In-depth Mechanism, Challenges, and Opportunities of Delivering Therapeutics in Brain Using Intranasal Route.

Central nervous system-related disorders have become a continuing threat to human life and the current statistic indicates an increasing trend of such disorders worldwide. The primary therapeutic challenge, despite the availability of therapies for these disorders, is to sustain the drug's effective concentration in the brain while limiting its accumulation in non-targeted areas. This is attributed to the presence of the blood-brain barrier and first-pass metabolism which limits the transportation of drugs to the brain irrespective of popular and conventional routes of drug administration. Therefore, there is a demand to practice alternative routes for predictable drug delivery using advanced drug delivery carriers to overcome the said obstacles. Recent research attracted attention to intranasal-to-brain drug delivery for promising targeting therapeutics in the brain. This review emphasizes the mechanisms to deliver therapeutics via different pathways for nose-to-brain drug delivery with recent advancements in delivery and formulation aspects. Concurrently, for the benefit of future studies, the difficulties in administering medications by intranasal pathway have also been highlighted.

Nano-nutraceuticals to Combat Oxidative Stress: Unlocking Newer Paradigms in Adjuvant Therapy.

Nutraceuticals are products that provide both nutritional and therapeutic benefits. These compounds can slow the aging process and provide physiological effects shielding individuals from acute and chronic diseases. People's interests have shifted from allopathic to Ayurvedic to nutraceuticals in recent years. These are often common dietary supplements that have drawn customers worldwide because of their high nutritional safety and lack of adverse effects when used for a long time. Although conventional dosage forms, including pills, tablets, and semi-solids, are still available, they nevertheless have poorer bioavailability, less stability, and less effectiveness for targeted delivery of bioactives. The use of effective nanocomplex systems as nano-antioxidants using nanotechnology has become a promising field. Among its many uses, nanotechnology is mostly used to create foods and nutraceuticals that are more bioavailable, less toxic, and more sustainable. Additionally, it has been emphasized how precisely nano-pharmaceuticals for oxidative stress produce the desired effects. These improvements show improved antioxidant delivery to the target region, reduced leakage, and increased targeting precision. The outcomes demonstrated that oxidative stress-related illnesses can be effectively treated by lowering ROS levels with the use of nanonutraceuticals. The major ideas and uses of nano-nutraceuticals for health are outlined in this review, with an emphasis on reducing oxidative stress.

Chimeric hepatitis B surface antigen virus-like particles expressing the strep A epitope p*17 elicit a humoral immune response in mice.

To optimize immunogenicity, bacterial epitopes in putative vaccine constructs can be presented to immune cells as multiple repeated structures on a defined nanoparticle. Virus-like particles (VLPs) are viral capsid proteins that self-assemble to form compact and highly ordered nanoparticles that are within the optimal size range for uptake by dendritic cells. VLPs mimic the live virus in size and form but contain no viral genetic material, are therefore noninfective and are the basis of safe and effective vaccines against hepatitis B virus (HBV) and human papillomavirus (HPV). Due to their particulate nature, molecular stability, and expression of high density and repetitive antigen displays, recombinant cell culture-derived VLPs are ideal platforms for the delivery of small molecules, including bacterial epitopes. We developed a putative vaccine by expressing a minimal epitope from the bacterium Streptococcus pyogenes (Strep A) on the surface of a recombinant VLP comprising multiple copies of HBV small envelope protein (HBsAg-S). Strep A is responsible for a wide spectrum of human infections and postinfectious diseases that disproportionately affect children and young adults living in resource-poor communities. No vaccine is currently available to offer sufficiently broad protection from the numerous and diverse strains of Strep A endemic in these at-risk populations. The Strep A antigen targeted by our vaccine construct is p*17, a cryptic epitope from a highly conserved region of the Strep A M-protein with demonstrated enhanced immunogenicity and broad protective potential against Strep A. To ensure surface expression and optimal immunogenicity, we expressed p*17 within the immunodominant "a" determinant of HBsAg-S. The recombinant VLPs (VLP-p*17) expressed in HEK293T cells spontaneously formed 22 nm particles and induced the production of high titers of p*17-specific IgG in BALB/c mice immunized with three 0.5 µg doses of VLP-p*17 formulated with adjuvant.

