Review on design strategies and considerations of polysaccharide-based smart drug delivery systems for cancer therapy.

The unique natural advantages of polysaccharide materials have attracted attention in biomedical applications. The abundant modifiable functional groups on the polysaccharide materials surface can facilitate the synthesis of various multifunctional drug delivery carriers. Especially in tumor therapy, the designs of polysaccharide-based drug delivery carriers are diverse. Therefore, this review summarized several latest types of polysaccharide-based drug carriers designs, and focused on the latest design strategies and considerations of drug carriers with polysaccharides as the main structure. It is expected to provide some design ideas and inspiration for subsequent polysaccharide-based drug delivery systems.

Nanotechnology for Topical Drug Delivery to the Anterior Segment of the Eye.

Topical drug delivery is one of the most challenging aspects of eye therapy. Eye drops are the most prevalent drug form, especially for widely distributed anterior segment eye diseases (cataracts, glaucoma, dry eye syndrome, inflammatory diseases, etc.), because they are convenient and easy to apply by patients. However, conventional drug formulations are usually characterized by short retention time in the tear film, insufficient contact with epithelium, fast elimination, and difficulties in overcoming ocular tissue barriers. Not more than 5% of the total drug dose administered in eye drops reaches the interior ocular tissues. To overcome the ocular drug delivery barriers and improve drug bioavailability, various conventional and novel drug delivery systems have been developed. Among these, nanosize carriers are the most attractive. The review is focused on the different drug carriers, such as synthetic and natural polymers, as well as inorganic carriers, with special attention to nanoparticles and nanomicelles. Studies in vitro and in vivo have demonstrated that new formulations could help to improve the bioavailability of the drugs, provide sustained drug release, enhance and prolong their therapeutic action. Promising results were obtained with drug-loaded nanoparticles included in in situ gel.

Cyclic Cell-Penetrating Peptides as Efficient Intracellular Drug Delivery Tools.

Cyclic cell-penetrating peptides are relatively a newer class of peptides that have a huge potential for the intracellular delivery of therapeutic agents aimed at treating challenging ailments like multidrug-resistant bacterial diseases, cancer, and HIV infection. Cell-penetrating peptides (CPPs) have been extensively explored as intracellular delivery vehicles; however, they have some inherent limitations like poor stability, endosomal entrapment, toxicity, and suboptimal cell penetration. Owing to their favorable properties that avoid these limitations, cyclic CPPs can provide a good alternative to linear CPPs. Several Reviews have been published in the past decade that cover CPPs and cyclic peptides independently. To the best of our knowledge, this is one of the first Reviews that covers cyclic CPPs comprehensively in the light of studies published so far. In this Review, we have detailed examples of cyclic CPPs, their structures, and cyclization strategies followed by a detailed account of their advantages over their linear counterparts. A hot area in cyclic CPPs is the exploration of cell-penetration mechanisms; this Review highlights this topic in detail. Finally, we will review the applications of cyclic CPPs, followed by conclusions and future prospects.

Nanotechnology Advanced Strategies for the Management of Diabetes Mellitus.

BACKGROUND: Medications currently available for the management of diabetes mellitus are inconvenient and have some limitations. Thus, investigations for novel approaches are needed to deliver and target antidiabetics safely to the site of action. OBJECTIVE: The present review emphasizes the limitations of conventional antidiabetics and provides the recent progresses of nanotechnology in the treatment of diabetes mellitus with a special highlight on the novel nanocarriers methodologies employed as antidiabetic drug delivery systems. METHOD: The potential nanocarriers employed for the treatment of diabetes comprise liposomes, niosomes, self-nanoemulsifying drug delivery systems, polymeric nanoparticles, gold nanoparticles, dendrimers and micelles. Herbal nanomedicine has also emerged to be a promising way for adequate delivery of herbal compounds. Other nanotechnology approaches involve the usage of oral insulin, inhalable insulin, artificial pancreas, and nanopump. RESULTS: Nanocarriers have proved to lead a successful delivery of antidiabetic medications, aiming at drug targeting for enhanced efficacy and safety. CONCLUSION: These innovative generations of drug delivery systems have important benefits over conventionally existing ones. The future of nanotechnology in the management of diabetes is still open with several prospects and will be of pronounced significance.

Nano Drug Delivery in Treatment of Oral Cancer, A Review of the Literature.

