Exploring the role of SOX 2 and OCT 4 in the pathogenesis of gliomatosis peritonei: the clinicopathological profile of eleven cases.

Objective: Gliomatosis peritonei (GP) is a rare entity characterized by multiple mature glial tissue implants in association with ovarian teratomas in the peritoneum and omentum. To date, only 100 cases have been published. Not much is known about the origin, clinicopathological profile or prognosis of GP. SOX2 and OCT4 are recently recognized markers of embryonic stem cell differentiation. Here, the role of SOX2 and OCT4 in the pathogenesis of 11 cases of GP are reported and clinicopathological factors are described. Material and Methods: This was a retrospective study of six years duration (2017-2022). All the cases of GP were retrieved from archives, the diagnosis was confirmed and clinicopathological factors were noted. Immunohistochemical (IHC) investigation for glial fibrillary acid protein (GFAP) and S100 was noted wherever available. IHC for SOX2 and OCT4 was performed using an avidin-biotin technique. Results: There were 11 cases of GP identified. The median age was 29 years and 1/11 cases had nodal gliomatosis as well. There were eight cases of immature teratoma and three cases of mature cystic teratoma. SOX2 was positive in all foci of GP, while OCT4 was negative. These foci were also positive for GFAP and S100. Conclusion: A possibility of GP should be considered as a differential, clinically and radiologically, in cases of omental nodularity. Adequate sampling at the time of surgery is essential to rule out metastasis or growing teratoma syndrome. SOX2, a stem cell marker inducing neural differentiation, may play a crucial role in the development of GP in association with other transcription factors.

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.

Intelligent Drug Delivery: Pioneering Stimuli-Responsive Systems to Revolutionize Disease Management- An In-depth Exploration.

In recent years, there has been an escalating interest in stimuli-responsive drug delivery systems (SRDDS) due to their ability to revolutionize the delivery of therapeutics. SRDDSs offer a multitude of benefits in comparison to conventional drug delivery systems (DDS), including spatiotemporal control of drug release, targeted delivery, and improved therapeutic efficacy. The development of various classes of stimuli-responsive DDS, such as pH-responsive, temperature-responsive, photo-responsive, redox responsive systems, has been propelled by advances in materials science, nanotechnology, and biotechnology. These systems exploit specific environmental or physiological cues to trigger drug release in a precisely controlled manner, making them highly promising for the treatment of various diseases. In this review article, an in-depth exploration of the principles, mechanisms, and applications of SRDDS in the context of diverse pathologies such as cancer, arthritis, Alzheimer's disease, atherosclerosis and tissue engineering has been provided. Furthermore, this article delves into the discussion of recent patents, market overview and the progress of research in clinical trials. Overall, this article underscores the transformative potential of SRDDS in enabling personalized, precise, and effective drug delivery for the treatment of the above-mentioned diseases.

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.

Role of Albumin as a Targeted Drug Carrier in the Management of Rheumatoid Arthritis: A Comprehensive Review.

An endogenous transporter protein called albumin interacts with the Fc receptor to provide it with multiple substrate-binding domains, cell membrane receptor activation, and an extended circulating half-life. Albumin has the remarkable ability to bind with receptors viz. secreted protein acidic and rich in cysteine (SPARC) and scavenger protein-A (SR-A) that are overexpressed during rheumatoid arthritis (RA), enabling active targeting of the disease site instead of requiring specialized substrates to be added to the nanocarrier. RA, a chronic autoimmune illness, is characterized by the presence of a severe inflammatory response. RA patients have low serum albumin concentration, which signifies the high uptake of albumin at the inflammatory sites, giving a rationale to use albumin as a drug carrier for RA therapy. Albumin has the capacity for both passive and active targeting. It is an abundantly available protein in the bloodstream showing excellent cellular compatibility, degradability in biological tissues, nonantigenicity, and safety. There are three strategies of albumin mediated drug delivery as encapsulating therapeutics in albumin nanoparticles, chemically conjugating drugs with functional proteins, and albumin itself which is used as a targeting ligand to deliver drugs specifically to cells or tissues that express albumin-binding receptors. In the current review, an attempt has been made to highlight the significant evidence of albumin as a drug delivery carrier for the safe and effective management of RA. Evidence has been provided in the form of recent research advances, clinical trials, and patents. Additionally, this review will outline the prospective for the potential utilization of albumin as a drug vehicle for RA and suggest possible future avenues to provide the perspective for subsequent studies.