Disruption of IL-17-mediated immunosurveillance in the respiratory mucosa results in invasive Streptococcus pyogenes infection.

Introduction: Streptococcus pyogenes is a Gram-positive pathogen that causes a significant global burden of skin pyoderma and pharyngitis. In some cases, infection can lead to severe invasive streptococcal diseases. Previous studies have shown that IL-17 deficiency in mice (IL-17-/-) can reduce S. pyogenes clearance from the mucosal surfaces. However, the effect of IL-17 on the development of severe invasive streptococcal disease has not yet been assessed. Methods: Here, we modeled single or repeated non-lethal intranasal (IN) S. pyogenes M1 strain infections in immunocompetent and IL-17-/- mice to assess bacterial colonization following a final IN or skin challenge. Results: Immunocompetent mice that received a single S. pyogenes infection showed long-lasting immunity to subsequent IN infection, and no bacteria were detected in the lymph nodes or spleens. However, in the absence of IL-17, a single IN infection resulted in dissemination of S. pyogenes to the lymphoid organs, which was accentuated by repeated IN infections. In contrast to what was observed in the respiratory mucosa, skin immunity did not correlate with the systemic levels of IL-17. Instead, it was found to be associated with the activation of germinal center responses and accumulation of neutrophils in the spleen. Discussion: Our results demonstrated that IL-17 plays a critical role in preventing invasive disease following S. pyogenes infection of the respiratory tract.

Enhancing periodontal defences with nanofiber treatment: recent advances and future prospects.

The term periodontal disease is used to define diseases characterised by inflammation and regeneration of the gums, cementum, supporting bone, and periodontal ligament. The conventional treatment involves the combination of scaling, root planning, and surgical approaches which are invasive and can pose certain challenges. Intrapocket administration of nanofibers can be used for overcoming challenges which can help in speeding up the wound repair process and can also be used to promote osteogenesis. To help make drug delivery more effective, nanofibers are an interesting solution. Nanofibers are nanosized 3D structures that can fill the pockets and have excellent mucoadhesion which prolongs their retention time on the target site. Moreover, their structure mimics the natural extracellular matrix which enables nanomaterials to sense local biological conditions and start cellular-level reprogramming to produce the necessary therapeutic efficacy. In this review, the significance of intrapocket administration of nanofibers using recent research for the management of periodontitis has been discussed in detail. Furthermore, we have discussed polymers used for the preparation of nanofibers, nanofiber production methods, and the patents associated with these developments. This comprehensive compilation of data serves as a valuable resource, consolidating recent developments in nanofiber applications for periodontitis management into one accessible platform.

Nanoneuroscience: Cutting-edge Approach for Disease Management.

Neurological disorders (ND) have affected a major part of our society and have been a challenge for medical and biosciences for decades. However, many of these disorders haven't responded well to currently established treatment approaches. The fact that many active pharmaceutical ingredients can't get to their specified action site inside the body is one of the main reasons for this failure. Extracellular and intracellular central nervous system (CNS) barriers prevent the transfer of drugs from the blood circulation to the intended location of the action. Utilizing nanosized drug delivery technologies is one possible way to overcome these obstacles. These nano-drug carriers outperform conventional dosage forms in many areas, including good drug encapsulation capacity, targeted drug delivery, less toxicity, and enhanced therapeutic impact. As a result, nano-neuroscience is growing to be an intriguing area of research and a bright alternative approach for delivering medicines to their intended action site for treating different neurological and psychiatric problems. In this review, we have included a short overview of the pathophysiology of neurological diseases, a detailed discussion about the significance of nanocarriers in NDs, and a focus on its recent advances. Finally, we highlighted the patented technologies and market trends, including the predictive analysis for the years 2021-2028.

Emulgels: a promising topical drug delivery system for arthritis management and care.

