Technical and engineering considerations for designing therapeutics and delivery systems.

The newly-emerged pathological conditions and increased rates of drug resistance necessitate application of the state-of-the-art technologies for accelerated discovery of the therapeutic candidates and obtaining comprehensive knowledge about their targets, action mechanisms, and interactions within the body including those between the receptors and drugs. Using the physics- and chemistry-based modern techniques for theranostic purposes, preparing smart carriers, local delivery of genes or drugs, and enhancing pharmaceutical bioavailability could be of great value against the hard-to-treat diseases and growing drug resistance. Besides the artificial intelligence- and quantum-based techniques, crystal engineering capable of designing new molecules with appropriate characteristics, improving the stability and bioavailability of poorly soluble drugs, and efficient carrier development could play a crucial role in manufacturing efficient pharmaceuticals and reducing the adverse events. In this context, identifying the structures and behaviors of crystals and predicting their characteristics are of great value. Electron diffraction by accelerated analysis of the chemicals and sensitivity to charge alterations, electromechanical tools for controlled delivery of therapeutics, mechatronics via fabrication of multi-functional smart products including the organ-on-chip devices for healthcare applications, and optomechatronics by overcoming the limitations of conventional biomedical techniques could address the unmet biomedical requirements and facilitate development of more effective theranostics with improved outcomes.

Nanobionics: From plant empowering to the infectious disease treatment.

Infectious diseases (ID) are serious threats against the global health and socio-economic conditions. Vaccination usually plays a key role in disease prevention, however, insufficient efficiency or immunogenicity may be quite challenging. Using the advanced vectors for delivery of vaccines with suitable efficiency, safety, and immune-modulatory activity, and tunable characteristics could be helpful, but there are no systematic reviews confirming the capabilities of the vaccine delivery systems for covering various types of pathogens. Furthermore, high rates of the infections, transmission, and fatal ratio and diversity of the pathogens and infection mechanisms may negatively influence vaccine effectiveness. The absence of highly-effective antibiotics against the resistant strains of bacteria and longevity of antibiotic testing have provoked increasing needs towards the application of more accurate and specific theranostic strategies including the nanotechnology-based ones. Nanobionics which is based on the charge storage and transport in the molecular structures, could be of key value in the molecular diagnostic tests and highly-specific electro-analytical methods or devices. Such devices based on the early disease diagnostics might be of critical significance against various types of diseases. This article highlights the significance of nanobionics against ID.

Presenting a bioactive nanotherapeutic agent for colon cancer treatment.

Colon cancer (CC) is one of the major causes of death worldwide. Insufficient drug concentration, non-specificity, or serious adverse effects of the conventional chemotherapeutic agents necessitate application of more effective treatment options. Herein, poly-ursolic acid, a polymer with anticancer effect, has been self-assembled for producing nanoparticles (NPs) for delivery of irinotecan (IRN) which is usually associated with poor solubility and severe adverse effects. NPs showed therapeutic efficiency by themselves in vivo and in vitro. IRN-loaded NPs with appropriate physicochemical characteristics, released IRN in a controlled fashion and demonstrated more efficient cytotoxicity, lower clearance rate and distribution volume, higher Cmax and AUC, prolonged t1/2, increased accumulation in tumor, and therapeutic effects in vivo as compared to free drug. There was no significant alteration of body weight or damage to the major organs. The prepared bioactive nanoplatform via improvement of IRN efficiency could be applied for inducing synergistic toxicity against CC.

Development of a novel nanoformulation against the colorectal cancer.

