via different route seem promising, lack of sufficient evidence in a clinical setup is a constraint and more clinical studies on the efficacy and safety of nanomedicines in psoriasis therapy are required.     

Summary Report of PQRI Workshop on Nanomaterial in Drug Products: Current Experience and Management of Potential Risks

At the Product Quality Research Institute (PQRI) Workshop held last January 14–15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for in vitro characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced in vivo and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials.KEY WORDS: nanomaterials, nanomedicine, nanotechnology, PQRI, risk management, USFDA     

Nanomaterials for (Nano)medicine

Next generation nanomedicine will rely on innovative nanomaterials capable of unprecedented performance. Which ones are the most promising candidates for a medicinal chemist?The expectations are high for the next generation of nanomedicines: a personalized and efficient therapy with lower side effects. In tissue engineering, nanomaterial-based scaffolds will offer a biodegradable support for cell growth and infiltration to be naturally replaced with time by new biological tissue. In drug delivery, smart nanodevices will target the disease site; there, an external trigger will prompt the controlled release of multiple agents for sensing, high-resolution imaging, and therapy. How can we conceive such a level of advanced performance without using innovative components? What are the nanomaterials of the future, and which ones are the most appealing for a medicinal chemist?The nanomaterial landscape is vast (Figure ​(Figure1).1). The medicinal chemist that looks close-by for familiar chemistry will see all of the well-characterized polymers, lipids, peptides and proteins, sugars, and surfactants that can be engineered into novel nanoformulations. Liposomes, dendrimers, and nanogels have been used for both controlled drug delivery and cell growth scaffolds. They are present in many nanomedicines that made it to the clinic, and most likely, they will appear to some extent also in the nanomedicines of the future.¹ However, if we look a bit further and stretch our eyes toward the horizon, we will see how the landscape changes as we encounter the less-explored nanomaterials. Nanoparticles (NPs), quantum dots (QDs), and carbon nanotubes (CNTs), in one form or another, are all there. Which way does a medicinal chemist have to go for the best ingredients for the next generation nanomedicines?Open in a separate windowFigure 1The medicinal chemist looks at the vast landscape of nanomaterials.Many chemists would make their bet on mesoporous silica NPs. These are among the best-characterized NPs in vivo and indeed offer a number of advantages. Their synthesis can be fine-tuned to a variety of shapes and sizes (down to a few nanometers). The use of silane mixtures in their preparation allows for convenient incorporation of functional groups of choice (e.g., amino, carboxylic, thiol, etc.) for incorporation of therapeutic or imaging agents. Their porosity allows for high drug loading (up to 35 wt %).² Remarkably, the “Cornell dots” are the first silica-based multimodal (optical/PET) diagnostic NPs recently approved for human clinical trials; their PEG coating and small size (<10 nm) allow for good biodistribution in a melanoma model, and fluorescent dye encapsulation in the NP core gives them notable brightness.^3,4 However, despite these very encouraging advances, concerns still exist on the nanomaterial landscape about the coating stability of mesoporous silica NPs, since it has been shown that uncoated silica NPs are hemolytic.⁵Magnetic NPs offer different advantages. They are well-known in medicine as MRI agents; in addition, their ability to respond to external magnetic fields gives an opportunity to develop cutting edge applications in protein and cell manipulation.⁶ In particular, superparamagnetic iron oxide NPs (SPIONs) have attracted a lot of attention for drug delivery applications in theranostics (i.e., combined therapy and diagnosis). One of the promises of SPIONs is targeted delivery to the disease site following an external magnetic force. In fact, their directional movement is usually hampered by blood flow, and their sensitivity to magnets can be notably reduced by the presence of a polymer coating (e.g., dextran). However, this organic “shell” is essential to reduce NPs undesired interaction with proteins and their subsequent opsonization. Therefore, SPIONs design needs careful fine-tuning of the “shell” for optimal performance. To date, opportunities exist to improve SPIONs colloidal stability in biological fluids (i.e., loss of the polymer coating) and to control drug delivery, avoiding undesired burst release from the polymer component.