BACKGROUND: Emulgels, hybrid formulations of emulsions and gels, offer distinct benefits viz. extended release, enhanced bioavailability, and targeted drug delivery to inflamed joints, thereby minimizing systemic side effects, and maximizing therapeutic efficacy in targeting the diseases. Oral medications and topical creams have limitations viz. limited permeation, efficacy, and side effects. Arthritis is a prevalent chronic inflammatory disorder affecting a substantial global population of about 350 million necessitating the exploration of innovative and effective treatment approaches. Inflammation of one or more joints in the body is referred to generally as arthritis, associated with joint discomfort, edema, stiffness, and decreased motion in the joints. MAIN PART: Emulgels further improve drug solubility and penetration into the affected tissues, augmenting the potential for disease-modifying effects. This review article comprehensively examines recent research for the potential of emulgels (micro- and nanoemulgels) as a potential therapeutic approach for arthritis management, thus showcasing their promising potential in precise treatment regimens. Despite the considerable progress in emulgel-based arthritis therapies, the review emphasizes the need for additional research and translation to clinical trials, thus ascertaining their long-term safety, efficacy, and cost-effectiveness compared to conventional treatments. CONCLUSION: With ongoing advancements in drug delivery, emulgels present an exciting frontier in arthritis-associated conditions, with the potential to revolutionize arthritis treatment and significantly enhance patient life's quality.

Chitosan and hyaluronic acid-based nanocarriers for advanced cancer therapy and intervention.

Cancer has become a major public health issue leading to one of the foremost causes of morbidity and death in the world. Despite the current advances in diagnosis using modern technologies and treatment via surgery or chemo- and radio-therapies, severe side effects or after-effects limit the application of these treatment modalities. Novel drug delivery systems have shown the potential to deliver chemotherapeutics directly to cancer cells, thus minimizing unnecessary exposure to healthy cells. Concurrently, to circumvent difficulties associated with conventional deliveries of cancer therapeutics, natural polysaccharides have gained attention for the fabrication of such deliveries owing to biocompatibility, low toxicity, and biodegradability. It has been exhibited that natural polysaccharides can deliver high therapeutic concentrations of the entrapped drug to the target cells by sustained and targeted release. Considering the immense potential of natural polymers, the present work focuses on naturally generated biopolymer carriers based on chitosan and hyaluronic acid. This review delineated on the role of chitosan and its derivation from renewable resources as a biocompatible, biodegradable, nonimmunogenic material with notable antitumor activity as a drug delivery carrier in oncotherapy. Moreover, hyaluronic acid, itself by its structure or when linked with other molecules contributes to developing promising pharmaceutical delivery systems to setback the restrictions related to conventional cancer treatment.

The SH-SY5Y cell line: a valuable tool for Parkinson's disease drug discovery.

INTRODUCTION: Owing to limited efficient treatment strategies for highly prevalent and distressing Parkinson's disease (PD), an impending need emerged for deciphering new modes and mechanisms for effective management. SH-SY5Y-based in vitro neuronal models have emerged as a new possibility for the elucidation of cellular and molecular processes in the pathogenesis of PD. SH-SY5Y cells are of human origin, adhered to catecholaminergic neuronal attributes, which consequences in imparting wide acceptance and significance to this model over conventional in vitro PD models for high-throughput screening of therapeutics. AREAS COVERED: Herein, the authors review the SH-SY5Y cell line and its value to PD research. The authors also provide the reader with their expert perspectives on how these developments can lead to the development of new impactful therapeutics. EXPERT OPINION: Encouraged by recent research on SH-SY5Y cell lines, it was envisaged that this in vitro model can serve as a primary model for assessing efficacy and toxicity of new therapeutics as well as for nanocarriers' capacity in delivering therapeutic agents across BBB. Considering the proximity with human neuronal environment as in pathogenic PD conditions, SH-SY5Y cell lines vindicated consistency and reproducibility in experimental results. Accordingly, exploitation of this standardized SH-SY5Y cell line can fast-track the drug discovery and development path for novel therapeutics.

Nano vs Resistant Tuberculosis: Taking the Lung Route.

Tuberculosis (TB) is among the top 10 infectious diseases worldwide. It is categorized among the leading killer diseases that are the reason for the death of millions of people globally. Although a standardized treatment regimen is available, non-adherence to treatment has increased multi-drug resistance (MDR) and extensive drug-resistant (XDR) TB development. Another challenge is targeting the death of TB reservoirs in the alveoli via conventional treatment. TB Drug resistance may emerge as a futuristic restraint of TB with the scarcity of effective Anti-tubercular drugs. The paradigm change towards nano-targeted drug delivery systems is mostly due to the absence of effective therapy and increased TB infection recurrent episodes with MDR. The emerging field of nanotechnology gave an admirable opportunity to combat MDR and XDR via accurate diagnosis with effective treatment. The new strategies targeting the lung via the pulmonary route may overcome the new incidence of MDR and enhance patient compliance. Therefore, this review highlights the importance and recent research on pulmonary drug delivery with nanotechnology along with prevalence, the need for the development of nanotechnology, beneficial aspects of nanomedicine, safety concerns of nanocarriers, and clinical studies.

