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(1) Background: Many drugs possess poor bioavailability, and many strategies are available to overcome this issue. In this study, smartFilm technology, i.e., a porous cellulose matrix (paper), in which the active compound can be loaded onto in an amorphous state was utilised for oral administration to improve the solubility and bioactivity of a poorly soluble BSC class IV antibiotic. (2) Methods: Norfloxacin was used as the model drug and loaded into commercially available paper. The resulting norfloxacin-loaded smartFilms were transformed into smartFilm granules via wet granulation and the resulting norfloxacin-loaded smartFilm granules were transformed into norfloxacin-loaded tablets made from paper, i.e., smartFilm tablets. The crystalline state of norfloxacin was investigated, as well as the pharmaceutical properties of the granules and the tablets. The bioactivity of the smartFilm tablets was assessed in vitro and ex vivo to determine the antibacterial activity of norfloxacin. The results were compared to a physical mixture tablet that contained non-loaded paper granules and equal amounts of norfloxacin as a crystalline powder. (3) Results: Norfloxacin-loaded smartFilm granules and norfloxacin-loaded smartFilm tablets contained norfloxacin in an amorphous state, which resulted in an improved and faster release of norfloxacin when compared to the physical mixture tablet. The bioactivity was up to three times higher when compared to the physical mixture tablet. The ex vivo model was demonstrated to be a useful tool that allows for a fast and cost-effective discrimination between "good" and "bad" formulations. It provides realistic physiological conditions and can therefore yield meaningful, additional biopharmaceutical information that cannot be assessed in classical in vitro experiments. (4) Conclusions: smartFilm tablets are a promising, universal, industrially feasible and cost-effective formulation strategy for improved solubility and enhanced bioactivity of poorly soluble drugs. [ABSTRACT FROM AUTHOR]

Improved global access to novel age‐appropriate formulations for paediatric subsets, either of new chemical entities or existing drugs, is a priority to ensure that medicines meet the needs of these patients. However, despite regulatory incentives, the introduction to the market of paediatric formulations still lags behind adult products. This is mainly caused by additional complexities associated with the development of acceptable age‐appropriate paediatric medicines. This position paper recommends the use of a paediatric Quality Target Product Profile as an efficient tool to facilitate early planning and decision making across all teams involved in paediatric formulation development during the children‐centric formulation design for new chemical entities, or to repurpose/reformulate off‐patent drugs. Essential key attributes of a paediatric formulation are suggested and described. Moreover, greater collaboration between formulation experts and clinical colleagues, including healthcare professionals, is advocated to lead to safe and effective, age‐appropriate medicinal products. Acceptability testing should be a secondary endpoint in paediatric clinical trials to ensure postmarketing adherence is not compromised by a lack of acceptability. Not knowing the indications and the related age groups and potential dosing regimens early enough is still a major hurdle for efficient paediatric formulation development; however, the proposed paediatric Quality Target Product Profile could be a valuable collaborative tool for planning and decision making to expedite paediatric product development, particularly for those with limited experience in developing a paediatric product. [ABSTRACT FROM AUTHOR]

Paper‐based electronics are emerging as a new class of technology with broad areas of application. Despite several efforts to fabricate new types of flexible electronic devices by screen printing of conductive paste, many of them are often nonbiodegradable, toxic, and expensive, limiting their practical use in bioresorbable paper‐based electronics. To address this need, a highly conductive and biodegradable bimodal conductive paste is developed using cost‐effective zinc‐based micro and nanoparticles with a facile low‐temperature sintering process compatible with paper substrates. The two‐step sintering process involves the removal of the insulating zinc oxide layer by spray coating acetic acid followed by a heat press sintering process to ensure the formation of highly packed and continuous metallic traces. The required conditions for the heat press sintering process are systematically studied using electrical, optical, and mechanical characterization techniques. The results of these investigations revealed an ultra‐packed microstructure with high electrical conductivity (0.5 × 105 S m−1) and low oxide content that is obtained with a heat press sintering setting of 220 °C for 60 s. Finally, as a proof of concept, the conductive paste with an optimized sintering process is used to fabricate a wearable wireless heater for remote‐controlled release of therapeutics. The controlled delivery of the system is validated in the practical and on‐demand delivery of antibiotics for eradicating commonly found bacteria such as Staphylococcus aureus in dermal wound infections. The biocompatibility of all the materials and manufacturing process is validated by NIH/3T3 fibroblast cells via MTT assay and live/dead staining. [ABSTRACT FROM AUTHOR]