Oral Cancer (OC) is a serious and growing problem which constitutes a huge burden on people in more and less economically developed countries alike. The scenario is clearly depicted from the increase in the expected number of new cases in the US diagnosed with OC from 49,670 people in 2016, to 49,750 cases in 2017. The situation is even more alarming in India, with 75,000 to 80,000 new cases being reported every year, thus making it the OC capital of the world. Leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis, discoid lupus erythmatosus, hereditary disorders such as dyskeratosis congenital and epidermolisys bullosa are highlighted by WHO expert working group as the predisposing factors increasing the risk of OC. Consumption of tobacco and alcohol, genetic factors, and human papilloma virus are assigned as the factors contributing to the aetiology of OC. On the other hand, pathogenesis of OC involves not only apoptosis but also pain, inflammation and oxidative stress. Inspite of current treatment options (surgery, radiotherapy, and chemotherapy), OC is often associated with recurrence and formation of secondary primary tumours resulting in poor overall survival rates (∼50%). The intervention of nano technology-based drug delivery systems as therapeutics for cancers is often viewed as a cutting edge for technologists. Though ample literature on the usefulness of nano-coutured cancer therapeutics, rarely any product is in pipeline. Yet, despite all the hype about nanotechnology, there are few ongoing trials. This review discusses the current and future trends of nano-based drug delivery for the treatment of OC.

Current Strategies for Brain Drug Delivery.

The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.

Smart materials on the way to theranostic nanorobots: Molecular machines and nanomotors, advanced biosensors, and intelligent vehicles for drug delivery.

BACKGROUND: Theranostics, a fusion of two key parts of modern medicine - diagnostics and therapy of the organism's disorders, promises to bring the efficacy of medical treatment to a fundamentally new level and to become the basis of personalized medicine. Extrapolating today's progress in the field of smart materials to the long-run prospect, we can imagine future intelligent agents capable of performing complex analysis of different physiological factors inside the living organism and implementing a built-in program thereby triggering a series of therapeutic actions. These agents, by analogy with their macroscopic counterparts, can be called nanorobots. It is quite obscure what these devices are going to look like but they will be more or less based on today's achievements in nanobiotechnology. SCOPE OF REVIEW: The present Review is an attempt to systematize highly diverse nanomaterials, which may potentially serve as modules for theranostic nanorobotics, e.g., nanomotors, sensing units, and payload carriers. MAJOR CONCLUSIONS: Biocomputing-based sensing, externally actuated or chemically "fueled" autonomous movement, swarm inter-agent communication behavior are just a few inspiring examples that nanobiotechnology can offer today for construction of truly intelligent drug delivery systems. GENERAL SIGNIFICANCE: The progress of smart nanomaterials toward fully autonomous drug delivery nanorobots is an exciting prospect for disease treatment. Synergistic combination of the available approaches and their further development may produce intelligent drugs of unmatched functionality.

Classes and prediction of cell-penetrating peptides.

The classical view on how peptides enter cells has been changed due to the development in the research field of cell-penetrating peptides (CPPs). During the last 15 years, more than 100 peptide sequences have been published to enter cells and also to bring different biological cargoes with them. Here, we present an overview of CPPs, mainly trying to analyze their common properties yielding the prediction of their cell-penetrating properties. Furthermore, examples of recent research, ideas on classification and uptake mechanisms, as well as a summary of the therapeutic potential of CPPs are presented.

Polymeric micelles as a new drug carrier system and their required considerations for clinical trials.

IMPORTANCE OF THE FIELD: A polymeric micelle is a macromolecular assembly composed of an inner core and an outer shell, and most typically is formed from block copolymers. In the last two decades, polymeric micelles have been actively studied as a new type of drug carrier system, in particular for drug targeting of anticancer drugs to solid tumors. AREAS COVERED IN THIS REVIEW: In this review, polymeric micelle drug carrier systems are discussed with a focus on toxicities of the polymeric micelle carrier systems and on pharmacological activities of the block copolymers. In the first section, the importance of the above-mentioned evaluation of these properties is explained, as this importance does not seem to be well recognized compared with the importance of targeting and enhanced pharmacological activity of drugs, particularly in the basic studies. Then, designs, types and classifications of the polymeric micelle system are briefly summarized and explained, followed by a detailed discussion regarding several examples of polymeric micelle carrier systems. WHAT THE READER WILL GAIN: Readers will gain a strategy of drug delivery with polymeric carriers as well as recent progress of the polymeric micelle carrier systems in their basic studies and clinical trials. TAKE HOME MESSAGE: The purpose of this review is to achieve tight connections between the basic studies and clinical trials.

