Extracellularly activatable nanocarriers for drug delivery to tumors

Introduction: Nanoparticles (NPs) for drug delivery to tumors need to satisfy two seemingly conflicting requirements: they should maintain physical and chemical stability during circulation and be able to interact with target cells and release the drug at desired locations with no substantial delay. The unique microenvironment of tumors and externally applied stimuli provide a useful means to maintain a balance between the two requirements.

Areas covered: We discuss nanoparticulate drug carriers that maintain stable structures in normal conditions but respond to stimuli for the spatiotemporal control of drug delivery. We first define the desired effects of extracellular activation of NPs and frequently used stimuli and then review the examples of extracellularly activated NPs.

Expert opinion: Several challenges remain in developing extracellularly activatable NPs. First, some of the stimuli-responsive NPs undergo incremental changes in response to stimuli, losing circulation stability. Second, the applicability of stimuli in clinical settings is limited due to the occasional occurrence of the activating conditions in normal tissues. Third, the construction of stimuli-responsive NPs involves increasing complexity in NP structure and production methods. Future efforts are needed to identify new targeting conditions and increase the contrast between activated and nonactivated NPs while keeping the production methods simple and scalable.     

Expanding the Arsenal Against Huntington's Disease-Herbal Drugs and Their Nanoformulations

Huntington’s disease (HD) is an autosomal fatal genetic disease in which degeneration of neuronal cells occurs in the central nervous system (CNS). Commonly used therapeutics are cludemonoamine depletors, antipsychotics, antidepressants, and tranquilizers. However, these drugs cannot prevent the psychotic, cognitive, and behavioral dysfunctions associated with HD. In addition to this, their chronic use is limited by their long-term side effects. Herbal drugs offer a plausible alternative to this and have shown substantial therapeutic effects against HD. Moreover, their safety profile is better in terms of side effects. However, due to limited drug solubility and permeability to reach the target site, herbal drugs have not been able to reach the stage of clinical exploration. In recent years, the paradigm of research has been shifted towards the development of herbal drugs based nanoformulations that can enhance their bioavailability and blood-brain barrier permeability. The present review covers the pathophysiology of HD, available biomarkers, phytomedicines explored against HD, ongoing clinical trials on herbal drugs exclusively for treating HD and their nanocarriers, along with their potential neuroprotective effects.     

Nanostructures as Radionuclide Carriers in Auger Electron Therapy

The concept of nanoparticle-mediated radionuclide delivery in the cancer treatment has been widely discussed in the past decade. In particular, the use of inorganic and organic nanostructures in the development of radiopharmaceuticals enables the delivery of medically important radioisotopes for radionuclide therapy. In this review, we present the development of nanostructures for cancer therapy with Auger electron radionuclides. Following that, different types of nanoconstructs that can be used as carriers for Auger electron emitters, design principles, nanoparticle materials, and target vectors that overcame the main difficulties are described. In addition, systems in which high-Z element nanoparticles are used as radionuclide carriers, causing the emission of photoelectrons from the nanoparticle surface, are presented. Finally, future research opportunities in the field are discussed as well as issues that must be addressed before nanoparticle-based Auger electron radionuclide therapy can be transferred to clinical use.     

Polybutylcyanoacrylate nanocarriers as promising targeted drug delivery systems

Among the materials for preparing the polymeric nanocarriers, poly(n-butylcyanoacrylate) (PBCA), a polymer with medium length alkyl side chain, is of lower toxicity and proper degradation time. Therefore, PBCA has recently been regarded as a kind of widely used, biocompatible, biodegradable, low-toxic drug carrier. This review highlights the use of PBCA-based nanocarriers (PBCA-NCs) as targeting drug delivery systems and presents the methods of preparation, the surface modification and the advantages and limitations of PBCA-NCs. The drugs loaded in PBCA-NCs are summarized according to the treatment of diseases, and the different therapeutic applications and the most recent developments of PBCA-NCs are also discussed, which provides useful guidance on the targeting research of PBCA-NCs.     

