Analyzing Nanotheraputics-Based Approaches for the Management of Psychotic Disorders

Psychoses are brain disorders clinically manifested by cognitive conditions such as hallucinations, delirium, dementia, schizophrenia, and delusions. Antipsychotic drugs are associated with significant side effects such as dystonia, tardive dyskinesia, involuntary muscle movement, and metabolic disorders. Moreover, those antipsychotics currently available have poor bioavailability, drug-related adverse effects, poor therapeutic efficacy, and poor brain delivery resulting from the blood-brain barrier. Conventional dosage forms, which release the drugs into the general circulation, fail to deliver the drugs directly to the brain efficiently. Thus, a rational approach based on nanotherapeutics may overcome these limitations; such approaches can be used for the delivery of drug molecules to their targeted site. Nanotherapeutics are colloidal systems comprising nanosize-range particles and unique physicochemical properties; these properties include plasticity, biodegradability, bioacceptability, versatile surface modification properties, and protection of drug molecules from degradation. The present review describes various nanoformulations for delivery of antipsychotic drugs to the brain; these include nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsion, nanosuspensions, and carbon nanotubes. The review also considers the ability of these formulations to improve drug bioavailability and targeting affinity, as well as their ability to circumvent the first-pass metabolism.     

Nanoparticles as drug delivery systems

Controlled drug delivery systems (DDS) have several advantages compared to the traditional forms of drugs. A drug is transported to the place of action, hence, its influence on vital tissues and undesirable side effects can be minimized. Accumulation of therapeutic compounds in the target site increases and, consequently, the required doses of drugs are lower. This modern form of therapy is especially important when there is a discrepancy between the dose or the concentration of a drug and its therapeutic results or toxic effects. Cell-specific targeting can be accomplished by attaching drugs to specially designed carriers. Various nanostructures, including liposomes, polymers, dendrimers, silicon or carbon materials, and magnetic nanoparticles, have been tested as carriers in drug delivery systems. In this review, the aforementioned nanocarriers and their connections with drugs are analyzed. Special attention is paid to the functionalization of magnetic nanoparticles as carriers in DDS. Then, the advantages and disadvantages of using magnetic nanoparticles as DDS are discussed.     

Nanostructured materials in drug and gene delivery: a review of the state of the art

A wide variety of drug delivery systems have been developed, each with its own advantages and limitations, but the important goals of all of the systems are to enhance bioavailability, reduce drug toxicity, target to a particular organ, and increase the stability of the drug. The development of nanostructured drug carriers have grasped increased attention from scientific and commercial organizations due to their unique ability to deliver drugs and challenging molecules such as proteins and nucleic acids. These carriers present many technological advantages such as high carrier capacity, high chemical and biological stability, feasibility of incorporating both hydrophilic and hydrophobic substances, and their ability to be administered by a variety of routes (including oral, inhalational, and parenteral) to provide controlled/sustained drug release. Moreover, applications of nanoparticulate formulations in enhancing drug solubility, dissolution, bioavailability, safety, and stability have already been proven. In the view of their multifaceted applications, the present review aims to discuss and summarize some of the interesting findings and applications, methods of preparation, and characterization of various nanostructured carriers useful in drug delivery. Included in this discussion are polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, dendrimers, cyclodextrins, fullerenes, gold and silica nanoparticles, and quantum dots. Because there are likely to be new applications for nanoparticles in drug delivery, they are expected to solve many problems associated with the delivery of drugs and biomolecules through different delivery routes.     

Status of novel drug delivery technology for phytotherapeutics

Herbal medicines have been widely used all over the world since ancient times and have been recognized by physicians and patients for their better therapeutic value as they have fewer adverse effects as compared with modern medicines. However, phytotherapeutics needs a scientific approach to deliver the components in a sustained manner to increase patient compliance and avoid repeated administration. This can be achieved by designing novel drug delivery systems for herbal constituents. Novel drug delivery systems not only reduce the repeated administration to overcome non-compliance, but also help to increase the therapeutic value by reducing toxicity and increasing the bioavailability, and so on. Recently, pharmaceutical scientists have shifted their focus to designing a drug delivery system for herbal medicines using a scientific approach. For a long time herbal medicines were not considered for development as novel formulations owing to lack of scientific justification and processing difficulties, such as standardization, extraction and identification of individual drug components in complex polyherbal systems. However, modern phytopharmaceutical research solves the scientific needs for herbal medicines as in modern medicine, which gives way for developing novel formulations such as nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, solid lipid nanoparticles, and so on. This article summarizes various drug delivery technologies for herbal actives, which are gaining more attention for better therapeutic response.     