Older people are often affected by impaired organ and bodily functions resulting in multimorbidity and polypharmacy, turning them into the main user group of many medicines. Very often, medicines have not specifically been developed for older people, causing practical medication problems for them like limited availability of easy to swallow formulations, easy to open packaging and dosing instructions for enteral administration. In 2020, the European Medicines Agency (EMA) published a reflection paper 'Pharmaceutical development of medicines for use in the older population', which discusses how the emerging needs of an ageing European population can be addressed by medicines regulation. The paper intends to help industry to better consider the needs of older people during pharmaceutical/clinical medicines development by summarising data on the most relevant topics, providing early suggestions on how to move forward and prompting expert discussions and studies into knowledge gaps. Topics include patient acceptability, (dis)advantages of an administration route, formulation, dosage form, packaging, dosing device and user instruction. While the paper is directed at older people and the pharmaceutical industry, the reflections are also relevant to younger patients with similar disease‐related needs and of value to other stakeholders parties, e.g., healthcare professionals, academics, patients and caregivers, as the paper makes clear what can be expected from industry and where collaborative work is needed. This commentary provides an overview of the different steps in the development of the reflection paper, discusses points considered most controversial and/or subject to (multidisciplinary) expert discussions and indicates their value for real world clinical practice. [ABSTRACT FROM AUTHOR]

Paper is a common material that is promising for constructing microfluidic chips (lab-on-a-paper) for diagnostics and drug delivery for biomedical applications. In the past decade, extensive research on paper-based microfluidics has accumulated a large number of scientific publications in the fields of biomedical diagnosis, food safety, environmental health, drug screening and delivery. This review focuses on the recent progress on paper-based microfluidic technology with an emphasis on the design, optimization and application of the technology platform, in particular for medical diagnostics and drug delivery. Novel advances have concentrated on engineering paper devices for point-of-care (POC) diagnostics, which could be integrated with nucleic acid-based tests and isothermal amplification experiments, enabling rapid sample-to-answer assays for field testing. Among the isothermal amplification experiments, loop-mediated isothermal amplification (LAMP), an extremely sensitive nucleic acid test, specifically identifies ultralow concentrations of DNA/RNA from practical samples for diagnosing diseases. We thus mainly focus on the paper device-based LAMP assay for the rapid infectious disease diagnosis, foodborne pathogen analysis, veterinary diagnosis, plant diagnosis, and environmental public health evaluation. We also outlined progress on paper microfluidic devices for drug delivery. The paper concludes with a discussion on the challenges of this technology and our insights into how to advance science and technology towards the development of fully functional paper devices in diagnostics and drug delivery. Unlabelled Image [ABSTRACT FROM AUTHOR]

Paper devices have many advantages over other microfluidic devices. The paper substrate, from cellulose to glass fiber, is an inexpensive substrate that can be readily modified to suit a variety of applications. Milli- to micro-scale patterns can be designed to create a fast, cost-effective device that uses small amounts of reagents and samples. Finally, well-established chemical and biological methods can be adapted to paper to yield a portable device that can be used in resource-limited areas (e.g., field work). Altogether, the paper devices have grown into reliable analytical devices for screening low quality pharmaceuticals. This review article presents fabrication processes, detection techniques, and applications of paper microfluidic devices toward pharmaceutical screening. [ABSTRACT FROM AUTHOR]

This paper explores the latest advancements in aerogel technology for antimicrobial therapy, revealing their interesting capacity that could improve the current medical approaches for antimicrobial treatments. Aerogels are attractive matrices because they can have an antimicrobial effect on their own, but they can also provide efficient delivery of antimicrobial compounds. Their interesting properties, such as high porosity, ultra-lightweight, and large surface area, make them suitable for such applications. The fundamentals of aerogels and mechanisms of action are discussed. The paper also highlights aerogels' importance in addressing current pressing challenges related to infection management, like the limited drug delivery alternatives and growing resistance to antimicrobial agents. It also covers the potential applications of aerogels in antimicrobial therapy and their possible limitations. [ABSTRACT FROM AUTHOR]