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.

Unveiling the Mpox menace: exploring the intricacies of a zoonotic virus and clinical implications.

Mpox (formerly known as monkeypox) is an orthopoxvirus based zoonotic infection that induces a smallpox-like human illness. Since the Democratic Republic of the Congo reported the first human case of mpox in 1970, the disease has proliferated to other areas of Africa, predominantly the West, and Central, with instances recently confirmed outside of Africa. Reports of cases of mpox in 2022 have brought into light its re-emergence. Even though the smallpox vaccine protects against the mpox virus, new nonimmune generations contribute to the rising prevalence of the cases. People are coming into contact with potential hosts as a result of environmental factors, raising the probability of animal-to-human transmission. Mpox poses a more serious threat to previously unaffected nations as it is showing up in data provided by governmental bodies due to increased transmission risk brought on by globalization, armed conflict, and environmental factors. In this article, we have extensively covered the virology, etiology, and epidemiology of the disease. Various gene studies, recent drugs studied, and clinical trials pertaining to mpox have been incorporated in this review. Additionally, we have compiled a comprehensive analysis of various systematic reviews and meta-analyses concerning pregnancies complicated by mpox, retrospective studies examining mpox and HIV-coinfection, mpox in conjuction with SARS-CoV-2, and HIV coinfection, as well as case studies exploring the implications of mpox manifestations in conjunction with syphilis, gonorrhoea, myocarditis, and neuroinflammatory implications.

Recent advancements in the expedition of microneedles: from lab worktops to diagnostic care centers.

Microneedle (MN) technology plays a significant role in bioengineering as it allows for minimally invasive exposure to the skin via the non-invasive procedure, increased drug permeability, and improved biological molecule detectability in the epidermal layers, all while improving therapeutic safety and effectiveness. However, MNs have several significant drawbacks, including difficulty scaling up, variability in drug delivery pattern regarding the skin's external environment, blockage of dermal tissues, induction of inflammatory response at the administration site, and limitation of dosing based on the molecular weight of drug and size. Despite these drawbacks, MNs have emerged as a special transdermal theranostics instrument in clinical research to assess physiological parameters. Bioimaging technology relies on microneedles that can measure particular analytes in the extracellular fluid effectively by crossing the stratum corneum, making them "a unique tool in diagnostics detection and therapeutic application inside the body." This review article discusses the recent advances in the applications especially related to the diagnostics and toxicity challenges of microneedles. In addition, this review article discusses the clinical state and commercial accessibility of microneedle technology-based devices in order to provide new information to scientists and researchers.

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.

Central composite design-based optimization, fabrication, and pharmacodynamic assessment of sulfasalazine-loaded lipoidal nanoparticle-based hydrogel for the management of rheumatoid arthritis.

Rheumatoid arthritis is a progressive, chronic, immunological, and inflammatory disorder that is distinguished by joint inflammation, joint tenderness, and synovial joint destruction. The study aimed to fabricate sulfasalazine-loaded solid lipid nanoparticle (SLN)-based gels for rheumatoid arthritis management. The SLNs were fabricated with the melt emulsification technique by employing central composite design (CCD) for SLNs optimization. The optimized formulation of SLNs (FF-1) showed particle size and drug entrapment efficiency of 117.25 nm ± 1.67 and 94.05% ± 1.05, respectively. To scrutinize the outcome of the independent variable on responses; model graphs and the polynomial equation obtained from the Design-Expert were used. The surface morphology studies of SLNs revealed a smooth surface with a slightly asymmetric shape. In vitro drug release of the optimized formulation (FF1) had shown a maximum release of up to ~ 91.89% ± 2.12 over 24 h. The optimized FF1 formulation was subsequently gelled using 1% w/v Carbopol 934 and subjected to ex vivo permeation that displayed 8.01 mg/cm2 ± 0.24 and 7.49 mg/cm2 ± 0.86 amount of drug permeated up to 24 h and 10 h from SLNs gel and plain gel, respectively. In vivo studies manifested a considerable reduction in the paw thickness (*p < 0.0001) and an arthritic score (*p < 0.0001) of the sulfasalazine SLN gel as compared to plain gel. Further, pro-inflammatory cytokines, viz. TNF-α, IL-1, and IL-6 levels, were significantly inhibited (p < 0.0001) by sulfasalazine SLN-based gel that exhibited substantial anti-inflammatory effects. In conclusion, sulfasalazine-loaded SLN-based gel showed sustained release of drug for up to 24 h and can be considered suitable as a topical application for rheumatoid arthritis management.