⁷Another class that is drawing a lot of attention is gold NPs (AuNPs). Besides spherical NPs, the literature is rich with nanorods, nanocages, nanostars, and gold shells used to coat other NPs (e.g., SPION cores). Gold has been known in medicine for a very long time, but the attentive reader will note that the behavior of nanosized gold objects is a different matter, due to the high surface area and unique physicochemical properties. The shape of AuNPs has a big impact on their properties: spheres absorb visible light, and rods, cages, and shells absorb light in the near-infrared (NIR) region, where the human body is mostly transparent. NIR absorption is very useful, since it is employed in photothermal therapy (i.e., for heat generation to damage diseased tissue) and in high-resolution photoacustic imaging (i.e., for the generation of ultrasound waves). AuNPs, modified with both a strong Raman scatterer and an antibody, enhance the Raman response (surface enhanced Raman scattering, SERS), whereas the antibody imparts antigenic specificity.⁸There is an increasing number of studies on the matter, but the heterogeneity of gold NP formulations makes it difficult to generalize important aspects such as biosafety assessments.⁹ In addition, despite the vast number of studies on gold nanomaterials, the functionalization chemistry of gold NPs usually revolves around the use of either thiols or amines, somewhat limiting the choice of triggers for drug loading and release. Nevertheless, imaginative variations have been found, such as the photothermal release of DNA cargos upon laser irradiation.¹⁰QDs are yet another class of which we hear more and more in nanomedicine, especially in applications of multimodal imaging. The battle against cancer needs weapons of increasing sophistication, including tools to locate micrometastasis with exquisite spatiotemporal resolution. To this end, we may rely on multimodal imaging, because it is only with the combination of different techniques that we can go beyond the limitations of each modality, especially for imaging of deep tissues.¹¹ QDs could be useful components of sophisticated nanodevices due to their very small size (typically of only a few nanometers), remarkable brightness, photostability, and ample offering of emission light colors for optical detection. Nevertheless, major limitations are posed by their chemical nature, since they are typically composed of heavy metals (e.g., cadmium, lead), for which QDs stability and safe excretion from the human body is a must.¹²In the field of theranostics, CNTs are excellent candidates, as they exhibit many properties relevant to these objectives. For instance, CNTs possess relatively strong NIR absorption, which can be used for both high-resolution imaging (e.g., photoacustic modality) and photothermal therapy.¹¹ Although biocompatibility and safety of CNTs are still an open issue, it is important to note that CNTs comprise a highly heterogeneous class of materials, for which biocompatibility data cannot, and should not, be generalized. There is a growing body of work that shows that CNT fate in vivo is highly dependent on their purity, physical properties (i.e., length, diameter, etc.), and chemical nature (i.e., functionalization). Importantly, there is increasing evidence that biodegradation of CNTs can be achieved by appropriate chemical modification.¹³ Derivatization of CNTs offers a variety of options for the imaginative medicinal chemist, who can covalently attach the polymer of choice for favorable interactions with biological entities. In addition to their high external surface, their hollow nature might permit loading with drugs or other bioactive cargoes, for their safe delivery in a cellular environment bypassing biological barriers otherwise encountered by other vectors.¹⁴ For instance, data exist on the ability of certain tubes to act as “cell membrane needles” and avoid the endocytic pathway.^15,16 Another unique property is their ability to boost electrical activity of multilayered neuronal networks and cultured cardiac myocytes: the mechanisms of this phenomenon are still unclear and obviously deserve further investigation.^17,18 Clearly, mastering such properties would pave the way to innovative tissue engineering that, until a few years back, was simply unthinkable. In our point of view, their unique properties offer ample opportunity for unprecedented performance in the field of “smart” nanomedicines; however, their application in the field is still in its infancy.¹⁹In conclusion, the landscape of nanomaterials for medicines of the next generation is rich with options, and innovative solutions will likely be found in the wise combination of different components. It is clear that the examples reported in this viewpoint are only a few, representative of a class of materials that is continuously expanding and that includes an exceedingly high number of examples and ideas. The medicinal chemists who venture into this field should not impose limits on their imagination; instead, they should reach out to and partner with physicists, biologists, and clinicians to find creative solutions to these complex, multidisciplinary problems. We believe that hybrid, multifunctional nanomaterials will be the key components of the next generation of nanomedicines, and the brave medicinal chemists shall venture into the field to make them a reality.     