In recent years, polymer-supported magnetic iron oxide nanoparticles (MIO-NPs) have gained a lot of attention in biomedical and healthcare applications due to their unique magnetic properties, low toxicity, cost-effectiveness, biocompatibility, and biodegradability. In this study, waste tissue papers (WTP) and sugarcane bagasse (SCB) were utilized to prepare magnetic iron oxide (MIO)-incorporated WTP/MIO and SCB/MIO nanocomposite particles (NCPs) based on in situ co-precipitation methods, and they were characterized using advanced spectroscopic techniques. In addition, their anti-oxidant and drug-delivery properties were investigated. Field emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD) analyses revealed that the shapes of the MIO-NPs, SCB/MIO-NCPs, and WTP/MIO-NCPs were agglomerated and irregularly spherical with a crystallite size of 12.38 nm, 10.85 nm, and 11.47 nm, respectively. Vibrational sample magnetometry (VSM) analysis showed that both the NPs and the NCPs were paramagnetic. The free radical scavenging assay ascertained that the WTP/MIO-NCPs, SCB/MIO-NCPs, and MIO-NPs exhibited almost negligible antioxidant activity in comparison to ascorbic acid. The swelling capacities of the SCB/MIO-NCPs and WTP/MIO-NCPs were 155.0% and 159.5%, respectively, which were much higher than the swelling efficiencies of cellulose-SCB (58.3%) and cellulose-WTP (61.6%). The order of metronidazole drug loading after 3 days was: cellulose-SCB < cellulose-WTP < MIO-NPs < SCB/MIO-NCPs < WTP/MIO-NCPs, whereas the sequence of the drug-releasing rate after 240 min was: WTP/MIO-NCPs < SCB/MIO-NCPs < MIO-NPs < cellulose-WTP < cellulose-SCB. Overall, the results of this study showed that the incorporation of MIO-NPs in the cellulose matrix increased the swelling capacity, drug-loading capacity, and drug-releasing time. Therefore, cellulose/MIO-NCPs obtained from waste materials such as SCB and WTP can be used as a potential vehicle for medical applications, especially in a metronidazole drug delivery system. [ABSTRACT FROM AUTHOR]

• Cyclodextrins, polyvinylpyrrolidone, polyvinyl acetate and polyethylene glycol increase probucol solubility. • Probucol based microparticles can be dispersed in aqueous solutions, allowing for slow probucol release from the particulate matrix. • Ursodeoxycholic acid stabilises probucol microparticles and delays probucol release. • Probucol based microparticles show no cytotoxicity in permissive HEI-OC1 cells. • Ursodeoxycholic acid in combination with probucol enhances probucol's protective effects in vitro against cisplatin. Targeted drug delivery is an ongoing aspect of scientific research that is expanding through the design of micro- and nanoparticles. In this paper, we focus on spray dried microparticles as carriers for a repurposed lipophilic antioxidant (probucol). We characterise the microparticles and quantify probucol prior to assessing cytotoxicity on both control and cisplatin treated hair cells (known as House Ear Institute-Organ of Corti 1; HEI-OC1). The addition of water-soluble polymers to 2% β -cyclodextrin resulted in a stable probucol formulation. Ursodeoxycholic acid (UDCA) used as formulation excipient increases probucol miscibility and microparticle drug content. Formulation characterisations reveals spray drying results in spherical UDCA-drug microparticles with a mean size distribution of ∼5–12 μm. Probucol microparticles show stable short-term storage conditions accounting for only ∼10% loss over seven days. By mimicking cell culture conditions, both UDCA-probucol (67%) and probucol only (82%) microparticles show drug release in the initial two hours. Furthermore, probucol formulations with or without UDCA preserve cell viability and reduce cisplatin-induced oxidative stress. Mitochondrial bioenergetics results in lower basal respiration and non-mitochondrial respiration, with higher maximal respiration, spare capacity, ATP production and proton leak within cisplatin challenged UDCA-probucol groups. Overall, we present a facile method for incorporating lipophilic antioxidant carriers in polymer-based particles that are tolerated by HEI-OC1 cells and show stable drug release, sufficient in reducing cisplatin-induced reactive oxygen species accumulation. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small, non-coding RNAs that play a crucial role in regulating gene expression. Dysfunction in miRNAs can lead to various diseases, including cancers, neurological disorders, and cardiovascular conditions. To date, approximately 2000 miRNAs have been identified in humans. These small molecules have shown promise as disease biomarkers and potential therapeutic targets. Therefore, identifying miRNA biomarkers for diseases and developing effective miRNA drug delivery systems are essential. Nanotechnology offers promising new approaches to addressing scientific and medical challenges. Traditional miRNA detection methods include next-generation sequencing, microarrays, Northern blotting, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Nanotechnology can serve as an effective alternative to Northern blotting and RT-qPCR for miRNA detection. Moreover, nanomaterials exhibit unique properties that differ from larger counterparts, enabling miRNA therapeutics to more effectively enter target cells, reduce degradation in the bloodstream, and be released in specific tissues or cells. This paper reviews the application of nanotechnology in miRNA detection and drug delivery systems. Given that miRNA therapeutics are still in the developing stages, nanotechnology holds great promise for accelerating miRNA therapeutics development. [ABSTRACT FROM AUTHOR]

