Nanomaterials in biology and medicine: a new perspective on its toxicity and applications.

Nanotechnology offers excellent prospects for application in biology and medicine. It is used for detecting biological molecules, imaging, and as therapeutic agents. Due to nano-size (1-100 nm) and high surface-to-volume ratio, nanomaterials possess highly specific and distinct characteristics in the biological environment. Recently, the use of nanomaterials as sensors, theranostic, and drug delivery agents has become popular. The safety of these materials is being questioned because of their biological toxicity, such as inflammatory responses, cardiotoxicity, cytotoxicity, inhalation problems, etc., which can have a negative impact on the environment. This review paper focuses primarily on the toxicological effects of nanomaterials along with the mechanisms involved in cell interactions and the generation of reactive oxygen species by nanoparticles, which is the fundamental source of nanotoxicity. We also emphasize the greener synthesis of nanomaterials in biomedicine, as it is non-hazardous, feasible, and economical. The review articles shed light on the complexities of nanotoxicology in biosystems and the environment.

Corrigendum: Modulation of immune response by nanoparticle-based immunotherapy against food allergens.

[This corrects the article DOI: 10.3389/fimmu.2023.1229667.].

Modulation of immune response by nanoparticle-based immunotherapy against food allergens.

The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only symptomatic relief. Great strides have been made in research and in clinics in recent years to offer novel therapies for the treatment of allergic disorders. However, current allergen immunotherapy has its own shortcomings in terms of long-term efficacy and safety, due to the local side effects and the possibility of anaphylaxis. Allergen-specific immunotherapy is an established therapy in treating allergic asthma, allergic rhinitis, and allergic conjunctivitis. It acts through the downregulation of T cell, and IgE-mediated reactions, as well as desensitization, a process of food tolerance without any allergic events. This would result in a protective reaction that lasts for approximately 3 years, even after the withdrawal of therapy. Furthermore, allergen-specific immunotherapy also exploits several routes such as oral, sublingual, and epicutaneous immunotherapy. As the safety and efficacy of allergen immunotherapy are still under research, the exploration of newer routes such as intra-lymphatic immunotherapy would address unfulfilled needs. In addition, the existence of nanoparticles can be exploited immensely in allergen immunotherapy, which would lead to safer and efficacious therapy. This manuscript highlights a novel drug delivery method for allergen-specific immunotherapy that involves the administration of specific allergens to the patients in gradual increasing doses, to induce desensitization and tolerance, as well as emphasizing different routes of administration, mechanism, and the application of nanoparticles in allergen-specific immunotherapy.

Liposomal drug delivery to the lungs: a post covid-19 scenario.

High local delivery of anti-infectives to the lungs is required for activity against infections of the lungs. The present pandemic has highlighted the potential of pulmonary delivery of anti-infective agents as a viable option for infections like Covid-19, which specifically causes lung infections and mortality. To prevent infections of such type and scale in the future, target-specific delivery of drugs to the pulmonary region is a high-priority area in the field of drug delivery. The suboptimal effect of oral delivery of anti-infective drugs to the lungs due to the poor biopharmaceutical property of the drugs makes this delivery route very promising for respiratory infections. Liposomes have been used as an effective delivery system for drugs due to their biocompatible and biodegradable nature, which can be used effectively for target-specific drug delivery to the lungs. In the present review, we focus on the use of liposomal drug delivery of anti-infectives for the acute management of respiratory infections in the wake of Covid-19 infection.

Deducing the Interplay Between Gut Flora and Respiratory Diseases: A New Therapeutic Strategy?

The gastrointestinal system, also referred to as the gut, is a universe that colonizes trillions of microbes. In addition to its digestive functions, the gut represents a biosystem that determines all the health vectors. It is now recognized as one of the body's defense systems, and good gut health regulates the body's immune responses. Disturbance of this barrier can trigger many diseases, including respiratory tract infections, as there is a close correlation between the gut microbiome and the chances of triggering illness. This review investigates the various factors affecting the gut microbiome, the diseases that can result from the dysregulation of the same, and their molecular mechanisms. The most basic solution to tackle this problem is to maintain the gut microbiome at the desired level. Timely diagnosis and interventions are needed for the proper management of the ensuing conditions. It is important to address the effects of factors on the gut microbiome and thereby regulate this level. The study also found that dysregulation in the system can lead to various diseases such as asthma, COPD, lung cancer following their respective pathways. In short, this paper reinforces the importance of the gut microbiome, the need to maintain its average level, and the need for proper interventions to treat the consequences. The manuscript posit that medications, diet as well and good physiological conditions of the human body can alter the microbiome and can ward off respiratory infections.