Recent progress in dendrimer-based nanomedicine development

Dendrimers offer well-defined nanoarchitectures with spherical shape, high degree of molecular uniformity, and multiple surface functionalities. Such unique structural properties of dendrimers have created many applications for drug and gene delivery, nanomedicine, diagnostics, and biomedical engineering. Dendrimers are not only capable of delivering drugs or diagnostic agents to desired sites by encapsulating or conjugating them to the periphery, but also have therapeutic efficacy in their own. When compared to traditional polymers for drug delivery, dendrimers have distinct advantages, such as high drug-loading capacity at the surface terminal for conjugation or interior space for encapsulation, size control with well-defined numbers of peripheries, and multivalency for conjugation to drugs, targeting moieties, molecular sensors, and biopolymers. This review focuses on recent applications of dendrimers for the development of dendrimer-based nanomedicines for cancer, inflammation, and viral infection. Although dendrimer-based nanomedicines still face some challenges including scale-up production and well-characterization, several dendrimer-based drug candidates are expected to enter clinical development phase in the near future.     

Endocytosis and intracellular trafficking as gateways for nanomedicine delivery: opportunities and challenges

More than 40 nanomedicines are already in routine clinical use with a growing number following in preclinical and clinical development. The therapeutic objectives are often enhanced disease-specific targeting (with simultaneously reduced access to sites of toxicity) and, especially in the case of macromolecular biotech drugs, improving access to intracellular pharmacological target receptors. Successful navigation of the endocytic pathways is usually a prerequisite to achieve these goals. Thus a comprehensive understanding of endocytosis and intracellular trafficking pathways in both the target and bystander normal cell type(s) is essential to enable optimal nanomedicine design. It is becoming evident that endocytic pathways can become disregulated in disease and this, together with the potential changes induced during exposure to the nanocarrier itself, has the potential to significantly impact nanomedicine performance in terms of safety and efficacy. Here we overview the endomembrane trafficking pathways, discuss the methods used to determine and quantitate the intracellular fate of nanomedicines, and review the current status of lysosomotropic and endosomotropic delivery. Based on the lessons learned during more than 3 decades of clinical development, the need to use endocytosis-relevant clinical biomarkers to better select those patients most likely to benefit from nanomedicine therapy is also discussed.     

磁共振成像可视化栓塞微球研究进展

微球是临床介入栓塞治疗最常用的材料,但目前绝大多数栓塞微球在临床常用的影像设备下是不可视的,即不能被计算机断层扫描(computed tomography,CT)或磁共振成像(magnetic resonance ima-ging,MRI)设备观察到,导致微球所在的位置及其分布不能被及时和准确地监测到.近年来,为提高栓...     

Copolymers of poly(lactic acid) and d-α-tocopheryl polyethylene glycol 1000 succinate-based nanomedicines: versatile multifunctional platforms for cancer diagnosis and therapy

Introduction: The major drawbacks associated with most of the anti-cancer drugs are their potential adverse effects. Distribution of these drugs throughout the body causes untoward adverse effects and less accumulation of drug at the site of tumors also causes decrease in therapeutic efficacy. Targeted nanomedicines are the emerging systems to improve the targetability of drug to the tumor site and to reduce the toxicity with maximum efficacy. Copolymers of poly-lactic acid (PLA) and d-α-tocopheryl polyethylene glycol 1000 succinate (Vitamin-E TPGS or TPGS) are innovative materials being actively investigated for the fabrication of non-targeted and targeted nanomedicines for diagnosis and therapy of cancer.

Areas covered: In this review, different nanomedicines of copolymers such as poly-lactic acid – polyoxyethylene sorbitan monooleate (PLA – Tween® 80), poly-lactic acid – poly-ethyleneglycol (PLA-PEG), poly-lactic acid-d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS) and TPGS-based nanomedicines (i.e., TPGS emulsified polymeric nanoparticles, TPGS prodrugs, TPGS liposomes, and TPGS micelles) for the diagnosis and therapy of cancer have been discussed.

Expert opinion: PLA, PLA-Tween® 80, PLA-PEG, PLA-TPGS, and TPGS are the promising polymeric biomaterials well studied as cancer nanomedicines. These biomaterials have proved that they could be applied in the fabrication of multifunctional nanomedicines for the future needs in simultaneous diagnosis of cancer as well as targeted chemotherapy.     

