Magnetic hybrid nanovesicles for the precise diagnosis and treatment of central nervous system disorders.

INTRODUCTION: Central nervous system (CNS)-related disorders are increasingly being recognized as a global health challenge worldwide. There are significant challenges for effective diagnosis and treatment due to the presence of the CNS barriers which impede the management of neurological diseases. Combination of nanovesicles (NVs) and magnetic nanoparticles (MNPs), referred to as magnetic nanovesicles (MNVs), is now well suggested as a potential theranostic option for improving the management of neurological disorders with increased targeting efficiency and minimized side effects. AREAS COVERED: This review provides a summary of major CNS disorders and the physical barriers limiting the access of imaging/therapeutic agents to the CNS environment. A special focus on the unique features of MNPs and NV is discussed which make them attractive candidates for neuro-nanomedicine. Furthermore, a deeper understanding of MNVs as a promising combined strategy for diagnostic and/or therapeutic purposes in neurological disorders is provided. EXPERT OPINION: The multifunctionality of MNVs offers the ability to overcome the CNS barriers and can be used to monitor the effectiveness of treatment. The insights provided will guide future research toward better outcomes and facilitate the development of next-generation, innovative treatments for CNS disorders.

Nanoparticle-based delivery platforms for the enhanced oral delivery of peptides/proteins.

Biopharmaceutical products are currently well-established in nearly all branches of medicine and are believed to have great potential for the treatment of a broad spectrum of diseases. Peptide/protein drugs exhibit a predominant class of new biopharmaceuticals coming on the market in recent years. Oral delivery of peptides/proteins as a non-invasive therapeutic technique has become an appealing alternative to the parenteral route. However, the efficient oral delivery of peptides/proteins is limited because of their high molecular weight, poor stability and low biodistribution. Nanoparticles (NPs) have shown excellent results in peptide/protein delivery research. In this paper, the use of NPs as delivery systems for peptides/proteins and their ability to be efficiently delivered via the oral route have been described.

Medicines made from peptides and proteins have become important for treating various diseases. One challenge is delivering them effectively through the mouth, as they can be fragile and may not distribute well in the body. Scientists have been studying the use of tiny particles called nanoparticles (NPs) to help solve these problems. In this article, we explore how NPs can enhance the delivery of peptide/protein medicines when taken orally. By using NPs as delivery platforms, these medicines can be protected and absorbed more efficiently, leading to better treatment outcomes.

Nanoparticle Formulations of Antioxidants for the Management of Oxidative Stress in Stroke: A Review.

Stroke is currently one of the primary causes of morbidity and mortality worldwide. Unfortunately, there has been a lack of effective stroke treatment. Therefore, novel treatment strategies are needed to decrease stroke-induced morbidity and promote the patient's quality of life. Reactive oxygen species (ROS) have been recognized as one of the major causes of brain injury after ischemic stroke. Antioxidant therapy seems to be an effective treatment in the management of oxidative stress relevant to inflammatory disorders like stroke. However, the in vivo efficacy of traditional anti-oxidative substances is greatly limited due to their non-specific distribution and poor localization in the disease region. In recent years, antioxidant nanoparticles (NPs) have demonstrated a clinical breakthrough for stroke treatment. Some NPs have intrinsic antioxidant properties and act as antioxidants to scavenge ROS. Moreover, NPs provide protection to the antioxidant agents/enzymes while effectively delivering them into unreachable areas like the brain. Because of their nanoscale dimensions, NPs are able to efficiently pass through the BBB, and easily reach the damaged site. Here, we discuss the challenges, recent advances, and perspectives of antioxidant NPs in stroke treatment.

Nano-Catechin Gel as a Sustained Release Antimicrobial Agent against Clinically Isolated Porphyromonas gingivalis for Promising Treatment of Periodontal Diseases.

