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Introduction: Preterm deliveries contribute to major morbidity and mortality in developing countries. They are a leading cause of admission in neonatal care units. It is a major hindrance to the attainment of the Sustainable Development Goal (SDG)-3 targets given its high contribution to neonatal mortality. Early detection of its risk factors and advances in the management have ensured better survival of preterm births. This study was conducted to determine the prevalence, underlying causes, morbidity patterns and outcome of preterm admissions to a neonatal intensive care unit (NICU) of a tertiary care center in Combined Military Hospital (CMH) Sylhet. Material and Methods: A descriptive study was conducted in CMH Sylhet from July 2018 to June 2020. All live preterm babies delivered at CMH Sylhet during the study period were included. Information obtained included gestational age at birth, gender, cause for preterm birth, problems during admission and outcome. Results: During this period, a total of 662 neonates were admitted out of which 107 (16.2%) were preterm with gestational ages ranging from 27 completed weeks to less than 37 completed weeks with a mean gestational age 33.2 weeks (± 2.7 weeks) and birth weights from 800 - 2600 gm with a mean of 2100 gm (± 700 gm). There were 52 males and 55 females (M: F 0.95). One hundred and thirty three (20.1%) were delivered by normal vaginal delivery while 529 (79.9%) were delivered by Caesarean section. The duration of hospital stay ranged from 1 - 45 days, with a mean duration of 15 days (± 9.2 days). The commonest reason for prematurity was premature rupture of membrane (PROM) (39.3%) followed by gestational diabetes mellitus (GDM) (35.5%), hypertensive disorders in pregnancy (30.8%), multiple pregnancy (29.9%) and inadequate ante natal care (ANC) (20.6%). The commonest morbidity in the patients in the present study was neonatal jaundice (90.7%) followed by respiratory problems (78.5%), sepsis (17.8%) and congenital heart disease (CHD) (15.9%). Case fatality rate for patients with respiratory distress syndrome (7.7%) and sepsis (5.3%) were common. Overall survival rate was 91.6% and was significantly (p <0.001) higher in the moderate to late preterm category compared to the very preterm and extremely preterm births. Conclusion: PROM, GDM, hypertensive disorders in pregnancy, multiple pregnancy and inadequate ante natal care were significantly associated with preterm birth. Neonatal jaundice, respiratory problems, sepsis and CHD were common morbidities observed. Case fatality rate was significant in neonates with respiratory distress syndrome and sepsis and overall survival rate was 91.6%. So, at-risk mothers should receive intensified antenatal care to mitigate preterm birth. [ABSTRACT FROM AUTHOR]

This research letter focuses on tourist behavior and tourism business operators' contributions to rural mountain region economic growth and sustainable development when using social media. Data were collected from 43 interviews from different tourism business operators, and a questionnaire survey of 576 tourists from the Gilgit-Baltistan, Pakistan. Drawing on development communication theory, the study reveals that there is a positive relationship between the tourists' intentions and rural mountain region sustainable development. The study also reveals that most tourists are willing to pay more taxes when touring mountain regions. The real business outcomes from tourism business operators show that rural mountain region tourism creates better employment opportunities for the rural population. All tourists demonstrated the motivation to take part in rural mountain region sustainable development while touring rural locations. The study also offers policy implications. [ABSTRACT FROM AUTHOR]

Early detection of disease remains a crucial challenge in medicine. Delayed diagnosis often leads to limited treatment options, increased disease progression, and unfortunately, even death in some cases. To address this, the need for rapid, cost-effective, and noninvasive diagnostic tools is paramount. In recent years, electrochemical nanosensor-based point-of-care diagnostic tools have emerged as promising tools for various fields, with significant interest in their biological and chemical applications. These tiny sensors, utilizing nanoparticles and chemical agents, can detect and monitor physical components like disease biomarkers at the nanoscale, offering a unique advantage rarely found in other diagnostic methods. This unprecedented sensitivity has made them highly sought-after tools for biological applications, particularly in disease diagnosis. This review focuses specifically on electrochemical nanosensors and their potential as diagnostic tools in medicine. We will delve into their properties, applications, current advancements, and existing limitations., (© 2024 Wiley Periodicals LLC.)