Development of a Novel Methotrexate-Loaded Nanoemulsion for Rheumatoid Arthritis Treatment with Site-Specific Targeting Subcutaneous Delivery.

Rheumatoid arthritis (RA) is a systemic, chronic autoimmune disease that causes disability due to progressive inflammation and destruction of the tissues around the joints. Methotrexate is mainly used to prevent the progression of joint destruction and reduce the deformity. The major challenge in treating RA with methotrexate is the systemic side effects that limit dose escalation. Hence, a novel formulation of a methotrexate-loaded nanoemulsion for subcutaneous administration was developed that aims to deliver methotrexate into the system via the lymph. The methotrexate-loaded nanoemulsion was prepared by using the aqueous-titration method. The prepared nanoemulsion was investigated for particle size, surface charge, surface morphology, entrapment efficiency, DSC (differential scanning colorimetry), drug release, hemocompatibility assay, and cytotoxicity, as well as anti-arthritic and stability studies. The vesicle size, zeta potential, PDI (polydispersity index), and entrapment efficiency of the optimized nanoemulsion were 87.89 ± 2.86 nm, 35.9 ± 0.73 mV, 0.27, and 87 ± 0.25%, respectively. The DSC study showed that the crystalline methotrexate was converted to an amorphous form and the drug was fully incorporated into the vesicles. After 72 h, the optimized nanoemulsion showed a drug release of 96.77 ± 0.63%, indicating a sustained-release dosage form. Cytocompatibility testing by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay on macrophage cell lines showed that the nanoemulsion was non-toxic. The formulation showed significant anti-arthritic activity compared to the marketed drug solution. In addition, the nanoemulsion containing methotrexate remained stable for three months when stored at a low temperature. Since the nanoemulsion containing methotrexate has excellent physicochemical properties and lowers systemic side effects by targeted delivery, it is a desirable technology for subcutaneous drug delivery.

Formulation and in-vitro characterization of fast-disintegrating herbal extract sublingual immunotherapy tablet for peanut-induced allergic asthma.

Background: Allergen immunotherapy (AIT) involves the regimen of gradually incrementing doses of the allergen, thereby inducing desensitization and tolerance. Sublingual Immunotherapy tablets (SLIT-tablets) have been formulated for several allergies and had manifested efficacy for allergic rhinitis and allergic asthma. SLIT promises an alternative method to other routes of AIT enabling patients to self-administer AIT. Objective: The study aimed to formulate fast disintegrating SLIT containing crude peanut extract for peanut-induced allergic asthma. Methods: The crude peanut extract was prepared by a simple extraction method and was subjected to quantitative and qualitative analysis. The extract was also characterised for its physical properties. The preformulation study for the extract and excipients of the tablet was performed using FT-IR spectroscopy and Differential scanning calorimetry. The tablet powder blends were characterised for pre-compression properties. The SLIT tablets were developed by direct compression and the post-compression evaluation was performed. Results: The results of the quantitative and qualitative analysis of extract confirmed the presence of peanut proteins in the extract. The preformulation studies using FT-IR spectroscopy and Differential Scanning Calorimetry revealed that there is no significant interaction between the CPE and excipients. The pre-compression characterisation showed that the powder blends had good flowproperties. Three doses of SLIT tablets were formulated with each dose containing four batches and the tablet of each dose was optimized by studying the effect of varying concentrations of super disintegrants on disintegration time and dissolution rate. The post compression characterization of the tablets was performed and the optimized batch of the three doses with the concentration of 5% crospovidone and 2% croscarmellose sodium showed less wetting time and high-water absorption ratio, shorter disintegration time of 14secs and maximum drug release of >90% within 2-3 min. Conclusion: The results indicated the suitability of formulated SLIT tablets for peanut induced allergic asthma.

Non alcoholic palm nectar from Cocos nucifera as a promising nutraceutical preparation.