从纳米给药系统角度探讨阿尔茨海默病的治疗策略

阿尔茨海默病严重威胁人类健康,主要是血脑屏障限制了药物到达作用靶点,影响阿尔茨海默病的治疗.而纳米给药系统为药物的脑靶向递送提供了可能,对阿尔茨海默病的治疗有改善作用,本文从阿尔茨海默病的发病机制和常规治疗药物展开,重点从纳米给药系统角度进行介绍阿尔茨海默病的治疗策略,概述几种典型的治疗阿尔茨海默病的纳米给药系统,即脂质体、聚合物胶束、固体脂质纳米粒和聚合物纳米粒等.     

Nano carriers for drug transport across the blood–brain barrier

Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood–brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug–carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully discussed.     

Strategies for delivering local anesthetics to the skin: focus on liposomes,solid lipid nanoparticles,hydrogels and patches

Introduction: Dermal and transdermal drug delivery systems offer the possibility to control the release of the drug for an extended period of time. In particular, skin-delivery of local anesthetics (LA) is one of the most important strategies to increase the local drug concentration and to reduce systemic adverse reactions.

Areas covered: During the development phase of new formulations for skin-delivery of LA one should consider a set of desirable features such providing suitable adhesion, easy application/removal and also to be biocompatible, biodegradable and non-toxic. This review emphasizes the main strategies for skin-delivery of LA considering those features in relation to the composition of the delivery systems described. The topics highlight the relationships between physico-chemical studies and pharmaceutical applications for liposomes and solid lipid nanoparticles as well as the formulation and clinical applications for hydrogels and patches.

Expert opinion: The development of LA skin-delivery systems using hydrogels and different permeation enhancers, liposomes or lipid nanoparticles (as isolated carrier systems or as their dispersion in a gel-base) and patches have been explored as alternatives to commercial formulations, modifying the release rate of LA, increasing bioadhesive properties and reducing toxicity, resulting in an improved therapeutic efficacy. This review should provide to the reader a special emphasis on four delivery-systems, comprising the group of liposomes and lipid nanoparticles, hydrogels and patches technologies looking forward their application for skin anesthesia.     

载药金纳米粒的研究进展

近年来,作为一种新型药物递送系统,金纳米粒已引起了广泛关注。由于其特殊的物理化学性质,能与多种类型药物发生相互作用,如蛋白质、核酸、小分子药物等,从而可应用于肿瘤治疗和检测。笔者对载药金纳米粒的制备方法、载药方式和安全性等问题进行综述。     

Nanoparticle-based diagnosis and therapy

Nanoparticles are at the leading edge of the rapidly developing field of material science in nanotechnology with many potential applications in clinical medicine and research. Due to their unique size-dependent properties nanoparticles offer the possibility to develop both new therapeutic and diagnostic tools. The ability to incorporate drugs into nanosystems displays a new paradigm in pharmacotherapy that could be used for cell-targeted drug delivery. Nontargeted nanosystems such as nanocarriers that are coated with polymers or albumin and solid lipid particles have been used to transport a large number of compounds. However, nowadays drugs can be coupled to nanocarriers that are specific for cells and/or organs. Thus, drugs that are either trapped within the carriers or deposited in subsurface oil layers could be specifically delivered to organs, tumors and cells. These strategies can be used to concentrate drugs in selected target tissues thus minimizing systemic side effects and toxicity. In addition to these therapeutic options, nanoparticle-based "molecular" imaging displays a field in which this new technology has set the stage for an evolutionary leap in diagnostic imaging. Based on the recent progress in nanobiotechnology, nanoparticles have the potential to become useful tools as therapeutic and diagnostic tools in the near future.     