In recent studies, lipid nanoparticles have attracted attention as drug delivery systems owing to their preeminent potential in achieving the desired bioavailability of biopharmaceutics (BCS) class II and class IV drugs. The current debate concerns the bioavailability of these poorly absorbed drugs with their simultaneous oral degradation. Lipid nanoparticles, including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), are lipid-based carrier systems that can effectively encapsulate both lipophilic and hydrophilic drugs, offering versatile drug delivery systems. The unique properties of lipids (biodegradability and biocompatibility) and their transportation pathways enhance the biological availability of drugs. These particles can increase the gastrointestinal absorption and solubilization of minimally bioavailable drugs via a selective lymphatic pathway. This review mainly focuses on providing a brief update on lipid nanoparticles (LNPs) that synergistically increase the bioavailability of limited permeable drugs and highlight the transversal mechanisms of LNPs across the gastrointestinal hurdles, transmembrane absorption, transport kinetics, and computational tools. Finally, the present hurdles and future perspectives of LNPs for oral drug delivery systems are discussed.

Liver fibrosis (LF) occurs when the liver tissue responds to injury or inflammation by producing excessive amounts of scar tissue, known as the extracellular matrix. This buildup stiffens the liver tissue, hinders blood flow, and ultimately impairs liver function. Various factors can trigger this process, including bloodborne pathogens, genetic predisposition, alcohol abuse, non-steroidal anti-inflammatory drugs, non-alcoholic steatohepatitis, and non-alcoholic fatty liver disease. While some existing small-molecule therapies offer limited benefits, there is a pressing need for more effective treatments that can truly cure LF. RNA therapeutics have emerged as a promising approach, as they can potentially downregulate cytokine levels in cells responsible for liver fibrosis. Researchers are actively exploring various RNA-based therapeutics, such as mRNA, siRNA, miRNA, lncRNA, and oligonucleotides, to assess their efficacy in animal models. Furthermore, targeted drug delivery systems hold immense potential in this field. By utilizing lipid nanoparticles, exosomes, nanocomplexes, micelles, and polymeric nanoparticles, researchers aim to deliver therapeutic agents directly to specific biomarkers or cytokines within the fibrotic liver, increasing their effectiveness and reducing side effects. In conclusion, this review highlights the complex nature of liver fibrosis, its underlying causes, and the promising potential of RNA-based therapeutics and targeted delivery systems. Continued research in these areas could lead to the development of more effective and personalized treatment options for LF patients., (© 2024. Controlled Release Society.)

The oral and nasal cavities serve as critical gateways for infectious pathogens, with microorganisms primarily gaining entry through these routes. Our first line of defense against these invaders is the mucosal membrane, a protective barrier that shields the body's internal systems from infection while also contributing to vital functions like air and nutrient intake. One of the key features of this mucosal barrier is its ability to protect the physiological system from pathogens. Additionally, mucosal tolerance plays a crucial role in maintaining homeostasis by regulating the pH and water balance within the body. Recognizing the importance of the mucosal barrier, researchers have developed various mucosal formulations to enhance the immune response. Mucosal vaccines, for example, deliver antigens directly to mucosal tissues, triggering local immune stimulation and ultimately inducing systemic immunity. Studies have shown that lipid-based formulations such as liposomes and virosomes can effectively elicit both local and systemic immune responses. Furthermore, mucoadhesive polymeric particles, with their prolonged delivery to target sites, have demonstrated an enhanced immune response. This Review delves into the critical role of material selection and delivery approaches in optimizing mucosal immunity.

Disorders of the central nervous system (CNS) which include a wide range of neurodegenerative and neurological conditions have become a serious global issue. The presence of CNS barriers poses a significant challenge to the progress of designing effective therapeutic delivery systems, limiting the effectiveness of drugs, genes, and other therapeutic agents. Natural nanocarriers present in biological systems have inspired researchers to design unique delivery systems through biomimicry. As natural resource derived delivery systems are more biocompatible, current research has been focused on the development of delivery systems inspired by bacteria, viruses, fungi, and mammalian cells. Despite their structural potential and extensive physiological function, making them an excellent choice for biomaterial engineering, the delivery of nucleic acids remains challenging due to their instability in biological systems. Similarly, the efficient delivery of genetic material within the tissues of interest remains a hurdle due to a lack of selectivity and targeting ability. Considering that gene therapies are the holy grail for intervention in diseases, including neurodegenerative disorders such as Alzheimer's disease, Parkinson's Disease, and Huntington's disease, this review centers around recent advances in bioinspired approaches to gene delivery for the prevention of CNS disorders.