[Thermosensitive polymers in drug form technology. I. Classification and characteristics]. / Termowrazliwe polimery w technologii postaci leku. I. Klasyfikacja i charakterystyka.

The following presentation is a review of literature related to application of thermosensitive polymers in technology of drug form. In this review described the classsification and examples of this polymers. Thermosensitive drug delivery can be used as substances carriers, which are applied in oral system, vaginal systems of release, applied on skin, the rectal, nasal, passed to eyes and parenteral. Sol-gel transition of the prepared formulations at physiological temperature ranges of the body makes possible their application in the liquid state and subsequent gelification in situ providing a prolonged release of the active substance at the application site.

[Thermosensitive polymers in drug form technology. II. Possibilities of use of thermosensitive polymers as active substance carriers]. / Termowrazliwe polimery w technologii postaci leku. II. Mozliwosci zastosowania polimerów termowrazliwych jako nosników substancji leczniczej.

Thermosensitive drug delivery can be used as substances carriers, which are applied in oral system, vaginal systems of release, applied on skin, the rectal, nasal, passed to eyes and parenteral. Sol-gel transition of the prepared formulations at physiological temperature ranges of the body makes possible their application in the liquid state and subsequent gelification in situ providing a prolonged release of the active substance at the application site.

Biodegradable nanoparticles for cytosolic delivery of therapeutics.

Many therapeutics require efficient cytosolic delivery either because the receptors for those drugs are located in the cytosol or their site of action is an intracellular organelle that requires transport through the cytosolic compartment. To achieve efficient cytosolic delivery of therapeutics, different nanomaterials have been developed that consider the diverse physicochemical nature of therapeutics (macromolecule to small molecule; water soluble to water insoluble) and various membrane associated and intracellular barriers that these systems need to overcome to efficiently deliver and retain therapeutics in the cytoplasmic compartment. Our interest is in investigating PLGA and PLA-based nanoparticles for intracellular delivery of drugs and genes. The present review discusses the various aspects of our studies and emphasizes the need for understanding of the molecular mechanisms of intracellular trafficking of nanoparticles in order to develop an efficient cytosolic delivery system.

Polymer carriers for drug delivery in tissue engineering.

Growing demand for tissues and organs for transplantation and the inability to meet this need using by autogeneic (from the host) or allogeneic (from the same species) sources has led to the rapid development of tissue engineering as an alternative. Tissue engineering aims to replace or facilitate the regrowth of damaged or diseased tissue by applying a combination of biomaterials, cells and bioactive molecules. This review focuses on synthetic polymers that have been used for tissue growth scaffold fabrication and their applications in both cell and extracellular matrix support and controlling the release of cell growth and differentiation supporting drugs.

A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes.

Amphiphilic block copolymers are able to form a range of different nanoparticulate structures. These include micelles, nanospheres, nanocapsules, and polymersomes. This review attempts to clarify some of the terminology used in the literature by providing an overview of the major features of each type of nanoparticle and the factors that influence the formation of particular nanoparticulate formulations.

Recent progress in dendrimer-based nanocarriers.

A large number of drug delivery systems--mostly in the form of liposomes, microspheres, nanoparticles and hydrogels--have been designed to achieve targeted delivery and sustained release of drugs by exploiting the inherent properties of polymers. The size, shape, and surface properties of the polymer are used to modulate the pharmacokinetic and pharmacodynamic behavior of drugs conjugated with or encapsulated in the polymeric carrier. Recently, a class of well-defined, monodisperse, and tree-like polymers called dendrimers has attracted attention because of the flexibility they offer in terms of their size, shape, branching, length, and surface functionality. A unique characteristic of dendrimers is that they can act as a particulate system while retaining the properties of a polymer. Drugs and diagnostic agents can be encapsulated in the central core or bound to the surface of the dendrimer by noncovalent or covalent interaction. Dendritic polymers can significantly improve pharmacokinetic and pharmacodynamic properties of low molecular weight and protein-based therapeutic agents. Furthermore, fluorescent antibodies and imaging contrast agents can be bound to these new polymers and the resulting complexes can be used for analyzing biological fluids and for diagnosis. Because of their size, shape, and ability to conjugate with a wide range of chemical entities, dendrimers have found many applications in the pharmaceutical and biomedical sciences. This review focuses on the unique carrier properties of biomimetic dendrimers and discusses a wide range of applications of dendrimers in drug delivery, including their use as drug solubilizers, absorption enhancers, release modifiers, and carriers for targeting drugs and diagnostic agents.