Colorectal cancer (CRC) with high metastasis rates has been known as a major cause of death worldwide. Lack of the specificity and insufficient concentrations of traditional chemotherapeutics at tumor site and their severe adverse effects necessitate development of new treatment strategies such as designing suitable nanocarriers for delivery of drugs, improving their pharmacological profiles and reducing adverse effects. We have developed a platform based on the poly-ursolic acid (poly-UA), a polymeric system with potential anticancer effect. Following the self-assembly of poly-UA into the nanoparticles (NPs), they were applied for delivery of mithramycin A (Mith-A), a promising candidate for CRC therapy, however, with some limitations such as rapid clearance and serious side effects. Mith-A-loaded poly-UA NPs with suitable physicochemical properties and efficient drug entrapment, released Mith-A in a controlled manner and provided suitable toxicity against the CT-26 colorectal cancer cells, increased accumulation in tumor, and protection against the detrimental features of the disease. Poly-UA NPs demonstrated therapeutic efficiency (in vivo and in vitro) by themselves. The prepared NPs induced no remarkable alteration of body weights or damages to the major organs in animals bearing tumor indicating the safety of NPs. The bioactive nanoformulation along with improving the pharmacological profile of Mith-A could provide a synergistic toxicity against the CRC.

The biomedical significance of multifunctional nanobiomaterials: The key components for site-specific delivery of therapeutics.

The emergence of nanotechnology has provided the possibilities to overcome the potential problems associated with the development of pharmaceuticals including the low solubility, non-specific cellular uptake or action, and rapid clearance. Regarding the biomaterials (BMs), huge efforts have been made for improving their multi-functionalities via incorporation of various nanomaterials (NMs). Nanocomposite hydrogels with suitable properties could exhibit a variety of beneficial effects in biomedicine particularly in the delivery of therapeutics or tissue engineering. NMs including the silica- or carbon-based ones are capable of integration into various BMs that might be due to their special compositions or properties such as the hydrophilicity, hydrophobicity, magnetic or electrical characteristics, and responsiveness to various stimuli. This might provide multi-functional nanobiomaterials against a wide variety of disorders. Meanwhile, inappropriate distribution or penetration into the cells or tissues, bio-nano interface complexity, targeting ability loss, or any other unpredicted phenomena are the serious challenging issues. Computational simulations and models enable development of NMs with optimal characteristics and provide a deeper knowledge of NM interaction with biosystems. This review highlights the biomedical significance of the multifunctional NMs particularly those applied for the development of 2-D or 3-D BMs for a variety of applications including the site-specific delivery of therapeutics. The powerful impacts of the computational techniques on the design process of NMs, quantitation and prediction of protein corona formation, risk assessment, and individualized therapy for improved therapeutic outcomes have also been discussed.

The significance of bioengineered nanoplatforms against SARS-CoV-2: From detection to genome editing.

COVID-19 outbreak can impose serious negative impacts on the infrastructures of societies including the healthcare systems. Despite the increasing research efforts, false positive or negative results that may be associated with serologic or even RT-PCR tests, inappropriate or variable immune response, and high rates of mutations in coronavirus may negatively affect virus detection process and effectiveness of the vaccines or drugs in development. Nanotechnology-based research attempts via developing state-of-the-art techniques such as nanomechatronics ones and advanced materials including the sensors for detecting the pathogen loads at very low concentrations or site-specific delivery of therapeutics, and real-time protections against the pandemic outbreaks by nanorobots can provide outstanding biomedical breakthroughs. Considering the unique characteristics of pathogens particularly the newly-emerged ones and avoiding the exaggerated optimism or simplistic views on the prophylactic and therapeutic approaches including the one-size-fits-all ones or presenting multiple medications that may be associated with synergistic toxicities rather than enhanced efficiencies might pave the way towards the development of more appropriate treatment strategies with reduced safety concerns. This paper highlights the significance of nanoplatforms against the viral disorders and their capabilities of genome editing that may facilitate taking more appropriate measures against SARS-CoV-2.

The capabilities of nanoelectronic 2-D materials for bio-inspired computing and drug delivery indicate their significance in modern drug design.