Hydrogels are formed of crosslinked polymer chains arranged in three-dimensional (3D) networks. These chains have good water-containing capacity and are soft and malleable. Hydrogels have good biocompatibility due to their significant water content, flexible structure, and numerous holes. These characteristics make them analogous to biological tissues. Despite the publication of 8700 literature related to hydrogel biomedical applications in the past 52 years (1973 ~ 2024), studies on the use of hydrogels in biomedicine are few. To gain a comprehensive understanding of their current development status, research trends, and prospects in the biomedical application field, it is imperative to conduct a thorough retrospective analysis. In this study, we employ bibliometric analysis and CiteSpace software to quantitatively and visually analyze articles published in this field. Firstly, we provide a quantitative analysis of authorship and institutional publications over the past 52 years to elucidate the fundamental development status regarding hydrogel biomedical applications. Secondly, we did visual studies on terms that are high-frequency, explosive, keyword clustering, and so on, to understand the directionality and evolution of the main research hotspots during each period. Notably, our findings emphasize that fabricating hydrogels into wound healing-promoting dressings emerges as a prominent hotspot within the application field. We anticipate that this paper will inspire researchers with novel ideas for advancing hydrogel applications in biomedicine. [ABSTRACT FROM AUTHOR]

This paper reviews the latest trends and applications of silicone in ophthalmology, especially related to intraocular lenses (IOLs). Silicone, or siloxane elastomer, as a synthetic polymer, has excellent biocompatibility, high chemical inertness, and hydrophobicity, enabling wide biomedical applications. The physicochemical properties of silicone are reviewed. A review of methods for mechanical and in vivo characterization of IOLs is presented as a prospective research area, since there are only a few available technologies, even though these properties are vital to ensure medical safety and suitability for clinical use, especially if long-term function is considered. IOLs represent permanent implants to replace the natural lens or for correcting vision, with the first commercial foldable lens made of silicone. Biological aspects of posterior capsular opacification have been reviewed, including the effects of the implanted silicone IOL. However, certain issues with silicone IOLs are still challenging and some conditions can prevent its application in all patients. The latest trends in nanotechnology solutions have been reviewed. Surface modifications of silicone IOLs are an efficient approach to further improve biocompatibility or to enable drug-eluting function. Different surface modifications, including coatings, can provide long-term treatments for various medical conditions or medical diagnoses through the incorporation of sensory functions. It is essential that IOL optical characteristics remain unchanged in case of drug incorporation and the application of nanoparticles can enable it. However, clinical trials related to these advanced technologies are still missing, thus preventing their clinical applications at this moment. [ABSTRACT FROM AUTHOR]

In the present paper the polyelectrolyte multilayers (PEMs) deposited on lyophilized composite polylactic acid / poly(e-caprolactone) substrates were investigated. The substrates were charged under positive corona discharge for 1 min with 5 kV voltage applied to the corona electrode and 1 kV voltage of the same polarity applied to the grid. The dependences on the time of storage of the normalized surface potential of the charged substrates (positive) were investigated. Solutions of 1 % casein in phosphate buffer (pH 8) and 0.1 % chitosan in acetate buffer (pH 5) with added benzydamine hydrochloride were prepared. The creation of the multilayers was carried out by utilizing the technique Layer-by-Layer (LbL). The first built-up layer always possesses an electric charge opposite to that of the substrate. The loading efficiency and drug release kinetics of the chosen model drug were carried out spectrophotometrically. [ABSTRACT FROM AUTHOR]