Transform diabetes care with precision medicine.

Background and Aims: Diabetes is a global concern. This article took a closer look at diabetes and precision medicine. Methods: A literature search of studies related to the use of precision medicine in diabetes care was conducted in various databases (PubMed, Google Scholar, and Scopus). Results: Precision medicine encompasses the integration of a wide array of personal data, including clinical, lifestyle, genetic, and various biomarker information. Its goal is to facilitate tailored treatment approaches using contemporary diagnostic and therapeutic techniques that specifically target patients based on their genetic makeup, molecular markers, phenotypic traits, or psychosocial characteristics. This article not only highlights significant advancements but also addresses key challenges, particularly focusing on the technologies that contribute to the realization of personalized and precise diabetes care. Conclusion: For the successful implementation of precision diabetes medicine, collaboration and coordination among multiple stakeholders are crucial.

Potential diagnostic and prognostic biomarkers for breast cancer: A compiled review.

Breast cancer is one of the major reason for death of women worldwide. As per the International Agency for Research on Cancer (IARC) statistics, the number of cases of breast cancer is increasing year by year in many parts of the world. As per the recent global cancer burden figures, in 2020, there were 2.26 million incidences of breast cancer cases and it is one of the main causes of mortality due to cancer in women in the world. Biomarkers of breast cancer would prove to be very beneficial to screen women who are at higher risk and for detection of disease recurrence. Here, studies carried out on biomarkers of breast cancer and susceptibility to the disease have been reviewed. Various databases like Google Scholar, ScienceDirect and PubMed have been used for searching and majorly literature from the last 10 years have been considered. Potential biomarkers of breast cancer including blood based angiogenic factors, glycoprotein-based biomarkers, hormone receptor biomarkers and other biomarkers that were identified from various studies have been summarized.

Nano-approaches and Recent Advancements in Strategies to Combat Challenges Associated with Thyroid Cancer Therapies.

The prevalence of thyroid cancer (TC) is more common in women and is up to 43% in patients aged between 45-65 years. The battle against TC is hampered by the lack of effective diagnostic and therapeutic approaches. The effectiveness of surgical procedures, such as thyroidectomy and nutraceutical treatments, are accompanied by several difficulties and still require further research. Alternatively, the DNA-damaging traditional model of chemotherapy is linked to poor solubility, untoward systemic effects, and associated cytotoxicity, instituting an urgent need to establish a specialized, factual, and reliable delivery tool. In order to overcome the limitations of conventional delivery systems, nanotechnology-based delivery tools have shown the potential of articulating endless inherent implementations. The probable benefits of emerging nanotechnology-based diagnostic techniques include rapid screening and early illness diagnosis, which draws investigators to investigate and assess the possibility of this treatment for TC. Subsequently, organic (e.g., liposomes, polymer-based, and dendrimers) and inorganic (e.g., gold, carbon-based, mesoporous silica, magnetic, and quantum dots) NPs and hybrids thereof (liposome-silica, chitosan-carbon, and cell membrane-coated) have been projected for TC biomarker screening, therapy, and detection, providing better outcomes than traditional diagnostic and treatment techniques. Therefore, this review aims to offer a broad perspective on nanoplatform in TC, accompanied by present and potential future treatment options and screening techniques. The goal of cancer therapy has traditionally been to "search a thorn in a hayloft"; therefore, this article raises the possibility of treating TC using nano-oncotherapeutics, which might be useful clinically and will encourage future researchers to explore this tool's potential and drawbacks.

A Glycolipidated-liposomal peptide vaccine confers long-term mucosal protection against Streptococcus pyogenes via IL-17, macrophages and neutrophils.