Objectives: The field of dentistry is characterised by its substantial energy consumption and resource utilisation, resulting in a notable ecological footprint. Thus, sustainability in dentistry is an important but underresearched concern. The influence of public pressure on sustainability has been extensively studied across other industries; nevertheless, there is a dearth of research examining its impact on the dental sector specifically in Saudi Arabia. The current study conducted the first-ever survey in Saudi Arabia to investigate the prevailing attitudes with regard to sustainable dentistry amongst the general population of the country., Methods: This was an online cross-sectional observational survey conducted in Riyadh, Saudi Arabia. A self-administered online questionnaire was distributed to adults aged 18 years and older, of both genders, from March to April 2023. The study obtained appropriate ethical approval., Results: Participants expressed a positive attitude with regard to sustainable dentistry and demonstrated their openness regarding compromising in terms of time, convenience, cost, and even the appearance of their teeth in order to minimise the environmental impact resulting from dental procedures. It is also evident that a correlation exists between gender-associated beliefs and proenvironmental behaviour, particularly in the context of sustainable dentistry and related environmental intentions in Saudi Arabia., Conclusions: The findings of this study represent an important complement to the existing sustainability knowledge and understanding in dentistry, which will be helpful for policymakers as well as dental professionals to develop or modify policy, regulation, and professional curriculum., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Breast cancer is the most prevalent cancer among women and the leading cause of cancer-related deaths in this population. Recent advances in Immunotherapy, or combined immunotherapy, offering a more targeted and less toxic approach, expand the survival rate of patients more than conventional treatment. Notably, hydrogels, a versatile platform provided promising avenues to combat breast cancer in preclinical studies and extended to clinical practices. With advantages such as the alternation of tumor microenvironment, immunomodulation, targeted delivery of therapeutic agents, and their sustained release at specific sites of interest, hydrogels can potentially be used for the treatment of breast cancer. This review highlights the advantages, mechanisms of action, stimuli-responsiveness properties, and recent advancements of hydrogels for treating breast cancer immunotherapy. Moreover, post-treatment and its clinical translations are discussed in this review. The integration of hydrogels in immunotherapy strategies may pave the way for more effective, personalized, and patient-friendly approaches to combat breast cancer, ultimately contributing to a brighter future for breast cancer patients., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The objective of this present work was to develop and optimize oil-in-water (O/W) emulsion-based gels, namely emulgels that allow maximum topical drug delivery while having desired microstructure and acceptable physical stability. Emulgels containing 2.0 wt% lidocaine were prepared using various concentrations (0.75-5.0 wt%) of Sepineo P600. Their droplet size distribution, physical stability, rheological behaviors, in vitro drug release, and skin permeation profiles were evaluated. Results show that the concentration of Sepineo P600 significantly influenced the microstructure, rheology, and physical stability of the emulgel formulations. The physico-chemical properties also reveals that at least 1.0 wt% Sepineo P600 was needed to produce stable emulgel formulations. All formulations exhibited non-Newtonian shear-thinning properties which are desirable for topical applications. Both the release and permeation rates decreased with increasing viscosity and rigidity of the formulation. The lower the complex modulus of the emulgels, the higher the steady-state flux of the drug through the skin. Adding Sepineo P600 to emulgel systems resulted in increased rheological properties, which in turn slowed the diffusion of the drug for in vitro release. Although as expected skin permeation was rate limiting since in vitro release was 3 to 4 log-fold faster than skin flux. However, an interesting finding was that the derived skin/vehicle partition coefficient suggested the ionic interaction between lidocaine and Sepineo polymer reducing the free drug, i.e., thermodynamic activity and hence the flux with increasing Sepineo P600 concentration. Overall, this study has provided us with valuable insights into understanding the relationship between the microstructure (rheology), physical stability and skin drug delivery properties which