During the last two decades, new drug delivery strategies have been invented that have been able to solve microbial resistance against antibiotics. The goal of the current report was to assess the antimicrobial effects of nano-catechin gels against clinically isolated Porphyromonas gingivalis, one of the main causes of periodontal disease. Catechin-loaded chitosan nanoparticles were prepared by adding a catechin solution to a chitosan solution. Then, the mean particle size and the mean surface charge (zeta potential) of the nanoparticles were detected through photon correlation spectroscopy and zeta sizer, respectively. Nano-catechin gels (1000, 500, 250, 125, 62.5, and 31.2 µg/mL) were prepared, and the antimicrobial assay was performed against clinically isolated Porphyromonas gingivalis (P. gingivalis). The clinically obtained P. gingivalis isolates were obtained from periodontitis patients (N = 15). The consequences are specified as descriptive indices. The normality of data was detected by the Shapiro-Wilk test. Then, to compare the data between groups (with a p value < 0.05 as the significance level), SPSS software (version 22) was used via a Mann-Whitney U test. The results showed a nanometer particle size range and a positive zeta potential for the prepared nanoparticles. All the concentrations (1000, 500, 250, 125, 62.5, and 31.2 µg/mL) of nano-catechin gels showed sustained release patterns and were non-toxic against dental pulp stem cells as well. There were no significant differences between the minimal inhibitory concentrations (MICs) for nano-catechin gel (test group) and Chlorhexidine (control group) against 15 isolates (p > 0.05). Then, two groups showed similar antimicrobial effects. The similar antimicrobial activity of catechin nanoparticles and Chlorhexidine, as a potent antimicrobial agents, against clinically isolated P. gingivalis showed that catechin nanoparticles can be used as a potent antimicrobial material for the treatment of periodontal diseases in the near future.

Nanocurcumin Release from Self-Cured Acrylic Resins; Effects on Antimicrobial Action and Flexural Strength.

The placement of orthodontic appliances into the oral area can lead to infection, inflammatory and gingival collapse. Using an antimicrobial and anti-inflammatory material in the matrix of orthodontic appliance may help to reduce these issues. This study aimed to assess the release pattern, the antimicrobial action and the flexural strength of self-cured acrylic resins after adding different weight percentages of curcumin nanoparticles (nanocurcumin). In this in-vitro study, 60 acrylic resin samples were divided into five groups (n = 12) based on the weight percentage of curcumin nanoparticles added to the acrylic powder (0 for control, 0.5, 1, 2.5, and 5%). Then, the dissolution apparatus was used for the release assessment of nanocurcumin form the resins. For antimicrobial action assessment, the disk diffusion method was used and a three-point bending test was performed with a speed of 5 mm/min to determine the flexural strength. Data were analyzed using one-way analysis of variance (ANOVA) and Post-Hoc Tukey tests (with p < 0.05 as significant level). The microscopic images showed the homogeny distribution of nanocuricumin in self-cured acrylic resins in varied concentrations. The release pattern showed a two-step release pattern for all concentrations of nanocurcumin. The one-way ANOVA outcomes indicated that adding curcumin nanoparticles to self-cured resin increased the diameter of the inhibition zones for the groups against Streptococcus mutans (S. mutans) significantly (p < 0.0001). Additionally, as the weight percentage of curcumin nanoparticles increased, the flexural strength decreased (p < 0.0001). However, all strength values were higher than the standard value (50 MPa). No significant difference was detected between the control group and the group with 0.5 percent (p = 0.57). Considering the proper release pattern and the potent antimicrobial activity of curcumin nanoparticles, then the preparing self-cured resins containing curcumin nanoparticles can be beneficial for antimicrobial aims without damaging the flexural strength to use in orthodontic removable applications.

Gelatin-Curcumin Nanocomposites as a Coating for Implant Healing Abutment: In Vitro Stability Investigation.