Nonalcoholic Palm Nectar from Cocos nucifera (NPNC), a bio-refresher obtained from the juvenile inflorescence of coconut palm; is prominent as a nutritional health drink. The aim of this study was to investigate the nutritional and medicinal properties of NPNC and its products; sugar (NPNCS) and honey (NPNCH). The collected samples were subjected to physicochemical evaluations such as pH, Titrable Acidity, Total Soluble Solids, and Ash value, using standard techniques. The analysis revealed the suitability of NPNC as a natural health drink over conventionally available beverage. The elemental compositions of the samples were determined by using Inductive Coupled Plasma-Atomic Emission Spectrometry and demonstrated that NPNCH is enriched with iron and NPNCS with calcium. Vitamin C present in the samples was determined by using 2,6-Dichlorophenol indophenol redox titration method. Hydrolysable polyphenols, tannins, and flavonoids are determined by Folin-Ciocalteu, by Folin-Denis's technique and by aluminium chloride colorimetric methods, respectively. In NPNC, the dominance of Vitamin C as antioxidant is observed. Diuretic activity of samples was determined by Lipschitz method, and the results revealed that NPNC exhibited significant diuretic activity, comparable with furosemide. Immunomodulatory activities of the samples were evaluated by using indirect hemagglutination test and by using delayed type hypersensitivity (DTH) response. NPNC, NPNCS, and NPNCH exhibited stimulatory effect on humoral and cell-mediated immunity, which is comparable with that of standard immunomodulator levamizole. Subacute toxicity studies of selected samples were done in Wistar rats and the results proved the boicompatibility of the samples without systemic toxic effects. PRACTICAL APPLICATIONS: The use of commercially available carbonated beverages and energy drinks in young adults are associated with negative health outcomes with increased incidence of diabetes, sleep disturbances, and dental problems. Even though, such complications are there, the energy drink industries have grown dramatically accounting for major percentage of market sale. Researchers are in search for natural health drinks with some medicinal value to avoid the negative impact on consumers' health. Nonalcoholic Palm Nectar from Cocos nucifera (NPNC) is considered as zero alcoholic natural health drink. The focus of this study is to reveal the potential medicinal properties of NPNC and its products; honey (NPNCH) and sugar (NPNCS). If the nutritional and medicinal values of the selected preparations from natural sources can be proved with scientific evidence, its ability to beat commercially available carbonated beverages and energy drinks with negative health consequences may get widespread acceptance.

Enhanced Lymphatic Uptake of Leflunomide Loaded Nanolipid Carrier via Chylomicron Formation for the Treatment of Rheumatoid Arthritis.

Purpose: The current study aims the lymphatic delivery of leflunomide loaded nanostructured lipid carriers (LNLC) for the treatment of rheumatoid arthritis, mainly focussed to enhance the lymphatic delivery via chylomicron formation, improved bioavailability and reduced systemic toxicity. Methods: Melt emulsification ultra-sonication method was used to formulate the nanostructured lipid carrier (NLC) containing leflunomide. Four batches were prepared by using various concentration of surfactants (tween 80 and poloxmer 188) and lipid mixtures (stearic acid and oleic acid). All the formulations were studied for various physiochemical properties Results: The formulation with increased concentration of lipid and surfactants showed highest entrapment efficiency (93.96 ± 0.47%) and better drug release (90.35%) at the end of 48 hrs. In vivo tests were carried out to determine the antiarthritic potential of the formulation in Sprague-dawley rats for a duration of 30d. The effect was evaluated by measuring the reduction in knee thickness. LNLC showed a marked reduction in inflammation compared to standard drug. Intestinal lymphatic uptake studies of LNLC were performed by intraduodenal administration and compared with leflunomide drug solution. The mesenteric lymph node was analysed by HPLC method and the concentration of drug was estimated. It showed that LNLC having highest uptake (40.34µg/ml) when compared with leflunomide drug solution (10.04µg/ml). Radiographic analysis and histopathological studies showed the formation of healthy cartilage after treatment period. Conclusion: The results suggested that LNLC has the potential to reduce the systemic toxicities associated with conventional therapy along with improved efficacy in the treatment of rheumatoid arthritis.

Development of phytovesicles containing triterpenoids from Samadera indica.