Remarkable advancements in the computational techniques and nanoelectronics have attracted considerable interests for development of highly-sophisticated materials (Ms) including the theranostics with optimal characteristics and innovative delivery systems. Analyzing the huge amounts of multivariate data and solving the newly-emerged complicated problems including the healthcare-related ones have created increasing demands for improving the computational speed and minimizing the consumption of energy. Shifting towards the non-von Neumann approaches enables performing specific computational tasks and optimizing the processing of signals. Besides usefulness for neuromorphic computing and increasing the efficiency of computation energy, 2-D electronic Ms are capable of optical sensing with ultra-fast and ultra-sensitive responses, mimicking the neurons, detection of pathogens or biomolecules, and prediction of the progression of diseases, assessment of the pharmacokinetics/pharmacodynamics of therapeutic candidates, mimicking the dynamics of the release of neurotransmitters or fluxes of ions that might provide a deeper knowledge about the computations and information flow in the brain, and development of more effective treatment protocols with improved outcomes. 2-D Ms appear as the major components of the next-generation electronically-enabled devices for highly-advanced computations, bio-imaging, diagnostics, tissue engineering, and designing smart systems for site-specific delivery of therapeutics that might result in the reduced adverse effects of drugs and improved patient compliance. This manuscript highlights the significance of 2-D Ms in the neuromorphic computing, optimizing the energy efficiency of the multi-step computations, providing novel architectures or multi-functional systems, improved performance of a variety of devices and bio-inspired functionalities, and delivery of theranostics.

Coating of ferulic acid-loaded silk fibroin nanoparticles with neutrophil membranes: A promising strategy against the acute pancreatitis.

Nanotechnology-based approaches have enabled overcoming the challenging issues such as the rapid clearance, poor solubility, and non-specific action or cellular uptake of drugs. In this study, we have evaluated the therapeutic effects of the phenolic compound, ferulic acid (FA), in the acute pancreatitis (AP) as this phenolic compound has demonstrated promising effects against the oxidative stress and inflammatory reactions. In order to overcome the poor solubility and bioavailability of FA, it was entrapped into the nanoparticles (NPs) based on the silk fibroin (SF) as a biomimetic substance. Neutrophil membrane-coated SF-NPs with appropriate capacity of FA loading and physicochemical characteristics, released FA in a controlled fashion, selectively delivered FA into the inflammatory pancreas lesion, and demonstrated protective effects against the detrimental aspects of the disease. The prepared nanoformulation by improving the pharmacological profile of FA and targeted delivery could be of therapeutic importance against the AP via suppressing the inflammation and oxidative stress.

Nanotheranostics against COVID-19: From multivalent to immune-targeted materials.

Destructive impacts of COVID-19 pandemic worldwide necessitates taking more appropriate measures for mitigating virus spread and development of the effective theranostic agents. In general, high heterogeneity of viruses is a major challenging issue towards the development of effective antiviral agents. Regarding the coronavirus, its high mutation rates can negatively affect virus detection process or the efficiency of drugs and vaccines in development or induce drug resistance. Bioengineered nanomaterials with suitable physicochemical characteristics for site-specific therapeutic delivery, highly-sensitive nanobiosensors for detection of very low virus concentration, and real-time protections using the nanorobots can provide roadmaps towards the imminent breakthroughs in theranostics of a variety of diseases including the COVID-19. Besides revolutionizing the classical disinfection procedures, state-of-the-art nanotechnology-based approaches enable providing the analytical tools for accelerated monitoring of coronavirus and associated biomarkers or drug delivery towards the pulmonary system or other affected organs. Multivalent nanomaterials capable of interaction with multivalent pathogens including the viruses could be suitable candidates for viral detection and prevention of further infections. Besides the inactivation or destruction of the virus, functionalized nanoparticles capable of modulating patient's immune response might be of great significance for attenuating the exaggerated inflammatory reactions or development of the effective nanovaccines and medications against the virus pandemics including the COVID-19.

Towards the quantum-enabled technologies for development of drugs or delivery systems.