will help to design and optimize topical emulgel formulations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Abu Zayed Md Badruddoza, Thean Yeoh, Dana Gates, and Jaymin Shah are employees and shareholders of Pfizer Inc. The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with a high mortality rate due to limited treatment options. Current therapies cannot effectively reverse the damage caused by IPF. Research suggests that promoting programmed cell death (apoptosis) in myofibroblasts, the key cells driving fibrosis, could be a promising strategy. However, inducing apoptosis in healthy cells like epithelial and endothelial cells can cause unwanted side effects. This project addresses this challenge by developing a targeted approach to induce apoptosis specifically in myofibroblasts. We designed liposomes (LPS) decorated with peptides that recognize VCAM-1, a protein highly expressed on myofibroblasts in fibrotic lungs. These VCAM1-targeted LPS encapsulate Venetoclax (VNT), a small molecule drug that inhibits BCL-2, an anti-apoptotic protein. By delivering VNT directly to myofibroblasts, we hypothesize that VCAM1-VNT-LPS can selectively induce apoptosis in these cells, leading to reduced fibrosis and improved lung function. We successfully characterized VCAM1-VNT-LPS for size, surface charge, and drug loading efficiency. Additionally, we evaluated their stability over three months at different temperatures. In vitro and in vivo studies using a bleomycin-induced mouse model of lung fibrosis demonstrated the therapeutic potential of VCAM1-VNT-LPS. These studies showed a reduction in fibrosis-associated proteins (collagen, α-SMA, VCAM1) and BCL-2, while simultaneously increasing apoptosis in myofibroblasts. These findings suggest that VCAM1-targeted delivery of BCL-2 inhibitors using liposomes presents a promising and potentially selective therapeutic approach for IPF., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Continuous and aberrant activation of myofibroblasts is the hallmark of pathological fibrosis (e.g., abnormal wound healing). The deposition of excessive extracellular matrix (ECM) components alters or increases the stiffness of tissue and primarily accounts for multiple organ dysfunctions. Among various proteins, Cadherin-11 (CDH11) has been reported to be overexpressed on myofibroblasts in fibrotic tissues. Anti-apoptotic proteins such as (B cell lymphoma-2) (BCL-2) are also upregulated on myofibroblasts. Therefore, we hypothesize that CDH11 could be a targeted domain for cell-specific drug delivery and targeted inhibition of BCL-2 to ameliorate the development of fibrosis in the skin. To prove our hypothesis, we have developed liposomes (LPS) conjugated with CDH11 neutralizing antibody (antiCDH11) to target cell surface CDH11 and loaded these LPS with a BCL-2 inhibitor, Navitoclax (NAVI), to induce apoptosis of CDH11 expressing fibroblasts. The developed LPS were evaluated for physicochemical characterization, stability, in vitro therapeutic efficacy using dermal fibroblasts, and in vivo therapeutic efficacy in bleomycin-induced skin fibrosis model in mice. The findings from in vitro and in vivo studies confirmed that selectivity of LPS was improved towards CDH11 expressing myofibroblasts, thereby improving therapeutic efficacy with no indication of adverse effects. Hence, this novel research work represents a versatile LPS strategy that exhibits promising potential for treating skin fibrosis., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This study utilised a cross-sectional survey design to assess the levels of knowledge and awareness among 841 undergraduate dental students from Saudi Arabia regarding sustainable development goals (SDGs) and sustainable dental practices (SDP)., Materials and Methods: A self-administered online questionnaire was distributed to adults aged between 18 and 35 years of both genders, from November 2022 to November 2023. The study has obtained appropriate ethical approval., Results: Participants exhibited a moderate level of knowledge and awareness regarding the SDGs, while demonstrating a high level of awareness specifically related to the SDP. The presence of a correlation between gender-associated beliefs and pro-environmental behaviours is apparent. Additionally, it has been observed that participants who engage in clinical activities exhibit a heightened level of awareness concerning SDP., Conclusions: By assessing dental students' current knowledge and awareness of the SDGs and SDP, we can inform stakeholders in the dental industry about how to enhance sustainability competence and develop dental policy curricula. This will better prepare students to serve as educators as well as professionals, aligning with their commitment to integrating the principles and objectives of various SDGs and SDP into dental education and practice., (© 2024. The Author(s).)