INTRODUCTION: Samadera indica belonging to Simaroubaceae family is being used traditionally for many diseases including arthritis, edema, itching, skin diseases, constipation, and general debility. OBJECTIVE: The effectiveness of any drug delivery system depends upon its ability to deliver the active components at therapeutic level. In this study, a novel phyto vesicular formulation for the enhanced topical delivery of methanol extract of S. indica in order to treat skin infections was developed. MATERIALS AND METHODS: The methanol extract fraction of leaves of S. indica which showed more antifungal activity was purified to separate an antifungal compound. Phytovesicles were formulated using the more antifungal fraction in order to treat topical and deep seated fungal infections. Pytovesicles were prepared using 1:2 molar ratio of antifungal triterpenoid from S. indica (AFTSI)-phosphatidylcholine by film hydration method. RESULTS AND DISCUSSION: Chloroform 100% fraction of methanol extract of S. indica showed more activity against the fungus Candida albicans. Further purification gave a fraction with minimum inhibitory concentration value of 15.6 mg/ml against C. albicans and showed positive test for triterpenoids. The fraction was named as AFTSI. A compound (20 mg) was isolated from this fraction at an RF value. The phytovesicle gel formulated using AFTSI showed enhanced skin permeability and antifungal activity. CONCLUSION: The study demonstrated that the phytovesicular gel developed using methanol extract of S. indica would be beneficial for treating deep seated fungal infections.

Pros and cons of phospholipid asymmetry in erythrocytes.

Phospholipids of erythrocyte are found as bilayer with choline containing phospholipid like phosphatidyl choline and sphingomylein in the outer layer and amine containing phospholipid like phosphatidyl ethanolamine and phosphatidyl serine in the inner layer. This arrangement is known as phospholipid asymmetry. Lipid asymmetry is maintained throughout the entire life span of red blood cell and is disturbed when cells enter into the stage of apoptosis. We here discuss some of the conditions in which phospholipid asymmetry of erythrocyte is maintained and disturbed and the various detection methods to check the distortion phospholipid asymmetry of it.

Formulation and optimization of clotrimazole-loaded proniosomal gel using 3(2) factorial design.

The main aim of the study was to develop and statistically optimize the proniosomal gel for enhanced transdermal delivery using 3(2) factorial designs to investigate the influence of both non-ionic surfactant and cholesterol to maximize the entrapment efficiency and flux. The concentration of non-ionic surfactant and cholesterol were taken as independent variables, while entrapment efficiency and flux were taken as dependent variables. The study showed that the entrapment efficiency depends on both cholesterol and surfactant, whereas permeation flux depends only on the surfactant. Proniosomal gel showed a significantly enhanced drug permeation through the skin, with an enhancement ratio 3.81±1.85 when compared to the drug solution. Comparative evaluation of permeation studies and the in vitro release study of optimized proniosomal gel (F5) with that of marketed gel and carbopol gel showed that the penetration of the optimized formulation was enhanced 1.75 times in comparison with that of the marketed formulation, and the release was in a controlled manner. Similarly, the anticandidial activity showed a significantly higher activity (p<0.05) than the marketed and carbopol gel. This may be due to the enhanced penetration of noisome-containing drug through the fungal cell wall, inhibiting the ergo sterol synthesis, thereby causing the fungal cell death due to the presence of penetration enhancer. The stability study at two different temperatures (30 ± 2°C and 4 ± 2°C) confirmed that the formulations were stable even at the end of 45 days. Hence, proniosomal gel is an efficient carrier for the delivery of clotrimazole, thereby prolonging the action.

Development and evaluation of antimicrobial herbal formulations containing the methanolic extract of Samadera indica for skin diseases.

Samadera indica Gaetrn (Simaroubaceae) is claimed to possess various pharmacological activities like antioxidant, antifungal, antitumor, antiviral, and so on, but its taste is bitter. The aim of the present study is to investigate the toxicity of the methanolic extract and to develop suitable herbal formulations of the methanolic extract of Samadera indica, having efficient antimicrobial activity. The methanolic extract prepared from the dried leaves of Samadera indica by continuous hot percolation, were used to examine the toxicity, according to the OECD 423 guidelines, in Swiss Albino mice. Topical formulations were prepared by incorporating Samadera indica (5% w / w) in an emulsifying ointment and a carbopol gel base and evaluated for physical parameters and in-vitro antimicrobial activity (S. aureus, P. aeruginosa and C. albicans). The study reveals that no animals under the study showed any clinical signs of toxicity or mortality when administered a dose of 5 - 2000 mg / kg body weight. Therefore, the maximum tolerated dose of the methanolic extract of Samadera indica was above 2000 mg / kg body weight. The formulated ointment and gel had acceptable physical parameters that showed that they were compatible with the skin, and in addition to this, these formulations passed the short-term stability studies. The in-vitro antimicrobial activity studies showed that the formulated ointment showed significantly strong (p < 0.05) activity against S. aureus, P. aeruginosa and C. albicans than the formulated gel. Thus, the present study concludes that the formulated ointment and gel are safe and efficient antimicrobial formulations for the topical delivery of the methanolic extract of Samadera indica.