Mucosally active subunit vaccines are an unmet clinical need due to lack of licensed immunostimulants suitable for vaccine antigens. Here, we show that intranasal administration of liposomes incorporating: the Streptococcus pyogenes peptide antigen, J8; diphtheria toxoid as a source of T cell help; and the immunostimulatory glycolipid, 3D(6-acyl) PHAD (PHAD), is able to induce long-lived humoral and cellular immunity. Mice genetically deficient in either mucosal antibodies or total antibodies are protected against S. pyogenes respiratory tract infection. Utilizing IL-17-deficient mice or depleting cellular subsets using antibodies, shows that the cellular responses encompassing, CD4+ T cells, IL-17, macrophages and neutrophils have important functions in vaccine-mediated mucosal immunity. Overall, these data demonstrate the utility of a mucosal vaccine platform to deliver multi-pronged protective responses against a highly virulent pathogen.

Biomacromolecule-based nanocarrier strategies to deliver plant-derived bioactive components for cancer treatment: A recent review.

The quest for safe chemotherapy has attracted researchers to explore anticancer potential of herbal medicines. Owing to upsurging evidence of herbal drug's beneficial effects, hopes are restored for augmenting survival rates in cancer patients. However, phytoconstituents confronted severe limitations in terms of poor absorption, low-stability, and low bioavailability. Along with toxicity issues associated with phytoconstituents, quality control and limited regulatory guidance also hinder the prevalence of herbal medicines for cancer therapy. Attempts are underway to exploit nanocarriers to circumvent the limitations of existing and new herbal drugs, where biological macromolecules (e.g., chitosan, hyaluronic acid, etc.) are established highly effective in fabricating nanocarriers and cancer targeting. Among the discussed nanocarriers, liposomes and micelles possess properties to cargo hydro- and lipophilic herbal constituents with surface modification for targeted delivery. Majorly, PEG, transferrin and folate are utilized for surface modification to improve bioavailability, circulation time and targetability. The dendrimer and carbon nanotubes responded in high-loading efficiency of phytoconstituent; whereas, SLN and nanoemulsions are suited carriers for lipophilic extracts. This review emphasized unveiling the latent potential of herbal drugs along with discussing on extended benefits of nanocarriers-based delivery of phytoconstituents for safe cancer therapy owing to enhanced clinical and preclinical outcomes without compromising safety.

From nature to therapy: Luteolin's potential as an immune system modulator in inflammatory disorders.

Inflammation is an essential immune response that helps fight infections and heal tissues. However, chronic inflammation has been linked to several diseases, including cancer, autoimmune disorders, cardiovascular diseases, and neurological disorders. This has increased interest in finding natural substances that can modulate the immune system inflammatory signaling pathways to prevent or treat these diseases. Luteolin is a flavonoid found in many fruits, vegetables, and herbs. It has been shown to have anti-inflammatory effects by altering signaling pathways in immune cells. This review article discusses the current research on luteolin's role as a natural immune system modulator of inflammatory signaling mechanisms, such as its effects on nuclear factor-kappa B, mitogen-activated protein kinases, Janus kinase/signal transducer and activator of transcription, and inflammasome signaling processes. The safety profile of luteolin and its potential therapeutic uses in conditions linked to inflammation are also discussed. Overall, the data point to Luteolin's intriguing potential as a natural regulator of immune system inflammatory signaling processes. More research is needed to fully understand its mechanisms of action and possible therapeutic applications.

Recent Update on Nanoemulsion Impregnated Hydrogel: a Gleam into the Revolutionary Strategy for Diffusion-Controlled Delivery of Therapeutics.

Since earlier times, dermatological remedies have been utilized to treat diseases associated with pain, irritation, and skin conditions. Compared to other routes of drug delivery, topical delivery of drugs offers several benefits. Scientists are investigating different alterations in dosage forms in addition to existing topical formulations such as ointments, gels, creams, lotions, and ointments to significantly improve the permeation of drugs and enhance the pharmacological efficacy of medications that are poorly absorbed via the skin. Conventional formulations have a plethora of problems viz. poor absorption, no target specificity, low spreadability, and inadequate bioavailability which leads the researchers toward developing novel formulations like nanoemulsions. The nanoemulsion can enhance the gradient in concentration and thermodynamic movement toward the epidermis and enhance the penetration of its constituents. However, due to its difficult application, nanoemulsion's lower viscosity limited its use in transdermal delivery. Thus, the development of nanoemulsion-based hydrogels has shown to be a successful strategy for removing obstacles from existing drug formulations. The simple application, expedient spreadability, non-stickiness, safety, and effectiveness of nanoemulsion-based hydrogel have led to substantial growth in their research in recent years. This review gives a brief idea about the prevalence of skin diseases, skin as an obstacle for drug delivery, and recent research insights to combat these obstacles. The work highlights the mechanism of drug release via nanoemulsion, hydrogels, and nanoemulsion-based hydrogels with reference to recent research on hydrophobic and hydrophilic drugs.