Preclinical assessment of nanostructured liquid crystalline particles for the management of bacterial keratitis: in vivo and pharmacokinetics study.

The research work was driven to develop, optimize, and characterize novel nanostructured liquid crystalline particles as carriers for the ocular delivery of vancomycin. The formulations were developed by fragmenting the cubic crystalline phase of glycerol monooleate, water, and poloxamer 407. A four-factor, three-level Taguchi statistical experimental design was constructed to optimize the formulation. Formulations exhibited internal-cubic structure of the vesicles with particle size in the range of 51.11 ± 0.96 nm to 158.73 ± 0.46 nm and negative zeta potential. Ex vivo transcorneal permeation studies demonstrated that the optimized cubosomes had a 2.4-fold increase in apparent permeability co-efficient as compared to vancomycin solution, whereas in vivo studies in rabbits demonstrated that the severity of keratitis was considerably lowered on day 3 with optimized cubosomes. Ocular pharmacokinetic studies evaluated the level of drug in aqueous humor, and results revealed that the time to peak concentration (Tmax) of vancomycin-loaded cubosomal formulation was about 1.9-fold higher and mean residence time was 2.2-fold greater than vancomycin solution. Furthermore, histological examination revealed that the corneal layers displayed well-maintained morphology without any stromal swelling, consequently indicating the safety of formulation. It could be concluded that the developed nanostructured liquid crystalline particles of vancomycin demonstrated improved pre-ocular residence time, increased permeability, reduced dosing frequency, controlled drug release, and reduced systemic side-effects. Results manifested that the developed vancomycin-loaded cubosomes could be a promising novel ocular carrier and an ideal substitute for conventional eye drops for the management of bacterial-keratitis.

Investigating nanostructured liquid crystalline particles as prospective ocular delivery vehicle for tobramycin sulfate: Ex vivo and in vivo studies.

Tobramycin remains the anchor drug for bacterial keratitis treatment and management; however, unlike other aminoglycosides, it does not pass through the gastrointestinal tract. The aim of the current investigation was to formulate tobramycin-loaded nanostructured liquid crystalline particles as an ophthalmic drug delivery system to ameliorate its preocular residence duration and ophthalmic bioavailability. Tobramycin cubosomes were fabricated by liquid-lipid monoolein, water, and poloxamer 407 as a stabilizer. Corneal penetration studies exhibited that the apparent permeation coefficient of tobramycin cubosomes was nearly 3.6-fold greater than marketed tobramycin eye drops. Ocular in vivo analysis performed in rabbits' eyes manifested that the intensity of bacterial keratitis was reduced on day 3, and on day 5, the manifestations were considerably mitigated with tobramycin cubosomes as compared to marked eye drops. Pharmacokinetic study of rabbit aqueous humor demonstrated that the area under curve and the peak concentration of optimized cubosomes were 3.1-fold and 3.3-fold, respectively, which was significantly higher than marketed eye drops. Moreover, histopathological studies illustrated the existence of normal ocular structures, thus indicating that there was no damage to the corneal epithelium or stromal layer. Consequently, the results acquired demonstrated that tobramycin-loaded cubosomal formulation could be a propitious lipid-based nanodelivery system that would enhance retention time and corneal permeability contrast to commercial eye drops.