Colorectal cancer (CRC) is the third leading cause of cancer death in the U.S., and early detection and diagnosis are essential for effective treatment. Current methods are inadequate for rapid detection of early disease, revealing flat lesions, and delineating tumor margins with accuracy and molecular specificity. Fluorescence endoscopy can generate wide field-of-view images enabling detection of CRC lesions and margins; increased signal intensity and improved signal-to-noise ratios can increase both speed and sensitivity of cancer detection. For this purpose, we developed targeted near-infrared (NIR) fluorescent silica nanoparticles (FSNs). We tuned their size to 50-200 nm and conjugated their surface with an antibody to carcinoembryonic antigen (CEA) to prepare CEA-FSNs. The physicochemical properties and biodegradable profiles of CEA-FSN were characterized, and molecular targeting was verified in culture using HT29 (CEA positive) and HCT116 (CEA negative) cells. CEA-FSNs bound to the HT29 cells to a greater extent than to the HCT116 cells, and smaller CEA-FSNs were internalized into HT29 cells more efficiently than larger CEA-FSNs. After intravenous administration of CEA-FSNs, a significantly greater signal was observed from the CEA-positive HT29 than the CEA-negative HCT116 tumors in xenografted mice. In F344-PIRC rats, polyps in the intestine were detected by white-light endoscopy, and NIR fluorescent signals were found in the excised intestinal tissue after topical application of CEA-FSNs. Immunofluorescence imaging of excised tissue sections demonstrated that the particle signals coregistered with signals for both CRC and CEA. These results indicate that CEA-FSNs have potential as a molecular imaging marker for early diagnosis of CRC.

Recently, vast efforts towards sustainability have been made in the pharmaceutical industry. In conventional oil-in-water (O/W) cream formulations, various petroleum-based excipients, namely mineral oil and petrolatum, are commonly used. Natural or synthetic excipients, derived from vegetable sources, were explored as alternatives to petroleum-based excipients in prototype topical creams, with 1% (w/w) lidocaine. A conventional cream comprised of petroleum-derived excipients was compared to creams containing sustainable excipients in terms of key quality and performance attributes, physicochemical properties, and formulation performance. The petrolatum-based control formulation had the highest viscosity of 248.0 Pa·s, a melting point of 42.7°C, a low separation index at 25°C of 0.031, and an IVRT flux of 52.9 µg/cm 2 /h. Formulation SUS-4 was the least viscous formulation at 86.9 Pa·s, had the lowest melting point of 33.6°C, the highest separation index of 0.120, and the highest IVRT flux of 139.4 µg/cm 2 /h. Alternatively, SUS-5 had a higher viscosity of 131.3 Pa·s, a melting point of 43.6°C, a low separation index of 0.046, and the lowest IVRT flux of 25.2 µg/cm 2 /h. The cumulative drug permeation after 12 h from SUS-4, SUS-5, and the control were 126.2 µg/cm 2 , 113.8 µg/cm 2 , and 108.1 µg/cm 2 , respectively. The composition of the oil-in-water creams had influence on physicochemical properties and drug release; however, skin permeation was not impacted. Sustainable natural or synthetic excipients in topical cream formulations were found to be suitable alternatives to petroleum-based excipients with comparable key quality attributes and performance attributes and should be considered during formulation development., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Gastric cancer treatment is challenging due to the lack of early-stage diagnostic technology and targeted delivery systems. Currently, the available treatments for gastric cancer are surgery, chemotherapy, immunotherapy, and radiation. These strategies are either invasive or require systemic delivery, exerting toxicities within healthy tissues. By creation of a targeted delivery system to the stomach, gastric cancer can be treated in the early stages. Such an approach reduces the negative effects on the rest of the body by minimizing systemic absorbance and random localization. With this in mind, we developed a mucoadhesive vehicle composed of β- G lucan A nd D ocosahexaenoic A cid (GADA) for controlled drug/gene delivery. In the current study, we investigated the therapeutic effect of codelivery Bcl2 inhibitors navitoclax (NAVI) and siRNA (Bcl2) via oral using GADA. The therapeutic efficacy of the GADA-mediated oral NAVI/siRNA was investigated in a gastric cancer mouse model. Higher Bcl2 inhibition efficacy was observed in Western blotting and TUNEL assay in mice treated with GADA/NAVI/siRNA compared to free NAVI, siRNA, and NAVI/siRNA. Histology (H&E) and immunohistochemistry (Ki67, TUNEL, and BCl2) analyses confirmed a significant reduction of the tumor region. Interaction between GADA and mucus resulted in retention for over 6 h and thereby sustained local payload release. The developed oral carrier GADA is an emerging vehicle that has promising potential in oral delivery of both small and large molecules, and their mucoadhesive property results in improved therapeutic efficacy with minimal side effects compared to conventional treatment. This study opens a new window for the effective delivery of oral medicine for the treatment of gastric cancer and other gastrointestinal diseases.