天然药物靶向给药系统的研究

采用新型药物载体使天然药物具有靶向作用是近年来药剂学的研究热点之一。综述脂质体、纳米粒、微球、微乳、药质体等新型载体在天然药物靶向给药系统研究中的应用,并介绍膜融合脂质体、纳米脂质载体、药脂结合物纳米粒以及分泌颗粒类似物等几种新型靶向给药系统的药物载体。     

Lipid nanoparticles as novel delivery systems for cosmetics and dermal pharmaceuticals

INTRODUCTION: Lipid nanoparticles are innovative carrier systems developed as an alternative to traditional vehicles such as emulsions, liposomes and polymeric nanoparticles. Solid lipid nanoparticles (SLN) and the newest nanostructured lipid carriers (NLC) show important advantages for dermal application of cosmetics and pharmaceuticals. AREA COVERED: This article focuses on the main features of lipid nanoparticles, in terms of their preparation and recent advancements. A detailed review of the literature is presented, introducing the importance of these systems in the topical delivery of drugs and active substances. EXPERT OPINION: Lipid nanoparticles are able to enhance drug penetration into the skin, allowing increased targeting to the epidermis and consequently increasing treatment efficiency and reducing the systemic absorption of drugs and cosmetic actives. The complete biodegradation of lipid nanoparticles and their biocompatible chemical nature have secured them the title of 'nanosafe carriers.' SLN and NLC represent a new technological era, which has been taken over by the cosmetic and pharmaceutical industry, which will open new channels for effective topical delivery of substances.     

Polysaccharide-based nanoparticles: a versatile platform for drug delivery and biomedical imaging

Polysaccharide-based nanoparticles have attracted interest as carriers for imaging and therapeutic agents because of their unique physicochemical properties, including biocompatibility and biodegradability. In addition, the functional groups of the polysaccharide backbone allow facile chemical modification to develop nanoparticles with diverse structures. Some polysaccharides have the intrinsic ability to recognize specific cell types, facilitating the design of targeted-drug delivery systems through receptor-mediated endocytosis. The main objective of this review is to provide an overview of various polysaccharide-based nanoparticles and to highlight the recent efforts that have been made to improve the characteristics of polysaccharide-based nanoparticles for drug delivery and biomedical imaging.     

Application of lipid nanoparticles to ocular drug delivery

ABSTRACT

Introduction: Although eye drops are widely used as drug delivery systems for the anterior segment of the eye, they are also associated with poor drug bioavailability due to transient contact time and rapid washout by tearing. Moreover, effective drug delivery to the posterior segment of the eye is challenging, and alternative routes of administration (periocular and intravitreal) are generally needed, the blood–retinal barrier being the major obstacle to systemic drug delivery.

Areas covered: Nanotechnology, and especially lipid nanoparticles, can improve the therapeutic efficiency, compliance and safety of ocular drugs, administered via different routes, to both the anterior and posterior segment of the eye. This review highlights the main ocular barriers to drug delivery, as well as the most common eye diseases suitable for pharmacological treatment in which lipid nanoparticles have proved efficacious as alternative delivery systems.

Expert opinion: Lipid-based nanocarriers are among the most biocompatible and versatile means for ocular delivery. Mucoadhesion with consequent increase in pre-corneal retention time, and enhanced permeation due to cellular uptake by corneal epithelial cells, are the essential goals for topical lipid nanoparticle delivery. Gene delivery to the retina has shown very promising results after intravitreal administration of lipid nanoparticles as non-viral vectors.     