Regarding the importance of preventing peri-implantitis in dental implants, the current study aimed to coat a healing abutment with gelatin−curcumin nanocomposites, and the stability of this coating on the healing abutment was evaluated. A cell viability measuring test was used to determine the cytotoxicity of nanocomposites against dental pulp stem cells. To show the pattern of curcumin release from nanocomposites, drug dissolution apparatus two was applied. Then, 16 healing abutments were examined in vitro. Titanium healing abutments were coated with the gelatin−curcumin nanocomposite. The dip coating method was applied for coating and the consistency of coated cases was evaluated at intervals of one, 30, and 60 days after coating inside the simulated body fluid (SBF) solution. A scanning electron microscope (SEM) was used for investigating the microstructure and morphology of coatings, and an energy dispersive X-ray (EDX) was applied for determining the combination of the coating. Moreover, the healings were weighed before and after coating via an accurate digital scale with an accuracy of 0.0001. Finally, the data were analyzed using SPSS software. The prepared nanocomposite was non-cytotoxic against tested cells. The nanocomposite showed a relatively rapid release pattern in the first 10 days for curcumin. The release of curcumin from the nanoparticles continued slowly until the 30th day. The weight changes were statistically significant (p-value < 0.001) during this time. Based on the post hoc test, the weight between two times immediately after coating and 30 days after coating, and also one day after coating and 30 days after coating, was statistically insignificant. The results revealed that the coating of the gelatin−curcumin nanocomposite on the healing was successful and this consistency was kept for at least one month. It is necessary to investigate more evaluations in different fields of physicochemical, mechanical, and antimicrobial aspects for coated healing abutments.

Nanoparticle and Stem Cell Combination Therapy for the Management of Stroke.

Stroke is currently one of the primary causes of morbidity and mortality worldwide. Unfortunately, the available treatments for stroke are still extremely limited. Indeed, stem cell (SC) therapy is a new option for the treatment of stroke that could significantly expand the therapeutic time window of stroke. Some proposed mechanisms for stroke-based SC therapy are the incorporation of SCs into the host brain to replace dead or damaged cells/tissues. Moreover, acute cell delivery can inhibit apoptosis and decrease lesion size, providing immunomudolatory and neuroprotection effects. However, several major SC problems related to SCs such as homing, viability, uncontrolled differentiation, and possible immune response, have limited SC therapy. A combination of SC therapy with nanoparticles (NPs) can be a solution to address these challenges. NPs have received considerable attention in regulating and controlling the behavior of SCs because of their unique physicochemical properties. By reviewing the pathophysiology of stroke and the therapeutic benefits of SCs and NPs, we hypothesize that combined therapy will offer a promising future in the field of stroke management. In this work, we discuss recent literature in SC research combined with NP-based strategies that may have a synergistic outcome after stroke incidence.

The Antimicrobial and Anti-Biofilm Effects of Hypericum perforatum Oil on Common Pathogens of Periodontitis: An In Vitro Study.

The antibacterial and anti-biofilm effects of Hypericum perforatum oil against the common pathogens of periodontitis (Escherichia coli, Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, Porphyromonas gingivalis) was investigated. Disk diffusion (DD), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) approaches were applied to test the antimicrobial effects. In order to determine the anti-biofilm effects, the amount of bacterial biofilm formation was assessed using the microtiter plate technique. The anti-biofilm effects were then confirmed by determining the minimum biofilm inhibitor concentration (MBIC). The MIC, MBC, MBIC, and DD values were 64, 256, 512 µg/mL, and 14 mm for Staphylococcus aureus; 128, 256, 512 µg/mL, and 16 mm for Streptococcus mutans; 256, 512, 256 µg/mL, and 20 mm for Escherichia coli; 32, 128, 512 µg/mL, and 16 mm for Enterococcus faecalis; and 64, 128, 256 µg/mL, and 15 mm for Porphyromonas gingivalis, respectively. According to our results, Hypericum perforatum oil has antibacterial and anti-biofilm properties against the common bacteria associated with periodontitis.

The Link between Stroke Risk and Orodental Status-A Comprehensive Review.