Investigating The Retention Potential of Chitosan Nanoparticulate Gel: Design, Development, In Vitro & Ex Vivo Characterization.

INTRODUCTION: The main purpose of the research was to develop, optimize and characterize tobramycin sulphate loaded chitosan nanoparticles based gel in order to ameliorate its therapeutic efficacy, precorneal residence time, stability, targeting and to provide controlled release of the drug. METHODS: Box-Behnken design was used to optimize formulation by 3-factors (chitosan, STPP and tween 80) and 3-levels. Developed formulation was subjected for characterizations such as shape and surface morphology, zeta potential, particle size, in vitro drug release studies, entrapment efficiency of drug, visual inspection, pH, viscosity, spreadability, drug content, ex vivo transcorneal permeation studies, ocular tolerance test, antimicrobial studies, isotonicity evaluation and histopathology studies. RESULTS: Based on the evaluation parameters, the optimized formulation showed a particle size of 43.85 ± 0.86 nm and entrapment efficiency 91.56% ± 1.04, PDI 0.254. Cumulative in vitro drug release was up to 92.21% ± 1.71 for 12 hours and drug content was found between 95.36% ± 1.25 to 98.8% ± 1.34. TEM analysis unfolded spherical shape of nanoparticles. TS loaded nanoparticulate gel exhibited significantly higher transcorneal permeation as well as bioadhesion when compared with marketed formulation. Ocular tolerance was evaluated by HET-CAM test and formulation was non-irritant and well-tolerated. Histopathology studies revealed that there was no evidence of damage to the normal structure of the goat cornea. As per ICH guidelines, stability studies were conducted and were subjected for 6 months. CONCLUSION: Results revealed that the developed formulation could be an ideal substitute for conventional eye drops for the treatment of bacterial keratitis.

Protein Based Nanostructures for Drug Delivery.

The key role of protein based nanostructures has recently revolutionized the nanomedicine era. Protein nanoparticles have turned out to be the major grounds for the transformation of different properties of many conventional materials by virtue of their size and greater surface area which instigates them to be more reactive to some other molecules. Protein nanoparticles have better biocompatibilities and biodegradability and also have the possibilities for surface modifications. These nanostructures can be synthesized by using protein like albumin, gelatin, whey protein, gliadin, legumin, elastin, zein, soy protein, and milk protein. The techniques for their fabrication include emulsification, desolvation, complex coacervation, and electrospray. The characterization parameters of protein nanoparticles comprise particle size, particle morphology, surface charge, drug loading, determination of drug entrapment, and particle structure and in vitro drug release. A plethora of protein nanoparticles applications via different routes of administration are explored and reported by eminent researchers which are highlighted in the present review along with the patents granted for protein nanoparticles as drug delivery carriers.

Role of Nanotechnology in Cosmeceuticals: A Review of Recent Advances.

Nanotechnology manifests the progression in the arena of research and development, by increasing the efficacy of the product through delivery of innovative solutions. To overcome certain drawbacks associated with the traditional products, application of nanotechnology is escalating in the area of cosmeceuticals. Cosmeceuticals are regarded as the fastest growing segment of the personal care industry and the use has risen drastically over the years. Nanocosmeceuticals used for skin, hair, nail, and lip care, for conditions like wrinkles, photoaging, hyperpigmentation, dandruff, and hair damage, have come into widespread use. Novel nanocarriers like liposomes, niosomes, nanoemulsions, microemulsion, solid lipid nanoparticles, nanostructured lipid carrier, and nanospheres have replaced the usage of conventional delivery system. These novel nanocarriers have advantages of enhanced skin penetration, controlled and sustained drug release, higher stability, site specific targeting, and high entrapment efficiency. However, nanotoxicological researches have indicated concern regarding the impact of increased use of nanoparticles in cosmeceuticals as there are possibilities of nanoparticles to penetrate through skin and cause health hazards. This review on nanotechnology used in cosmeceuticals highlights the various novel carriers used for the delivery of cosmeceuticals, their positive and negative aspects, marketed formulations, toxicity, and regulations of nanocosmeceuticals.