Pulmonary fibrosis (PF) is a progressive, and life-threatening interstitial lung disease which causes scarring in the lung parenchyma and thereby affects architecture and functioning of lung. It is an irreversible damage to lung functioning which is related to epithelial cell injury, immense accumulation of immune cells and inflammatory cytokines, and irregular recruitment of extracellular matrix. The inflammatory cytokines trigger the differentiation of fibroblasts into activated fibroblasts, also known as myofibroblasts, which further increase the production and deposition of collagen at the injury sites in the lung. Despite the significant morbidity and mortality associated with PF, there is no available treatment that efficiently and effectively treats the disease by reversing their underlying pathologies. In recent years, many therapeutic regimens, for instance, rho kinase inhibitors, Smad signaling pathway inhibitors, p38, BCL-xL/ BCL-2 and JNK pathway inhibitors, have been found to be potent and effective in treating PF, in preclinical stages. However, due to non-selectivity and non-specificity, the therapeutic molecules also result in toxicity mediated severe side effects. Hence, this review demonstrates recent advances on PF pathology, mechanism and targets related to PF, development of various drug delivery systems based on small molecules, RNAs, oligonucleotides, peptides, antibodies, exosomes, and stem cells for the treatment of PF and the progress of various therapeutic treatments in clinical trials to advance PF treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Over the last decades, ionic liquids (IL) have shown great potential in non-invasive delivery starting from synthetic small molecules to biological large molecules. ILs are emerging as a particular class of drug delivery systems due to their unique physiochemical properties, simple surface modification, and functionalization. These features of IL help achieve specific design principles that are essential for a non-invasive drug delivery system. In this review, we have discussed IL and their applications in non-invasive drug delivery systems. We evaluated state-of-the-art development and advances of IL aiming to mitigate the biological and physical barriers to improve transdermal and oral delivery, summarized in this review. We also provided an overview of the various factors determining the systemic transportation of IL-based formulation. Additionally, we have emphasized how the ILs facilitate the transportation of therapeutic molecules by overcoming biological barriers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cardiac fibrosis is the excessive accumulation of extracellular matrix components in the heart, leading to reduced cardiac functionality and heart failure. This review provides an overview of the therapeutic applications of nanotechnology for the treatment of cardiac fibrosis. We first delve into the fundamental pathophysiology of cardiac fibrosis, highlighting the key molecular players, including Matrix Metalloproteinases, Transforming Growth Factor-beta, and several growth factors, cytokines, and signaling molecules. Each target presents a unique opportunity to develop targeted nano-therapies. We then focus on recent advancements in nanotechnology and how nanoparticles can be engineered to deliver drugs or therapeutic genes. These advanced delivery approaches have shown significant potential to inhibit fibrosis-promoting factors, thereby mitigating the fibrotic response and potentially reversing disease progression. In addition, we discuss the challenges associated with developing and translating nanotechnology-based drug delivery systems, including ensuring biocompatibility, safety, and regulatory compliance. This review highlights how nanotechnology can bridge the gap between lab research and clinical practice for treating cardiac fibrosis., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Interdisciplinary Medicine published by Wiley-VCH GmbH on behalf of Nanfang Hospital, Southern Medical University.)

Polyether ether ketone (PEEK) is a biocompatible polymer used in maxillofacial and orthopedic applications because of its mechanical properties and chemical stability. However, this biomaterial is inert and requires surface modification to make it bioactive, enhancing implant-tissue integration and giving the material the ability to interact with the surrounding microenvironment. In this paper, surface of PEEK was activated by oxygen plasma treatment and this resulted in increasing reactivity and surface hydrophilicity. Then, a polydopamine (PDA) coating was deposited over the surface followed by biofunctionalization with an RGD peptide. The plasma effect was studied by contact angle measurements and scanning electron microscopy. X-ray photoelectron spectroscopy confirmed the presence of PDA coating and RGD peptide. Crystallinity and phase identification were carried out through X-ray diffraction. Quantification of the immobilized peptide over the PEEK surface was reached through UV-vis spectroscopy. In addition, in vitro tests with fibroblast cell line (NIH/3T3) determined the viability, attachment, spreading, and proliferation of these cells over the modified PEEK surfaces. According to the results, PEEK surfaces functionalized with peptides demonstrated an increased cellular response with each successive surface modification.