In recent years, there has been a notable surge in the utilization of stabilized bile acid liposomes, chemical conjugates, complexes, mixed micelles, and other drug delivery systems derived from bile acids, often referred to as bilosomes. The molecular structure and interactions of these amphiphilic compounds provide a distinctive and captivating subject for investigation. The enhanced stability of new generation bilosomes inside the gastrointestinal system results in the prevention of drug degradation and an improvement in mucosal penetration. These characteristics render bilosomes to be a prospective nanocarrier for pharmaceutical administration, prompting researchers to investigate their potential in other domains. This review paper discusses bilosomes that have emerged as a viable modality in the realm of drug delivery and have significant promise for use across several domains. Moreover, this underscores the need for additional investigation and advancement in order to comprehensively comprehend the prospective uses of bilosomes and their effectiveness in the field of pharmaceutical administration. This review study explores the current scholarly attention on bilosomes as prospective carriers for drug delivery. Therapeutic areas where bilosomes have shown outstanding performance in terms of drug delivery are outlined in the graphical abstract. [ABSTRACT FROM AUTHOR]

Organic–inorganic hybrids represent a good solution to improve the solubility and dissolution rates of poorly soluble drugs whose number has been increasing in the last few years. One of the most diffused inorganic matrices is hydroxyapatite (HAP), which is a biocompatible and osteoconductive material. However, the understanding of the hybrids' functioning mechanisms is in many cases limited; thus, thorough physicochemical characterizations are needed. In the present paper, we prepared hybrids of pure and Mg-doped hydroxyapatite with meloxicam, a drug pertaining to the Biopharmaceutical Classification System (BCS) class II, i.e., drugs with low solubility and high permeability. The hybrids' formation was demonstrated by FT-IR, which suggested electrostatic interactions between HAP and drug. The substitution of Mg in the HAP structure mainly produced a structural disorder and a reduction in crystallite sizes. The surface area of HAP increased after Mg doping from 82 to 103 m2g−1 as well as the pore volume, justifying the slightly high drug amount adsorbed by the Mg hybrid. Notwithstanding the low drug loading on the hybrids, the solubility, dissolution profiles and wettability markedly improved with respect to the drug alone, particularly for the Mg doped one, which was probably due to the main distribution of the drug on the HAP surface. [ABSTRACT FROM AUTHOR]

Sarcopenia is a prevalent degenerative skeletal muscle condition in the elderly population, posing a tremendous burden on diseased individuals and healthcare systems worldwide. Conventionally, sarcopenia is currently managed through nutritional interventions, physical therapy, and lifestyle modification, with no pharmaceutical agents being approved for specific use in this disease. As the pathogenesis of sarcopenia is still poorly understood and there is no treatment recognized as universally effective, recent research efforts have been directed at better comprehending this illness and diversifying treatment strategies. In this respect, this paper overviews the new advances in sarcopenia treatment in correlation with its underlying mechanisms. Specifically, this review creates an updated framework for sarcopenia, describing its etiology, pathogenesis, risk factors, and conventional treatments, further discussing emerging therapeutic approaches like new drug formulations, drug delivery systems, stem cell therapies, and tissue-engineered scaffolds in more detail. [ABSTRACT FROM AUTHOR]

Many people lose their lives to cancer each year. The prevalence of illnesses, metabolic disorders, high-risk infections, and other conditions has been greatly slowed down by expanding scientific research. Chemotherapy and radiation are still the initial lines of treatment for cancer patients, along with surgical removal of tumors. Modifications have been made in chemotherapy since medicines frequently have substantial systemic toxicity and poor pharmacokinetics and still do not reach the tumor site at effective concentrations. Chemotherapy may now be administered more safely and effectively thanks to nanotechnology. Nanotechnology-based graphene quantum dots (GQDs) are very applicable in breast cancer detection, as a drug delivery system, and in the treatment of breast cancer because of their physical and chemical properties, lower toxicity, small size, fluorescence, and effective drug delivery. This paper analyzes the GQDs as cutting-edge platforms for biotechnology and nanomedicine also its application in drug delivery in cancer. It shows that GQDs can be effectively conjugated with hyaluronic acid (HA) to achieve efficient and target-specific delivery. [ABSTRACT FROM AUTHOR]