Enormous advances in technology and science have provided outstanding innovations including the development of quantum computers (QCs) capable of performing various tasks much more efficiently and quickly than the classical computers. Integrating and analyzing gigantic amounts of data, ultra-rapid calculations, solving intractable problems, secure communications, providing novel insights into the material design or biosystems, advanced simulations, rapid genome analysis and sequencing, early cancer detection, identifying novel drug applications, accelerated discovery of new molecules, targets, or theranostic agents and evaluation of their behaviors, and acquiring a deeper knowledge about the complex data patterns, formation of proteins, or mechanism of disease progression and evolution by QCs may indeed revolutionize conventional technologies and strategies. Application of quantum computing and machine learning for accelerated analysis of the biological or medical data, uncovering the mechanisms of chemical reactions or action of drug candidates, and creation of patient-specific treatment strategies using genomics data can result in the development of more effective and less toxic drugs or personalized therapy. This article highlights the importance of QCs in designing drugs and delivery systems, limitations, and possible solutions.

The significance of artificial intelligence in drug delivery system design.

Over the last decade, increasing interest has been attracted towards the application of artificial intelligence (AI) technology for analyzing and interpreting the biological or genetic information, accelerated drug discovery, and identification of the selective small-molecule modulators or rare molecules and prediction of their behavior. Application of the automated workflows and databases for rapid analysis of the huge amounts of data and artificial neural networks (ANNs) for development of the novel hypotheses and treatment strategies, prediction of disease progression, and evaluation of the pharmacological profiles of drug candidates may significantly improve treatment outcomes. Target fishing (TF) by rapid prediction or identification of the biological targets might be of great help for linking targets to the novel compounds. AI and TF methods in association with human expertise may indeed revolutionize the current theranostic strategies, meanwhile, validation approaches are necessary to overcome the potential challenges and ensure higher accuracy. In this review, the significance of AI and TF in the development of drugs and delivery systems and the potential challenging issues have been highlighted.

Ignoring the modeling approaches: Towards the shadowy paths in nanomedicine.

Limited efficiency of the conventional therapeutic options against a variety of diseases has provoked nanotech-based research efforts to develop advanced materials and devices for targeted delivery of theranostics which may provide imminent breakthroughs in medicine. However, nonspecific distribution or inappropriate tissue penetration of nanoparticles, complexity of drug delivery process, insufficient drug accumulation, loss of targeting ability, occurrence of the unexpected phenomena, safety concerns, and data reliability have remained challenging. Indeed, translation of nanotechnology-based products to the clinical applications necessitates the rigorous consideration of the challenging issues associated with currently available nanoformulations. Computational models and simulations which enable to design the nanoparticles with optimized properties along with method validation, provide fundamental knowledge about the complex interaction of nanomaterials with environmental or biological systems, and predict the pharmacological profile of nanomaterials, should constitute a key part of the innovative drug delivery research leading to the maximal efficacy and minimal safety concerns. This review highlights the importance of computational modeling in the development of efficient nanotherapeutic delivery systems.

Tissue engineering: Still facing a long way ahead.

Tissue engineering (TE) has provided promising perspectives to overcome the limited efficiency of the conventional treatment options or organ transplantation. Considerable advances in stem cell therapies and biomaterials science and development of delivery systems capable to mimic the production of growth factors may offer treatment breakthroughs in a variety of diseases. Meanwhile, proper vascularization, creation of the complex tissues, tissue quality, functional integration between the graft and host tissues, and the potential risks of chromosomal instability, mutations, tumorigenesis, or unexpected events have remained challenging. Furthermore, the promising results of the in vitro or in vivo studies may not be applicable to the clinical settings. These issues remind us to avoid the simplistic views or exaggerated optimism regarding the novel technologies including TE. This review highlights the advances in TE including its promising potential for clinical applications and the potential solutions for common pitfalls with a special look at the role of the computational modeling that may facilitate translation of the basic research findings into the clinical applications.

Linkers: The key elements for the creation of efficient nanotherapeutics.