One of the primary causes of disability and mortality in the adult population worldwide is stroke. A person's general health is significantly impacted by their oral and dental health. People who have poor oral health are more susceptible to conditions such as stroke. Stroke risk has long been linked to oral and dental conditions. The risk of stroke and its cost impact on the healthcare systems appear to be significantly reduced as a result of the decline in the incidence and prevalence of oral and dental illnesses. Hypothetically, better management of oral hygiene and dental health lead to reduced stroke risk. To the authors' best knowledge, for the first time, the potential link between dental health and stroke were cross-examined. The most typical stroke symptoms, oral and dental illnesses linked to stroke, and the role of oral healthcare professionals in stroke prevention are revealed. The potential mediating processes and subsequent long-term cognitive and functional neurological outcomes are based on the available literature. It must be noted that periodontal diseases and tooth loss are two common oral health measures. Lack of knowledge on the effects of poor oral health on systemic health together with limited access to primary medical or dental care are considered to be partially responsible for the elevated risk of stroke. Concrete evidence confirming the associations between oral inflammatory conditions and stroke in large cohort prospective studies, stratifying association between oral disease severity and stroke risk and disease effects on stroke survival will be desirable. In terms of clinical pathology, a predictive model of stroke as a function of oral health status, and biomarkers of systemic inflammation could be useful for both cardiologists and dentists.

Salivary biomarkers in cancer.

In recent years, the comprehensive analysis of saliva, i.e., salivaomics, has played an increasing role in biomarker discovery for disease detection in general and cancer specifically. Saliva is a readily accessible, non-invasive and low-cost specimen that can be used to detect biomarkers of clinical relevance. Saliva-based "omics" technologies, which include proteomics, transcriptomics, metabolomics and microbiomics, have rapidly evolved and may be applicable in point-of-care detection, liquid biopsy and nanoscience. Advances in analytical methods has increased the scope and application of salivaomics from solely the oral cavity to the entire physiologic system, and accordingly to personalized medicine. In this chapter, we highlight recent advances in analytical approaches to identify and detect biomarkers in saliva and their potential use as diagnostic, prognostic and therapeutic markers with a focus on cancer.

Application of Nano-based Drug Loading Systems in the Treatment of Neurological Infections: An Updated Review.

Infection of the central nervous system (CNS) is a global healthcare concern with high rates of death and disease. CNS infections mainly include meningitis, encephalitis, and brain abscesses. Bacteria, viruses, fungi, protozoa, and parasites are the most common causes of neuroinfections. There are many types of medications used in the treatment of CNS infections, but drug delivery through the blood-brain barrier (BBB) is a major challenge to overcome. The BBB is a specialized multicellular barrier separating the neural tissue from the peripheral blood circulation. Unique characteristics of the BBB allow it to tightly control the movement of ions and molecules. Thus, there is a critical need to deal with these conditions with the aim of improving novel antimicrobial agents. Researchers are still struggling to find effective drugs to treat CNS infections. Nanoparticle (NP)-mediated drug delivery has been considered a profound substitute to solve this problem because NPs can be tailored to facilitate drug transport across the BBB. NPs are colloidal systems with a size range of 1-1000 nm, which can be used to encapsulate therapeutics, improve drug transport across the BBB, and target specific brain areas in CNS infections. A wide variety of NPs has been displayed for the CNS delivery of therapeutics, especially when their surfaces are coated with targeting moieties. This study aimed to review the available literature on the application of NPs in CNS infections.

The Therapeutic Benefits of Intravenously Administrated Nanoparticles in Stroke and Age-related Neurodegenerative Diseases.

The mean global lifetime risk of neurological disorders such as stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) has shown a large effect on economy and society. Researchers are still struggling to find effective drugs to treat neurological disorders and drug delivery through the blood-brain barrier (BBB) is a major challenge to be overcome. The BBB is a specialized multicellular barrier between peripheral blood circulation and neural tissue. Unique and selective features of the BBB allow it to tightly control brain homeostasis as well as the movement of ions and molecules. Failure in maintaining any of these substances causes BBB breakdown and subsequently enhances neuroinflammation and neurodegeneration. BBB disruption is evident in many neurological conditions. Nevertheless, the majority of currently available therapies have tremendous problems with drug delivery into the impaired brain. Nanoparticle (NP)-mediated drug delivery has been considered a profound substitute to solve this problem. NPs are colloidal systems with a size range of 1-1000 nm which can encapsulate therapeutic payloads, improve drug passage across the BBB, and target specific brain areas in neurodegenerative/ischemic diseases. A wide variety of NPs has been displayed for the efficient brain delivery of therapeutics via intravenous administration, especially when their surfaces are coated with targeting moieties. Here, we discuss recent advances in the development of NP-based therapeutics for the treatment of stroke, PD, and AD, as well as the factors affecting their efficacy after systemic administration.