This paper concerns the aptitudes of medical staff to explore new therapies and training exercises for image-assisted robotic diligent interventions. This exploration can be carried out using physical, digital, or both copies of patients. Such physical and digital phantoms should approximate real living tissues through realistic biological properties. Such a realistic assessment could be achieved through strategies to reduce physical and numerical uncertainties. The concept of physical-virtual matched pairs is used in image-assisted robotic interventions to enable such reduction. The present commentary aimed to analyze and illustrate possibilities for increasing the capabilities of medical personnel to explore new therapies and training exercises for image-assisted robotic diligent interventions. In this context, the manuscript focused on the use of the physical-virtual digital twin (DT) concept to monitor image-assisted robotic interventions, thereby reducing the complexity and uncertainties involved in such a procedure. Extensions involve robotic operations assisted by human-in-the-loop DT, artificial intelligence (AI), and augmented reality (AR). The various topics covered in this commentary are supported by a review of the literature. [ABSTRACT FROM AUTHOR]

Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous topical administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts. Moreover, it provides data suggesting that the topical administration of melatonin as eye drops is a real possibility, utilizing nanotechnological formulations that could improve its solubility and permeation through the eye. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects. [ABSTRACT FROM AUTHOR]

Simple Summary: This review mainly focuses on epigenetic changes in a few selective genes associated with insulin insensitivity in the periphery and how this peripheral insulin insensitivity is linked with impaired signaling of insulin in the brain, thus causing Alzheimer's disease. DNA methylation and histone modifications are the focus of this review, with primary importance given to DNA methylation. Moreover, there has been a focus shift from the amyloid β hypothesis to epigenetic mechanisms. Furthermore, we discuss the advanced drug delivery systems that can be used for the delivery of drugs targeting the brain during Alzheimer's disease. The advanced drug delivery systems discussed in this paper are nanoparticles, vesicular systems, network systems and dendrimers, hydrogel-based systems, and biologics. Alzheimer's disease (AD) is a neurodegenerative condition that predominantly affects the hippocampus and the entorhinal complex, leading to memory lapse and cognitive impairment. This can have a negative impact on an individual's behavior, speech, and ability to navigate their surroundings. AD is one of the principal causes of dementia. One of the most accepted theories in AD, the amyloid β (Aβ) hypothesis, assumes that the buildup of the peptide Aβ is the root cause of AD. Impaired insulin signaling in the periphery and central nervous system has been considered to have an effect on the pathophysiology of AD. Further, researchers have shifted their focus to epigenetic mechanisms that are responsible for dysregulating major biochemical pathways and intracellular signaling processes responsible for directly or indirectly causing AD. The prime epigenetic mechanisms encompass DNA methylation, histone modifications, and non-coding RNA, and are majorly responsible for impairing insulin signaling both centrally and peripherally, thus leading to AD. In this review, we provide insights into the major epigenetic mechanisms involved in causing AD, such as DNA methylation and histone deacetylation. We decipher how the mechanisms alter peripheral insulin signaling and brain insulin signaling, leading to AD pathophysiology. In addition, this review also discusses the need for newer drug delivery systems for the targeted delivery of epigenetic drugs and explores targeted drug delivery systems such as nanoparticles, vesicular systems, networks, and other nano formulations in AD. Further, this review also sheds light on the future approaches used for epigenetic drug delivery. [ABSTRACT FROM AUTHOR]

Microneedles (MNs), renowned for their painless and minimally invasive qualities, exhibit significant potential for facilitating effective drug delivery, vaccination, and targeted sample extraction. Extracellular vesicles (EVs), serving as cargo for MNs, are naturally occurring nanovesicles secreted by cells and characterized by novel biomarkers, low immunogenicity, and cell-source-specific traits. MNs prove instrumental in extracting EVs from the sample fluid, thereby facilitating a promising diagnostic and prognostic tool. To harness the therapeutic potential of EVs in tissue repair, MNs with sustained delivery of EVs leverage micron-sized channels to enhance targeted site concentration, demonstrating efficacy in treating various diseases, such as Achillea tendinopathy, hair loss, spinal cord injury, and diabetic ulcers. EV-loaded MNs emerge as a promising platform for repair applications of skin, cardiac, tendon, hair, and spinal cord tissues. This review commences with an overview of MNs, subsequently delving into the role of EVs as cargo for MNs. The paper then synthesizes the latest advancements in the use of EV-loaded MNs for tissue regenerative repair, extending to research progress in extracting EVs from MNs for disease diagnosis and prognostic evaluations. It aims to offer valuable insights and forecast future research trajectories with the hope of inspiring innovative ideas among researchers in this field. [ABSTRACT FROM AUTHOR]