The limited efficiency of the conventional treatment options against a variety of disorders have created demands towards the development of more efficient theranostic strategies. Advances in nanomedicine have provided promising perspectives for the treatment of hard-to-treat diseases. Application of the high-resolution imaging, multifunctional nanoparticles, and a wide variety of nanodevices for early diagnosis of disease, promoting tissue regeneration, and targeted delivery of therapeutic agents, may result in minimal side effects and improved treatment outcome. Meanwhile, a number of nanotherapeutics have shown poor efficiency that might be due to a variety of factors including the inappropriate design protocols or nonspecific drug release. Selective cell targeting and controlled drug release are the key elements which should be considered in designing the nanocarriers for targeted delivery of therapeutic agents. Linkers, the essential components incorporated in the building blocks of drug delivery systems, provide the stability, high payloads, targeted drug delivery, and controlled release, hence, they might be critically involved in the nanotherapeutic activity. In the present review, the significance of linkers in the development of effective drug delivery systems has been highlighted.

Ferulic acid-loaded nanostructured lipid carriers: A promising nanoformulation against the ischemic neural injuries.

AIMS: Treatment of the ischemic stroke has remained a major healthcare challenge. The phenolic compound, ferulic acid (FA), has shown promising antioxidant and neuroprotective effects, however, low bioavailability may negatively affect its efficiency. This, prompted us to incorporate FA into the nanostructured lipid carriers (FA-NLCs) and evaluate its therapeutic potential in in vitro and in vivo models of ischemic stroke. MAIN METHODS: FA-NLCs were prepared by high-pressure homogenization followed by physicochemical characterization, evaluation of the bioactivity of FA-NLCs in oxygen-glucose deprivation (OGD) and global cerebral ischemia/reperfusion (I/R) injury and implication of phosphatidylinositol 3-kinase (PI3K) pathway in this regard. KEY FINDINGS: Formation of FA-NLCs which exhibited a controlled release profile, was confirmed by scanning electron microscope and differential scanning calorimetry. 1- and 8-h OGD followed by 24h re-oxygenation significantly reduced PC12 cell viability, increased lactate dehydrogenase activity and number of condensed nuclei, and induced oxidative stress as revealed by increased malondialdehyde and decreased glutathione content and superoxide dismutase and catalase activities. FA (80 and 100µM) reduced the cytotoxicity, oxidative stress, and cellular damage only after 1-h OGD, while, FA-NLCs (containing 80 and 100µM of FA) were effective at both time points. Intravenous injections of FA-NLCs (20 and 25mg/kg) into rats significantly attenuated I/R-induced neurobehavioural deficits, cellular damage, and oxidative stress, while, FA failed. Pre-treatment with PI3K inhibitor, LY294002, abolished the protective effects against OGD or I/R. SIGNIFICANCE: FA-NLCs by improving the pharmacological profile of FA and activating PI3K pathway might be of therapeutic value in cerebral stroke.

Application of nanostructured lipid carriers: the prolonged protective effects for sesamol in in vitro and in vivo models of ischemic stroke via activation of PI3K signalling pathway.