Drug targeting with nano-sized carrier systems.

This paper discusses the present status of, and future perspectives on, drug targeting through the bloodstream by describing the drug targeting concept, its methodologies, types of drug carriers, and recent clinical examples. This explanation and discussion is made from the viewpoint of possible correlations with studies on artificial organs, implants, and biomaterials. Two targeting methodologies (active and passive targeting), two targeting strategies (the magic bullet and the enhanced permeability and retention effect), and five types of drug carriers are explained. In addition, the clinical status of the five carrier systems is discussed.

Formulation and evaluation of diclofenac sodium buccoadhesive discs.

Twenty diclofenac sodium buccoadhesive discs containing Cp974p, polycarbophil, PEO, SCMC-medium viscosity (SCMC-MV), SCMC-ultrahigh viscosity (SCMC-UHV) or their combinations were prepared. These buccoadhesive discs were evaluated for release pattern, swelling capacity, surface pH, mucoadhesion performance, and in vitro permeation of diclofenac sodium through buccal membranes. In vivo testing of mucoadhesion time, strength of adhesion, irritation, bitterness due to drug swallowing and disc disintegration in the buccal cavity were also performed. Drug bioavailability of a selected diclofenac sodium buccoadhesive product was then compared with that of Voltarin 100 SR tablet. The percentage relative bioavailability of diclofenac sodium from the selected buccoadhesive disc 50 mg was found to be 141.31%.

Sequential oligopeptide carriers, SOCn, as scaffolds for the reconstitution of antigenic proteins: applications in solid phase immunoassays.

A new class of helicoid type sequential oligopeptide carriers (SOC), for anchoring antigenic epitopes, has been modeled from the repetitive Lys-Aib-Gly (SOC(n)-I) and Aib-Lys-Aib-Gly (SOC(n)-II) units aiming to the development of scaffolds with predetermined 3D structures. Conformational analysis showed that the SOC(n) carriers adopt 3(10)-helical structures, while the SOC(n)-conjugates retain their original active conformations and they interact neither to the carriers nor to each other. It is concluded that the helicoid structure of SOC(n) helps the reconstitution and/or mimicking of the native forms of the epitopes so that potent antigens are generated for developing specific, sensitive and reproducible immunoassays.

Active targeting with particulate drug carriers in tumor therapy: fundamentals and recent progress.

Drug therapy for the treatment of tumors is often limited by a narrow therapeutic index. One approach that overcomes this limitation is the active targeting of tumors with particulate drug carriers. The derivatization of particulate drug carriers with a ligand leads to the selective targeting of the particulate to selected cells, thereby focusing drug delivery. In addition, particulate drug carriers have a high loading capacity, do not need covalent conjugation of the drug and the formulation protects the entrapped drug from enzymatic inactivation. Despite these favorable properties, their therapeutic efficacy in animal models has been reported only in recent years. The use of internalizing ligands and the targeting of intravascular tumor cells and endothelial cells of tumor blood vessels have been instrumental in demonstrating the clinical effectiveness of particulate drug carriers in animal models. As a result, several actively targeted particulate carriers have now entered, or are about to enter, clinical investigation. Recent findings, for example, the identification of cell-penetrating peptides with restricted cell selectivity, suggest that further improvements in this approach are likely in the near future.

Targeting intracellular targets.

Many therapeutic agents have intracellular compartments as their site of action. Targeted delivery of these agents to their specific intracellular targets could result in enhanced therapeutic efficacy and reduced toxicity. Various carriers have been shown useful in targeted delivery of different classes of therapeutic agents. Among these carriers, biodegradable nanoparticles formulated from biocompatible polymers poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA) have shown the potential for sustained intracellular delivery of different therapeutic agents. In this review, we discuss different intracellular targets, barriers to intracellular delivery, mechanism and pathways of intracellular delivery, and various carriers and approaches that have been investigated for intracellular drug delivery.