Carbon quantum dots (CQDs) represent a novel class of nanomaterials with uniquely interesting spectroscopic and dimensional features. Owing to their general low toxicity, they are preferred for application in drug delivery. Newer CQDs are plausible by substituting metal elements that impart new characteristics. This paper presents a novel dysprosium-doped CQD nanomaterial made as a composite with a β-cyclodextrin–polyethylene glycol–folate polymer. The synthesized material is characterized using X-ray diffraction, transmission electron microscopy, X-ray photoelectron and IR spectroscopies. The amount of polymer in the composite is investigated using thermogravimetric analysis. The size of the polymer-containing CQDS is around 8 nm. The dysprosium doping makes them magnetic in nature. Further, the material shows a broad absorption with the tail absorbance extending up to the near-infrared wavelength region. The designed nanocarrier shows a high camptothecin encapsulation efficiency of 91.03%. The in vitro anticancer studies on MCF-7 cells are carried out, and the IC50 value is more significant than the free carrier, implying a combined effect of the nanocarrier and the drug in action against the breast cancer cell lines. [ABSTRACT FROM AUTHOR]

In the past few decades, many researchers have focused their research interests on nanocomposite hydrogel fibers (NHFs). These practitioners have developed and optimized techniques for preparing nanofiber membranes such as the template method, microfluidic spinning, electrospinning, wet spinning and three-dimensional printing (3D printing). NHFs have important applications in wearable monitoring, diagnosis and nursing due to their various excellent properties (such as high-water content, porous morphology, flexibility, braiding and rich active functional groups). In this paper, the latest progress of NHFs in pose monitoring, continuous monitoring of physiological indicators, diagnosis, wearables, nursing, drug delivery and dressings are reviewed. This paper also aims to review their key operational parameters, advantages and disadvantages of NHFs in the above fields, including sensitivity, working range and other special properties. Specifically, NHFs can be used for continuous monitoring of biological postures (such as gestures) or physiological indicators (such as blood sugar) in vitro and in vivo. NHFs also can be used for long-term monitoring of related indicators in the wearable field. NHFs can be used in tissue engineering and drug delivery. Finally, we look forward to the development prospects, challenges and opportunities of the next generation of NHFs. We confirm that the emergence of NHFs in the field of diagnosis and treatment has opened up a new vision for human health. Researchers have optimized the template method, microfluidic spinning, electrospinning, wet spinning and 3D printing. [ABSTRACT FROM AUTHOR]

Extracellular Vesicles (EVs) encompasses a diverse array of vesicles generated by cells, with exosomes constituting the most prominent subset within this classification. Exosomes facilitate intercellular communication by transporting various biologics derived from donor or parental cells and delivering them to recipient cells. The potential of their distinctive ability to transport cargo has recently been investigated for its application to provide anti-cancer medications and imaging agents. Exosomes, which are endogenously generated, possess numerous advantages compared to the presently employed synthetic lipid-based nanoparticles for clinical applications in cancer treatment and other medical conditions. Identifying exosomes' involvement in human diseases has prompted extensive preclinical and clinical investigations into their potential as a viable means of Drug Delivery (DD) and as a theranostic tool for cancer diagnosis and treatment. Nevertheless, it is crucial to acknowledge that exosomes possess certain limitations, with one of the primary concerns revolving around the choice of the biological source utilized to generate exosomes that are both highly biocompatible and capable of being produced in large quantities. This paper examines the diverse origins of medically feasible exosomes that can be extracted to serve as drug carriers in the context of cancer therapy. The synthesis of nanosomes for anti-cancer DD has been presented in this paper. Nanosomes have been obtained by integrating Doxorubicin-conjugated Gold Nanoparticles (DOX-GNP) and organic exosomes. The precise delivery of "armed" exosomes to tumor masses can be achieved through either "passive" targeting, which relies on the inherent tropism of exosomes, or "active" targeting, which involves modifying the surface of exosomal membranes. Despite the numerous advantages of exosomes compared to synthetic nanoparticles, there are still obstacles to overcome to improve the efficiency of loading anti-cancer agents into exosomes. Additionally, there is a need to develop quantitative and qualitative analytical techniques for monitoring the delivery of exosomes and exosome-incorporated anticancer agents to the tumor parenchyma in vivo. [ABSTRACT FROM AUTHOR]