Cancer is a major health concern worldwide and is still in a continuous surge of seeking for effective treatments. Since the discovery of RNAi and their mechanism of action, it has shown promises in targeted therapy for various diseases including cancer. The ability of RNAi to selectively silence the carcinogenic gene makes them ideal as cancer therapeutics. Oral delivery is the ideal route of administration of drug administration because of its patients' compliance and convenience. However, orally administered RNAi, for instance, siRNA, must cross various extracellular and intracellular biological barriers before it reaches the site of action. It is very challenging and important to keep the siRNA stable until they reach to the targeted site. Harsh pH, thick mucus layer, and nuclease enzyme prevent siRNA to diffuse through the intestinal wall and thereby induce a therapeutic effect. After entering the cell, siRNA is subjected to lysosomal degradation. Over the years, various approaches have been taken into consideration to overcome these challenges for oral RNAi delivery. Therefore, understanding the challenges and recent development is crucial to offer a novel and advanced approach for oral RNAi delivery. Herein, we have summarized the delivery strategies for oral delivery RNAi and recent advancement towards the preclinical stages., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Solid tumors are abnormal mass of tissue, which affects the organs based on its malignancy and leads to the dysfunction of the affected organs. The major problem associated with treatment of solid tumors is delivering anticancer therapeutics to the deepest layers/core of the solid tumor. Deposition of excessive extracellular matrix (ECM) hinders the therapeutics to travel towards the core of the tumor. Therefore, conventional anticancer therapeutics can only reduce the tumor size and that also for a limited duration, and tumor recurrence occurs once the therapy is discontinued. Additionally, by the time the cancer is diagnosed, the cancer cells already started affecting the major organs of the body such as lung, liver, spleen, kidney, and brain, due to their ability to metastasize and lung is the primary site for them to be infiltrated. To facilitate the anticancer therapeutics to penetrate the deeper layers of tumor, and to provide concurrent treatment of both the solid tumor and metastasis, we have designed and developed a Bimodal Light Assisted Skin Tumor and Metastasis Treatment (BLAST), which is a combination of photothermal and chemotherapeutic moieties. The BLAST is composed of 2D boron nitride (BN) nanosheet with adsorbed molecules of BCL-2 inhibitor, Navitoclax (NAVI) on its surface, that can breakdown excessive ECM network and thereby facilitate dissociation of the solid tumor. The developed BLAST was evaluated for its ability to penetrate solid tumors using 3D spheroids for the uptake, cytotoxicity, growth inhibition, reactive oxygen species (ROS) detection, penetration, and downregulation of proteins upon laser irradiation. The in vivo therapeutic studies on a skin cancer mice model revealed that the BLAST with and without laser were able to penetrate the solid tumor, reduce tumor volume in mice, dissociate the protein network, and prevent lung metastasis as confirmed by immunohistochemistry and western blot analysis. Post analysis of serum and blood components revealed the safety and efficacy of BLAST in mice. Hence, the developed BLAST holds strong promise in solid tumor treatment and metastasis prevention simultaneously., Competing Interests: Declaration of Competing Interest Md Nurunnabi serves as Scientific Advisory Board member for KB BioMed Inc., and Filament LLC (Dunatech), and owns equity for DunaTech LLC. Md Nurunnabi and Himanshu Bhatt is an inventor on patents related to the tools and methods reported in this manuscript (owned and managed by University of Texas at El Paso)., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Magnetic particle imaging (MPI) is an emerging imaging modality that provides direct and quantitative mapping of iron oxide tracers. To achieve high sensitivity and good spatial resolution images, a magnetic nanoparticle with a higher contrast intensity needs to be developed. Currently, a majority of MPIs being developed for potential clinical application are composed of iron oxide nanoparticles with a spherical shape. In this project, we intend to report development of high-performance carbon (C) coated iron-cobalt (FeCo) nanoparticles (FeCo/C) and investigate their feasibility as a MPI agent. We have synthesized FeCo/C through a facile and simple method at mild temperature that is safe, easy, and up-scalable. We studied the structural and functional relationships and biocompatibility of this MPI agent in vitro. However, to enhance the aqueous solubility and biocompatibility, the surface of FeCo/C was modified with polyethylene glycol (PEG). We found that variation in the ratio of Fe and Co plays a vital role in their physical properties and functionality. In vitro imaging confirms that the Fe 3 Co 1 /C nanoparticle has highly competitive MPI intensity compared to VivoTrax, a commercially available MPI agent. Confocal laser scanning microscopy imaging with Rhodamine B labeled FeCo/C displays cellular internalization by the A375 cancer cells. The in vitro toxicity analysis concludes that there is no significant toxicity of FeCo/C nanoparticles. Therefore, the newly developed MPI agent holds strong promise for biomedical imaging and could be further validated in vivo in small animals.