Liposomal nanomedicines

Liposomal nanoparticles (LNs) encapsulating therapeutic agents, or liposomal nanomedicines, represent an advanced class of drug delivery systems, with several formulations presently on the market and many more in clinical trials. Over the past 20 years, a variety of techniques have been developed for encapsulating both conventional drugs (such as anticancer drugs and antibiotics) and the new genetic drugs (plasmid DNA containing therapeutic genes, antisense oligonucleotides and small interfering RNA) within LNs. If the LNs possess certain properties, they tend to accumulate at sites of disease, such as tumours, where the endothelial layer is ‘leaky’ and allows extravasation of particles with small diameters. These properties include a diameter centred on 100 nm, a high drug-to-lipid ratio, excellent retention of the encapsulated drug, and a long (> 6 h) circulation lifetime. These properties permit the LNs to protect their contents during circulation, prevent contact with healthy tissues, and accumulate at sites of disease. The authors discuss recent advances in this field involving conventional anticancer drugs, as well as applications involving gene delivery, stimulation of the immune system and silencing of unwanted gene expression. Liposomal nanomedicines have the potential to offer new treatments in such areas as cancer therapy, vaccine development and cholesterol management.     

The potential of chitosan in ocular drug delivery

This paper presents an overview of the potential of chitosan-based systems for improving the retention and biodistribution of drugs applied topically onto the eye. Besides its low toxicity and good ocular tolerance, chitosan exhibits favourable biological behaviour, such as bioadhesion- and permeability-enhancing properties, and also interesting physico-chemical characteristics, which make it a unique material for the design of ocular drug delivery vehicles. The review summarizes the techniques for the production of chitosan gels, chitosan-coated colloidal systems and chitosan nanoparticles, and describes their mechanism of action upon contact with the ocular mucosa. The results reported until now have provided evidence of the potential of chitosan gels for enhancing and prolonging the retention of drugs on the eye surface. On the other hand, chitosan-based colloidal systems were found to work as transmucosal drug carriers, either facilitating the transport of drugs to the inner eye (chitosan-coated colloidal systems containing indometacin) or their accumulation into the corneal/conjunctival epithelia (chitosan nanoparticles containing ciclosporin). Finally, the tolerance, toxicity and biodegradation of the carriers under evaluation were reviewed.     

Exploitation of lipid-polymeric matrices at nanoscale for drug delivery applications

ABSTRACT

Introduction: Progress in drug delivery and a better quality of life for patients, relies on the development of new and suitable drug carrier systems, with unequivocal therapeutic benefits, low systemic toxicity and reduced side effects. Lipid-polymeric nanoparticles have been explored to produce nanocarriers due to their features and applications such as high drug entrapment, physical-chemical stability and controlled release properties.

Areas covered: In this review, we describe several hybrid nanoparticles obtained from mixing a polymer with a lipid matrix. This association can potentiate the efficacy of drug delivery systems, due to the enhancement of encapsulation efficiency and loading capacity, tailoring the drug release according to the therapeutic purpose, and improving the drug uptake by targeting it to specific receptors. Contrary to lipid nanoparticles, these hybrid nanoparticles can decrease the initial burst release and promote a more sustained and localized release of the drug.

Expert Opinion: Lipid-polymeric nanoparticles are versatile vehicles for drug delivery by different administration routes in the treatment of multiple diseases. Different solid lipids, polymers, surfactants and techniques for producing these carriers have been investigated, revealing the importance of their composition to achieve optimal characteristics to drug delivery.     

Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles

In this review, we focus on the biophysics of cell membrane lipids, particularly when cancers develop acquired drug resistance, and how biophysical changes in resistant cell membrane influence drug transport and nanoparticle-mediated drug delivery. Recent advances in membrane lipid research show the varied roles of lipids in regulating membrane P-glycoprotein function, membrane trafficking, apoptotic pathways, drug transport, and endocytic functions, particularly endocytosis, the primary mechanism of cellular uptake of nanoparticle-based drug delivery systems. Since acquired drug resistance alters lipid biosynthesis, understanding the role of lipids in cell membrane biophysics and its effect on drug transport is critical for developing effective therapeutic and drug delivery approaches to overcome drug resistance. Here we discuss novel strategies for (a) modulating the biophysical properties of membrane lipids of resistant cells to facilitate drug transport and regain endocytic function and (b) developing effective nanoparticles based on their biophysical interactions with membrane lipids to enhance drug delivery and overcome drug resistance.     