Antimicrobial Benefits of Flavonoids and their Nanoformulations.

Nowadays, there is an urgent need to discover and develop long-term and effective antimicrobial and biofilm-inhibiting compounds. Employing combination therapies using novel drug delivery systems and also natural antimicrobial substances is a promising strategy in this field. Nanoparticles (NPs)-based materials have become well appreciated in recent times due to their function as antimicrobial agents or carriers for promoting the bioavailability and effectiveness of antibiotics. Flavonoids belong to the promising groups of bioactive compounds abundantly found in fruits, vegetables, spices, and medicinal plants with strong antimicrobial features. Flavonoids and NPs have the potential to work as alternatives to the conventional antimicrobial agents, when used alone as well as in combination. Different classes of flavonoid NPs may be particularly advantageous in treating microbial infections. The most important antimicrobial mechanisms of flavonoid NPs include oxidative stress induction, non-oxidative mechanisms, and metal ion release. However, the efficacy of flavonoid NPs against pathogens and drug-resistant pathogens changes according to their physicochemical characteristics as well as the particular structure of microbial cell wall and enzymatic composition. In this review, we provide an outlook on the antimicrobial mechanism of flavonoid-based NPs and the crucial factors involved in it.

Targeting Multidrug Resistance With Antimicrobial Peptide-Decorated Nanoparticles and Polymers.

As a category of small peptides frequently found in nature, antimicrobial peptides (AMPs) constitute a major part of the innate immune system of various organisms. Antimicrobial peptides feature various inhibitory effects against fungi, bacteria, viruses, and parasites. Due to the increasing concerns of antibiotic resistance among microorganisms, development of antimicrobial peptides is an emerging tool as a favorable applicability prospect in food, medicine, aquaculture, animal husbandry, and agriculture. This review presents the latest research progress made in the field of antimicrobial peptides, such as their mechanism of action, classification, application status, design techniques, and a review on decoration of nanoparticles and polymers with AMPs that are used in treating multidrug resistance. Lastly, we will highlight recent progress in antiviral peptides to treat emerging viral diseases (e.g., anti-coronavirus peptides) and discuss the outlook of AMP applications.

Safety issues of nanomaterials for dermal pharmaceutical products.

Nanomaterials (NMs) have favorable application in the medicine area, specifically in regard to the carry of pharmaceutical ingredients to provide targeted drug delivery systems. The skin is an excellent route for the delivery of pharmaceutical nano-transporters for skin-related applications. The physicochemical properties of nanomaterials such as size, hydrophobicity, loading capacity, charge and weight are vital for a skin penetrating system. Many nanocarriers such as polymeric nanoparticles, inorganic nanomaterials and, lipid nanostructures have been utilized for dermal delivery of active ingredients and others such as carbon nanotubes and fullerenes require more examination for future application in the skin-related area. Some negative side effects and nano-cytotoxicity of nanomaterials require special attention while investigating different nanomaterials for medicinal applications. Then, in the current review, we had a view on the safety issues of nanomaterials for dermal pharmaceutical products.

Development and characterization of bilayered tablets of diazepam for oral drug delivery: design, optimization and in vitro evaluation.

Aims: The oral bioavailability of drugs can be limited by their short residence time in the gastrointestinal tract. This study was performed to design bilayered floating tablets of diazepam comprising immediate-release and controlled-release layers. Methods: The tablets were prepared using sodium starch glycolate, polyvinyl pyrrolidone, hydroxypropyl methylcellulose and microcrystalline cellulose and evaluated for their characteristics. Results: The optimized formulation was found to be buoyant for 8 h on simulated gastric fluid. Hydroxypropyl methylcellulose K4M and microcrystalline cellulose sustained the release of diazepam from the controlled-release layer. The optimized formulation exhibited an extended release period of 8 h. Discussion/conclusion: It can be concluded that bilayered tablets of diazepam may extend the residence time of the drug at the site of absorption.