BACKGROUND: Treatment of the ischemic stroke has remained a major healthcare challenge. The phenolic compound, sesamol, has shown promising antioxidant and neuroprotective effects, however, fast clearance may negatively affect its efficiency. This, prompted us to incorporate sesamol into the nanostructured lipid carriers (S-NLCs) and evaluate its therapeutic potential in in vitro and in vivo models of ischemic stroke. METHODS: S-NLCs formulations were prepared by high-pressure homogenization followed by physicochemical characterization, evaluation of the bioactivity of the optimal formulation in oxygen-glucose deprivation (OGD) and global cerebral ischemia/reperfusion (I/R) injury and implication of phosphatidylinositol 3-kinase (PI3K) pathway in this regard. Two- or three-way ANOVA, Mann-Whitney U test, and Student's t-test were used for data analysis. RESULTS: Formation of S-NLCs which exhibited a controlled release profile, was confirmed by scanning electron microscope and differential scanning calorimetry. 1- and 8-h OGD followed by 24 h re-oxygenation significantly reduced PC12 cell viability, increased lactate dehydrogenase activity and the number of condensed nuclei, and induced oxidative stress as revealed by increased malondialdehyde level and decreased glutathione content and superoxide dismutase and catalase activities. Sesamol (80 and 100 µM) reduced the cytotoxicity, oxidative stress, and cellular damage only after 1-h OGD, while, S-NLCs (containing 80 and 100 µM of sesamol) were effective at both time points. Intravenous injections of S-NLCs (20 and 25 mg/kg) into rats markedly attenuated I/R-induced neurobehavioural deficits, cellular damage, and oxidative stress, while, free sesamol failed. Pre-treatment with PI3K inhibitor, LY294002, abolished the protective effects against OGD or I/R. CONCLUSIONS: S-NLCs improve the pharmacological profile of sesamol and provide longer lasting protective effects for this phenolic phytochemical. This nanoformulation by activating PI3K pathway may serve as a promising candidate for neuroprotection against the cerebral stroke or other neurodegenerative disorders. Sesamol-loaded NLCs, a promising nanoformulation against the ischemic stroke.

Application of modelling and nanotechnology-based approaches: The emergence of breakthroughs in theranostics of central nervous system disorders.

The limited efficiency of the current treatment options against the central nervous system (CNS) disorders has created increasing demands towards the development of novel theranostic strategies. The enormous research efforts in nanotechnology have led to the production of highly-advanced nanodevices and biomaterials in a variety of geometries and configurations for targeted delivery of genes, drugs, or growth factors across the blood-brain barrier. Meanwhile, the richness or reliability of data, drug delivery methods, therapeutic effects or potential toxicity of nanoparticles, occurrence of the unexpected phenomena due to the polydisperse or polymorphic nature of nanomaterials, and personalized theranostics have remained as challenging issues. In this respect, computational modelling has emerged as a powerful tool for rational design of nanoparticles with optimized characteristics including the selectivity, improved bioactivity, and reduced toxicity that might lead to the effective delivery of therapeutic agents. High-performance simulation techniques by shedding more light on the dynamical behaviour of neural networks and pathomechanisms of CNS disorders may provide imminent breakthroughs in nanomedicine. In the present review, the importance of integration of nanotechnology-based approaches with computational techniques for targeted delivery of theranostics to the CNS has been highlighted.

Nerve growth factor-carbon nanotube complex exerts prolonged protective effects in an in vitro model of ischemic stroke.

AIMS: The therapeutic potential of nerve growth factor (NGF) against the neurological disorders may be negatively affected by its short half-life. Based on the superior properties of carbon nanotubes (CNTs) for controlled drug delivery, we aimed to prepare CNT-NGF complex and evaluate its effect in an in vitro model of ischemic stroke. MATERIALS AND METHODS: Multi-walled CNTs (MWCNTs)-NGF complex was prepared using amino-functionalized COOH-MWCNTs and characterized by Fourier transform infrared spectroscopy and transmission electron microscopy. PC12 cells in the absence or presence of NGF (0.5, 1, 2µg/ml), acid- or amine-modified MWCNTs, or MWCNTs-NGF complex (2, 4, 8µg/ml) were exposed to 1 and 6h oxygen-glucose deprivation (OGD) followed by 24h re-oxygenation. Cytotoxicity and oxidative stress were evaluated. KEY FINDINGS: OGD significantly reduced the cell viability (P<0.001). NGF dose-dependently increased the cell viability only after 1-h OGD (P<0.05), while, MWCNTs-NGF complex was effective at both 1- and 6-h OGD (P<0.05, P<0.001). NGF reduced the formation of condensed nuclei due to 1-h OGD (P<0.01, P<0.001), while, MWCNTs-NGF showed efficiency at both time points (P<0.05, P<0.01, P<0.001). OGD significantly increased malondialdehyde (MDA) content and decreased catalase (CAT) and superoxide dismutase (SOD) activities (P<0.001). After 1-h OGD, NGF reduced MDA (P<0.001) and increased CAT (P<0.05, P<0.01) and SOD (P<0.01), while, MWCNTs-NGF was effective after both 1- and 6-h OGD (MDA: P<0.01, P<0.001, CAT: P<0.001, SOD: P<0.01, P<0.001). SIGNIFICANCE: Aminated MWCNTs-NGF complex by providing longer lasting effects for NGF might be of therapeutic significance against the disorders associated with NGF deficiency.

Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment in the kindling model of epilepsy.

AIMS: Some conventional antiepileptic drugs induce oxidative stress and cognitive impairment which may limit their clinical applications. Ferulic acid is a phenolic phytochemical with antioxidant and neuroprotective properties that prompted us to evaluate its therapeutic potential in epilepsy which is usually associated with oxidative stress and cognitive decline. MATERIALS AND METHODS: Male Wistar rats received 30mg/kg of pentylenetetrazole (PTZ) intraperitoneally (i.p.) once every alternate day until the development of kindling. The locomotor activity, elevated plus maze, and passive avoidance tests were performed. Oxidative stress was evaluated by the determination of brain malondialdehyde and reduced glutathione. The effects of pre-treatment with ferulic acid (25, 50, 75, and 100mg/kg, i.p.) against PTZ-kindled seizures, cognitive impairment, and oxidative stress were investigated. KEY FINDINGS: Kindling was developed 34.18±1.54days after PTZ treatment which was associated with generalized tonic-clonic seizures (GTCS), myoclonic jerks, cognitive deficit, and oxidative stress. Ferulic acid at doses of 75 and 100mg/kg significantly reduced the seizure score, number of myoclonic jerks, cognitive decline and oxidative stress. Spontaneous locomotor activity did not significantly differ between the groups. SIGNIFICANCE: Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment induced by PTZ kindling. Therefore, this phenolic phytochemical appears as a promising adjuvant for antiepileptic drugs. Meanwhile, further experimental and clinical studies are required to provide insights into the cellular/molecular mechanism(s) underlying the action of ferulic acid.

Application of carbon nanotubes as the carriers of the cannabinoid, 2-arachidonoylglycerol: Towards a novel treatment strategy in colitis.

AIMS: Treatment of colitis has remained a major clinical challenge. The cannabinoid, 2-arachidonoyglycerol (2-AG), has shown beneficial effects in colitis, however, poor solubility or rapid hydrolysis may limit its efficiency. According to the high biocompatibility of carbon nanotubes (CNTs) and their ability for controlled drug delivery, we aimed to prepare multi-walled CNTs-2-AG (MWCNTs-2-AG) complex in order to improve the pharmacological profile of 2-AG and evaluate the therapeutic potential of this nanocomplex in a rat model of colitis. MATERIALS AND METHODS: Aminated MWCNTs-2-AG complex was prepared using acidified MWCNTs and then characterized by Fourier transform infrared spectroscopy and transmission electron microscopy. In vitro cytotoxicity of MWCNTs was evaluated. Colitis was induced by colonic instillation of trinitrobenzene sulfonic acid (TNBS) and the effects of 2-AG solution and various types of MWCNTs on the colonic tissue damage, inflammation, and oxidative stress were evaluated. KEY FINDINGS: Aminated MWCNTs and MWCNTs-2-AG complex exhibited significantly lower cytotoxicity than acidified MWCNTs. Once daily intrarectal application of MWCNTs-2-AG complex (containing 2mg/kg of 2-AG) 2days before and 8days after the induction of colitis effectively reduced the macroscopic and microscopic injuries, malondialdehyde, tumour necrosis factor-α, and interlukin-1ß concentrations, and myeloperoxidase activity. While, free 2-AG (2mg/kg), and acidified or aminated MWCNTs showed no beneficial effects. SIGNIFICANCE: Amino-functionalized MWCNTs appear as the suitable carriers for 2-AG which provide a sustained concentration for this cannabinoid leading to the promising therapeutic effects in the experimental colitis.