Targeting pulmonary tuberculosis using nanocarrier-based dry powder inhalation: current status and futuristic need

Tuberculosis (TB) is a disease caused by the pathogen Mycobacterium tuberculosis. Prolonged administration of high dose antibiotics using oral and injectable routes and their associated side effects show limitations to successful treatment outcome of TB. Nanocarrier-based dry powder inhalers (DPIs) may provide a breakthrough as an alternative therapeutic approach because of their stable, non-invasive nature and ability to target the drug at the site of infection. The current review focuses on the roadmap of the respiratory system, drug deposition and targeting at the site of infection via the pulmonary route. This review will provide readers with an overview of the existing literature of nanocarrier-based DPIs of anti-TB drugs. Among different nanocarriers, results of most of the proliposomes and polymeric particles-based DPIs with respect to their characterisation parameters like encapsulation efficiency, drug loading, storage stability and aerodynamic properties are not encouraging, whereas surface engineered, nanostructured lipid carriers (NLCs), i.e. ligand attached-NLCs-based dry powder inhalers (NLCs-DPI) show promising results. But still, there is a need to investigate them for in vitro, ex vivo, in vivo and toxicity studies to achieve a market approval.     

Post‐Assembly of Oxidation‐Responsive Amphiphilic Triblock Polymer Containing a Single Diselenide

Linear amphiphilic triblock polymers containing a single diselenide (SeSe‐tri‐ABP) are synthesized by coupling reactions. They self‐assemble into spherical micelles 1 in aqueous solution. A remarkable morphology transformation of the micelles is confirmed through dynamic light scattering (DLS) and transmission electron microscopy (TEM). The release behavior of a model molecule, Rhodamine B (RB), is studied by UV–vis spectrophotometry. It is found that post‐assembly from micelles 1 to micelles 2 is induced by the oxidation‐responsive cleavage of the diselenide group in the oxidation solution. Interestingly, the RB release studies reveal that these micelles release RB in a diphasic pattern (slow after initial fast release) within 24 h under an oxidative environment. In contrast, minimal drug release (<20%) is observed within 24 h for SeSe‐tri‐ABP micelles under aqueous conditions. Meanwhile, this release behavior of the RB‐loaded micelles can be tuned by the post‐assembly of oxidation‐responsive SeSe‐tri‐ABP in different oxidation conditions, providing a promising platform for controlled delivery of nanocarriers.

     

Polymeric nanocarriers as stimuli-responsive systems for targeted tumor (cancer) therapy: Recent advances in drug delivery

In the last decade, considerable attention has been devoted to the use of biodegradable polymeric materials as potential drug delivery carriers. However, bioavailability and drug release at the disease site remain uncontrollable even with the use of polymeric nanocarriers. To address this issue, successful methodologies have been developed to synthesize polymeric nanocarriers incorporated with regions exhibiting a response to stimuli such as redox potential, temperature, pH, and light. The resultant stimuli-responsive polymeric nanocarriers have shown tremendous promise in drug delivery applications, owing to their ability to enhance the bioavailability of drugs at the disease site. In such systems, drug release is controlled in response to specific stimuli, either exogenous or endogenous. This review reports recent advances in the design of stimuli-responsive nanocarriers for drug delivery in cancer therapy. In particular, the synthetic methodologies investigated to date to introduce different types of stimuli-responsive elements within the biomaterials are described. The sufficient understanding of these stimuli-responsive nanocarriers will allow the development of a better drug delivery system that will allow us to solve the challenges encountered in targeted cancer therapy.     

细胞膜仿生纳米载体的制备及应用研究进展

由有机或无机纳米材料制备的药物载体系统广泛用于药物靶向递送和疾病的诊断治疗研究。但其存在靶向性差、体内循环时间短、生物相容性欠佳亟需提高等问题。仿生纳米药物系统是以不同种类的细胞膜修饰纳米载体,利用内源性的细胞膜提高载体的体内生物相容性、实现更精准的靶向、甚至由细胞自身的免疫原性产生免疫治疗作用。对细胞膜仿生纳米载体技术的原理、方法及其靶向机制和治疗作用作一综述,为新型给药系统研究提供思路。     

Nanocarriers for brain specific delivery of anti-retro viral drugs: challenges and achievements

HIV/AIDS is a global pandemic and the deleterious effects of human immunodeficiency virus in the brain cannot be overlooked. Though the current anti-retro viral therapy is able to reduce the virus load in the peripheral tissues of the body, the inability of the anti-retro viral drugs to cross the blood brain barrier, as such, limits its therapeutic effect in the brain. The development of newer, successful nanoparticulate drug delivery systems to enhance the feasibility of the anti-retro viral drugs to the brain, offers a novel strategy to treat the AIDS-related neuronal degradation. This review summarised the neuropathogenesis of neuroAIDS, the challenges and achievements made in the delivery of therapeutics across the BBB and the use of nanocarriers as a safe and effective way for delivering anti-retro viral drugs to the brain.