Miniaturized Polymeric Systems for the Intravaginal Gene Therapies: Recent Update on Unconventional Delivery.

The prevalence of vaginal infection is increasing among women, especially at reproductive age. For proper eradication of infection, the effective concentration of a drug is required at the infection site. Therefore, local delivery is recommended to exert a direct therapeutic effect at the site action that causes a reduction in dose and side effects. The main focus of vaginal drug delivery is to enhance retention time and patient compliance. The high recurrence rate of vaginal infection due to the lack of effective treatment strategies opens the door for new therapeutic approaches. To combat these setbacks, intravaginal gene therapies have been investigated. High attention has been gained by vaginal gene therapy, especially for sexually transmitted infection treatment. Despite much research, no product is available in the market, although in vitro and preclinical data support the vaginal route as an effective route for gene administration. The main focus of this review is to discuss the recent advancement in miniaturized polymeric systems for intravaginal gene therapies to treat local infections. An overview of different barriers to vaginal delivery and challenges of vaginal infection treatment are also summarised.

Polymeric epitope-based vaccine induces protective immunity against group A Streptococcus.

Group A Streptococcus (Strep A) is a life-threatening human pathogen with no licensed vaccine. Here, we used a biopolymer particle (BP) approach to display repeats of Strep A vaccine candidate peptides p*17 and K4S2 derived from M and non-M protein, respectively. BPs densely displaying both peptides (BP-p*17-S2) were successfully assembled in one-step inside an engineered endotoxin-free Escherichia coli strain. Purified BP-p*17-S2 showed a spherical core-shell morphology with a biopolymer core and peptide shell. Upon formulation with aluminum hydroxide as adjuvant, BP-p*17-S2 exhibited a mean diameter of 2.9 µm and a positive surface charge of 22 mV. No cytotoxicity was detected when tested against HEK-293 cells. Stability studies showed that BP-p*17-S2 is ambient-temperature stable. Immunized mice showed no adverse reactions, while producing high titers of peptide specific antibodies and cytokines. This immune response could be correlated with protective immunity in an animal model of infection, i.e. intranasal challenge of mice with Strep A, where a significant reduction of >100-fold of pathogen burden in nose-associated lymphoid tissue, lung, and spleen was obtained. The cost-effective scalable manufacture of ambient-temperature stable BPs coated with Strep A peptides combined with their immunogenic properties offer an attractive alternative strategy to current Strep A vaccine development.

Recent progress of targeted nanocarriers in diagnostic, therapeutic, and theranostic applications in colorectal cancer.

Cancer at the lower end of the digestive tract, colorectal cancer (CRC), starts with asymptomatic polyps, which can be diagnosed as cancer at a later stage. It is the fourth leading cause of malignancy-associated mortality worldwide. Despite progress in conventional treatment strategies, the possibility to overcome the mortality and morbidity issues with the enhancement of the lifespan of CRC patients is limited. With the advent of nanocarrier-based drug delivery systems, a promising revolution has been made in diagnosis, treatment, and theranostic purposes for cancer management. Herein, we reviewed the progress of miniaturized nanocarriers, such as liposomes, niosomes, solid lipid nanoparticles, micelles, and polymeric nanoparticles, employed in passive and active targeting and their role in theranostic applications in CRC. With this novel scope, the diagnosis and treatment of CRC have proceeded to the forefront of innovation, where specific characteristics of the nanocarriers, such as processability, flexibility in developing precise architecture, improved circulation, site-specific delivery, and rapid response, facilitate the management of cancer patients. Furthermore, surface-engineered technologies for the nanocarriers could involve receptor-mediated deliveries towards the overexpressed receptors on the CRC microenvironment. Moreover, the potential of clinical translation of these targeted miniaturized formulations as well as the possible limitations and barriers that could impact this translation into clinical practice were highlighted. The advancement of these newest developments in clinical research and progress into the commercialization stage gives hope for a better tomorrow.