Development and characterization of a novel mucoadhesive sol-gel suppository of sumatriptan: design, optimization, in vitro and ex vivo evaluation for rectal drug delivery.

Aim: Sumatriptan (ST) is used for the treatment of migraine and cluster headaches. However, it exhibits low oral bioavailability (15%) due to the high first-pass metabolism. The aim of this work was to formulate an ST rectal hydrogel. Methods: Hydrogels were formulated according to a Box-Behnken design using pluronic F-127 (PF-127) and chitosan as thermogelling and mucoadhesive agents, respectively. The rectal permeability was examined using a sheep rectal mucosa. Results: Among all the formulations, the hydrogel S2 showed satisfactory drug content (4.50%), gelling temperature (32°C), pH (6.41), viscosity (105 cP) and strength (15.90 sec). Mucoadhesive strength was adequate to provide a prolonged residence time. The flux of hydrogel S2 was calculated to be 0.0003 µg/cm2.min. Conclusion: The ST hydrogel can provide a potential opportunity to overcome the first pass metabolism and reduce drug dose.

Portland Cement: An Overview as a Root Repair Material.

Portland cement (PC) is used in challenging endodontic situations in which preserving the health and functionality of pulp tissue is of considerable importance. PC forms the main component of mineral trioxide aggregate (MTA) and demonstrates similar desirable properties as an orthograde or retrograde filling material. PC is able to protect pulp against bacterial infiltration, induce reparative dentinogenesis, and form dentin bridge during the pulp healing process. The biocompatibility, bioactivity, and physical properties of PC have been investigated in vitro and in animal models, as well as in some limited clinical trials. This paper reviews Portland cement's structure and its characteristics and reaction in various environments and eventually accentuates the present concerns with this material. This bioactive endodontic cement has shown promising success rates compared to MTA; however, considerable modifications are required in order to improve its characteristics and expand its application scope as a root repair material. Hence, the extensive chemical modifications incorporated into PC composition to facilitate preparation and handling procedures are discussed. It is still important to further address the applicability, reliability, and cost-effectiveness of PC before transferring into day-to-day clinical practice.

The Factors Determining the Skin Penetration and Cellular Uptake of Nanocarriers: New Hope for Clinical Development.

The skin provides a protective barrier against toxic environments and also offers a valuable route for topical drug delivery. The stratum corneum (SC) is the outermost layer of the skin and serves as the major barrier to chemical transfer through the skin. The human skin barrier is particularly difficult to overcome because of the complex composition and structure of the SC. Nanoparticulate carriers have gained widespread attention in topical drug delivery due to their tunable and versatile properties. The present review summarizes the main factors involved in skin penetration of nanocarriers containing the drug. Employment of nanotechnology in topical delivery has grown progressively during recent years; however, it is important to monitor the skin penetration of nanocarriers prior to their use to avoid possible toxic effects. Nanocarriers can act as a means to increase skin permeation of drugs by supporting direct interaction with the SC and increasing the period of permanence on the skin. Skin penetration is influenced by the physicochemical characteristics of nanocarriers such as composition, size, shape, surface chemistry, as well as skin features. Considering that the target of topical systems based on nanocarriers is the penetration of therapeutic agents in the skin layers, so a detailed understanding of the factors influencing skin permeability of nanocarriers is essential for safe and efficient therapeutic applications.

Safety and Toxicity Issues of Therapeutically Used Nanoparticles from the Oral Route.

The emerging science of nanotechnology sparked a research attention in its potential benefits in comparison to the conventional materials used. Oral products prepared via nanoparticles (NPs) have garnered great interest worldwide. They are used commonly to incorporate nutrients and provide antimicrobial activity. Formulation into NPs can offer opportunities for targeted drug delivery, improve drug stability in the harsh environment of the gastrointestinal (GI) tract, increase drug solubility and bioavailability, and provide sustained release in the GI tract. However, some issues like the management of toxicity and safe handling of NPs are still debated and should be well concerned before their application in oral preparations. This article will help the reader to understand safety issues of NPs in oral drug delivery and provides some recommendations to the use of NPs in the drug industry.