Disposition of nanoparticle-based delivery system via inner ear administration

The inner ear is difficult to access by conventional systemic drug delivery due to formidable physiological and anatomic barriers. There is an increasing interest in the treatment of inner ear disorders by topical application of drugs to the inner ear. One of the most important issues to overcome before full clinical application is the development of smart delivery systems for drugs to the target sites and controlled release in the inner ear. This is an area where nanoparticles will play an extremely important role. These submicron particles have exhibited improved biocompatibility, in vivo stability, target specificity, and cell/tissue uptake and internalization of the encapsulated therapeutic agents, leading to a decrease in the dose required and a decrease in side effects. This unique combination of properties makes nanoparticles a novel delivery device, which fulfils the requirements for inner ear application. This review will summarize recent findings and applications of various nanoparticle-based systems like poly (D, L-lactic/glycolic acid) nanoparticles, magnetic nanoparticles, lipid nanoparticles, liposomes, polymersomes, hydroxyapatite nanoparticles, and silica nanoparticles in the field of inner ear drug delivery. Moreover, the review will provide an insight into the future strategies of nanoparticle-based cochlear drug delivery. In conjunction, physiological considerations related to inner ear administration will be highlighted. The routes and applications for local inner-ear drug delivery will also be mentioned. In closing, this review will give an overview of the potential future development in inner ear administration with nanoparticles.     

The performance of nanocarriers for transmucosal drug delivery

Most of the newly designed drug molecules are characterised by low solubility in aqueous medium, low permeability through biological membranes and/or an insufficient stability in the biological environment. Fundamental studies have provided proof-of-concept of the potential of particulate nanocarriers for overcoming these unsuitable properties. For example, it is known that polymeric nanosystems may enhance transmucosal transport of drugs with poor penetration capacities while preserving their biological activity. Moreover, in recent years it has become clear that through an appropriate selection of the nanosystem components it is possible to enhance its affinity for the mucosa and, hence, the residence time of the drug in contact with the absorptive epithelium. These properties, combined with a suitably tailored release profile can markedly increase the efficacy of pharmaceuticals. Overall, the properties that have been identified as critical for the performance of these delivery systems are particle size, surface charge and surface chemical composition. These properties are known to affect the physical and chemical stability of the nanoparticles in the biological environment as well as their ability to interact (unspecific bioadhesion, receptor-mediated interaction and so on) and, eventually, overcome biological barriers. The present article aims to critically review the latest advances in this area and to provide some insights into these complex issues. Thus, herein the most widely investigated transmucosal drug delivery nanosystems and their most promising applications are reported.     

RETRACTED: Pulmonary route of administration is instrumental in developing therapeutic interventions against respiratory diseases

Pulmonary route of drug delivery has drawn significant attention due to the limitations associated with conventional routes and available treatment options. Drugs administered through pulmonary route has been an important research area that focuses on to developing effective therapeutic interventions for asthma, chronic obstructive pulmonary disease, tuberculosis, lung cancer etc. The intravenous route has been a natural route of delivery of proteins and peptides but associated with several issues including high cost, needle-phobia, pain, sterility issues etc. These issues might be addressed by the pulmonary administration of macromolecules to achieving an effective delivery and efficacious therapeutic impact. Efforts have been made to develop novel drug delivery systems (NDDS) such as nanoparticles, microparticles, liposomes and their engineered versions, polymerosomes, micelles etc to achieving targeted and sustained delivery of drug(s) through pulmonary route. Further, novel approaches such as polymer-drug conjugates, mucoadhesive particles and mucus penetrating particles have attracted significant attention due to their unique features for an effective delivery of drugs. Also, use of semi flourinated alkanes is in use for improvising the pulmonary delivery of lipophilic drugs. Present review focuses on to unravel the mechanism of pulmonary absorption of drugs for major pulmonary diseases. It summarizes the development of interventional approaches using various particulate and vesicular drug delivery systems. In essence, the orchestrated attempt presents an inflammatory narrative on the advancements in the field of pulmonary drug delivery.