Liposomes and their applications in molecular imaging

Molecular imaging is a relatively new discipline with a crucial role in diagnosis and treatment tracing of diseases through characterization and quantification of biological processes at cellular and sub-cellular levels of living organisms. These molecular targeted systems can be conjugated with contrast agents or radioligands to obtain specific molecular probes for the purpose of diagnosis of diseases more accurately by different imaging modalities. Nowadays, an interesting new approach to molecular imaging is the use of stealth nanosized drug delivery systems such as liposomes having convenient properties such as biodegradability, biocompatibility and non-toxicity and they can specifically be targeted to desired disease tissues by combining with specific targeting ligands and probes. The targeted liposomes as molecular probes in molecular imaging have been evaluated in this review. Therefore, the essential point is detection of molecular target of the disease which is different from normal conditions such as increase or decrease of a receptor, transporter, hormone, enzyme etc, or formation of a novel target. Transport of the diagnostic probe specifically to targeted cellular, sub-cellular or even to molecular entities can be performed by molecular imaging probes. This may lead to produce personalized medicine for imaging and/or therapy of diseases at earlier stages.     

The Growing Field of Nanomedicine and Its Relevance to Pharmacy Curricula

The field of nanomedicine is a rapidly growing scientific domain. Nanomedicine encompasses a diverse number of active pharmaceutical ingredients. Submissions of Investigational New Drugs and New Drug Applications have risen dramatically over the last decade. There are over 50 nanomedicines approved for use by the US Food and Drug Administration (FDA). Because of the fundamental role pharmacists will play in therapeutic and administrative decisions regarding nanomedicines, it is imperative for future pharmacists to gain exposure early in their training to this rapidly evolving class of drugs. This commentary describes nanomedicines, discusses current regulatory challenges, and provides recommendations for judicious incorporation of nanomedicine topics into the Doctor of Pharmacy curriculum based on emerging pharmaceutical and clinical science applications.     

Liposomes and their applications in molecular imaging

Molecular imaging is a relatively new discipline with a crucial role in diagnosis and treatment tracing of diseases through characterization and quantification of biological processes at cellular and sub-cellular levels of living organisms. These molecular targeted systems can be conjugated with contrast agents or radioligands to obtain specific molecular probes for the purpose of diagnosis of diseases more accurately by different imaging modalities. Nowadays, an interesting new approach to molecular imaging is the use of stealth nanosized drug delivery systems such as liposomes having convenient properties such as biodegradability, biocompatibility and non-toxicity and they can specifically be targeted to desired disease tissues by combining with specific targeting ligands and probes. The targeted liposomes as molecular probes in molecular imaging have been evaluated in this review. Therefore, the essential point is detection of molecular target of the disease which is different from normal conditions such as increase or decrease of a receptor, transporter, hormone, enzyme etc, or formation of a novel target. Transport of the diagnostic probe specifically to targeted cellular, sub-cellular or even to molecular entities can be performed by molecular imaging probes. This may lead to produce personalized medicine for imaging and/or therapy of diseases at earlier stages.     

Efficacy and safety of poly (gamma-glutamic acid) based nanoparticles (gamma-PGA NPs) as vaccine carrier

Recently, nanoscopic systems that incorporate therapeutic agents, and molecular targeting and diagnostic imaging capabilities are emerging as the next generation of functional nanomedicines to improve the outcome of drug therapeutics. Among the many nanoparticulate systems, micelle-like aggregates or nanoparticles formed with amphiphilic block- or graft- copolymers are currently being studied for possible application as protein carriers. We recently developed a technique to prepare uniform nanoparticles (gamma-PGA NPs) using amphiphilic gamma-PGA (gamma-PGA-L-PAE), in which L-phenylalanine ethyl ester (L-PAE) is introduced as a hydrophobic residue into the alpha-position group carboxyl of poly(gamma-glutamic acid) (gamma-PGA) which is a biodegradable polymer derived from a natto mucilage. gamma-PGA NPs are excellent vaccine carriers capable of delivering antigenic proteins to antigen-presenting cells (APCs) and eliciting potent immune responses based on antigen-specific cytotoxic T lymphocytes. In mice, subcutaneous immunization with gamma-PGA NPs entrapping ovalbumin (OVA) more effectively inhibited the growth of OVA-transfected tumors than immunization with OVA emulsified using Freund's complete adjuvant. In addition, gamma-PGA NPs did not induce histopathologic changes after subcutaneous injection or acute toxicity through intravenous injection. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins into APCs through cytosolic translocation from the endosomes, which is a key process of gamma-PGA NP-mediated anti-tumor immune responses. These antigen-capturing APCs migrated to regional lymph nodes. Our results demonstrate that a gamma-PGA NP system for antigen delivery will advance the clinical utility of vaccines against cancer.