Based on cancer-related deaths, stomach cancer is ranked fifth, and first among Hispanics. Lack of technologies for early diagnosis and unavailability of target-specific therapeutics are largely the causes of the poor therapeutic outcomes from existing chemotherapeutics. Currently available therapeutic modalities are invasive and require systemic delivery, although the cancer is localized in the stomach at its early stage. Therefore, we hypothesize that an oral local delivery approach can extend the retention duration of the therapeutics modalities within the stomach and thereby enhance therapeutic efficacy. To accomplish this, we have developed a ß-glucan (BG)-based oral delivery vehicle that can adhere to the mucus lining of the stomach for an extended period while controlling the release of Bcl2 siRNA and 5-fluorouracil (5FU) payload for over 6 h. We found that Bcl2 siRNA selectively knocked down the Bcl2 gene in a C57BL/6 stomach cancer mouse model followed by upregulation of apoptosis and remission of cancer. BG was found to be very effective in maintaining the stability of siRNA for at least 6 h, when submerged in simulated gastric juice tested in vitro. To investigate the potential therapeutic effects in vivo, we used a stomach cancer mouse model, where C57BL/6 mice were treated with 5FU, BG/5FU, siRNA, BG/siRNA, and BG/5FU/siRNA. Higher inhibition of Bcl2 and therapeutic efficacy were observed in mice treated with BG/5FU/siRNA confirmed with Western blotting and a TUNEL assay. Significant reduction in the tumor region was observed with histology (H&E) and immunohistochemistry (Ki67, TUNEL, and Bcl2) analyses. Overall, the oral formulation shows improved efficacy with nonsignificant side effects compared to the conventional treatment tested in the gastric cancer mouse model.

Obesity is a complex disorder associated with immense health consequences including high risk of cardiovascular diseases, diabetes, and cancer. Abnormality in the thyroid gland, genetics, less physical activity, uptake of excessive diet, and leptin resistance are critical factors in the development of obesity. To determine the treatment strategy, understanding the pathophysiology of obesity is crucial. For instances, leptin resistance mediated obesity defined by the presence of excessive leptin hormone (Lep) in the systemic circulation is very common in diet induced obesity. Therefore, our hypothesis is that quantitative measurement of Lep from blood can help to identify individuals with Lep resistant mediated obesity and thereby guide toward a proper treatment strategy. In this work, we aim to utilize an electrochemical immunosensing platform for diagnosis of obesity by measuring the Lep content in systemic circulation. A porous carbon confined FeNi bimetallic system was synthesized with three different ratios of Fe and Ni ions using high temperature pyrolysis technique. The suitability of the sensor for detecting Lep was studied using both CV and EIS techniques. The limit of detection (LOD) for GCE was recorded as 157.4 fg/mL with a wide linear concentration range of 500 fg/mL to 80 ng/mL, while for SPCE the LOD was 184.9 fg/mL with a linear range of 500 fg/mL to 50 ng/mL. Finally, the feasibility and applicability of the sensor for Lep detection was tested with serum collected from high fat diet induced obese rats. The selectivity, sensitivity, storage, and experimental stability and reproducibility tests showed potential for this biosensor platform as a point-of-care Lep detection device.