The main goal of modern pharmaceutical technology is to create new drug formulations that are safer and more effective. These formulations should allow targeted drug delivery, improved drug stability and bioavailability, fewer side effects, and reduced drug toxicity. One successful approach for achieving these objectives is using polymer microcarriers for drug delivery. They are effective for treating various diseases through different administration routes. When creating pharmaceutical systems, choosing the right drug carrier is crucial. Biomaterials have become increasingly popular over the past few decades due to their lack of toxicity, renewable sources, and affordability. Marine polysaccharides, in particular, have been widely used as substitutes for synthetic polymers in drug carrier applications. Their inherent properties, such as biodegradability and biocompatibility, make marine polysaccharide-based microcarriers a prospective platform for developing drug delivery systems. This review paper explores the principles of microparticle design using marine polysaccharides as drug carriers. By reviewing the current literature, the paper highlights the challenges of formulating polymer microparticles, and proposes various technological solutions. It also outlines future perspectives for developing marine polysaccharides as drug microcarriers. [ABSTRACT FROM AUTHOR]

Simple Summary: Silk fibroin (SF) from silkworms is exceptionally biocompatible and biodegradable. The nanoparticle delivery systems constructed with SF can improve drug delivery and enhance action efficiency. This review outlines the various nanoparticle delivery systems, focusing on the application and potential of eco-friendly SF as a delivery system in animal husbandry. The aim is to provide theoretical references for the further development and application of SF in animal husbandry. Silk fibroin (SF), a unique natural polymeric fibrous protein extracted from Bombyx mori cocoons, accounts for approximately 75% of the total mass of silk. It has great application prospects due to its outstanding biocompatibility, biodegradability, low immunogenicity, and mechanical stability. Additionally, it is non-toxic and environmentally friendly. Nanoparticle delivery systems constructed with SF can improve the bioavailability of the carriers, increase the loading rates, control the release behavior of the deliverables, and enhance their action efficiencies. Animal husbandry is an integral part of agriculture and plays a vital role in the development of the rural economy. However, the pillar industry experiences a lot of difficulties, like drug abuse while treating major animal diseases, and serious environmental pollution, restricting sustainable development. Interestingly, the limited use cases of silk fibroin nanoparticle (SF NP) delivery systems in animal husbandry, such as veterinary vaccines and feed additives, have shown great promise. This paper first reviews the SF NP delivery system with regard to its advantages, disadvantages, and applications. Moreover, we describe the application status and developmental prospects of SF NP delivery systems to provide theoretical references for further development in livestock production and promote the high-quality and healthy development of animal husbandry. [ABSTRACT FROM AUTHOR]

Optimising drug delivery to tumours remains an obstacle to effective cancer treatment. A prerequisite for successful chemotherapy is that the drugs reach all tumour cells. The vascular network of tumours, extravasation across the capillary wall and penetration throughout the extracellular matrix limit the delivery of drugs. Ultrasound combined with microbubbles has been shown to improve the therapeutic response in preclinical and clinical studies. Most studies apply microbubbles designed as ultrasound contrast agents. Acoustic Cluster Therapy (ACT®) is a novel approach based on ultrasound-activated microbubbles, which have a diameter 5–10 times larger than regular contrast agent microbubbles. An advantage of using such large microbubbles is that they are in contact with a larger part of the capillary wall, and the oscillating microbubbles exert more effective biomechanical effects on the vessel wall. In accordance with this, ACT® has shown promising therapeutic results in combination with various drugs and drug-loaded nanoparticles. Knowledge of the mechanism and behaviour of drugs and microbubbles is needed to optimise ACT®. Real-time intravital microscopy (IVM) is a useful tool for such studies. This paper presents the experimental setup design for visualising ACT® microbubbles within the vasculature of tumours implanted in dorsal window (DW) chambers. It presents ultrasound setups, the integration and alignment of the ultrasound field with the optical system in live animal experiments, and the methodologies for visualisation and analysing the recordings. Dextran was used as a fluorescent marker to visualise the blood vessels and to trace drug extravasation and penetration into the extracellular matrix. The results reveal that the experimental setup successfully recorded the kinetics of extravasation and penetration distances into the extracellular matrix, offering a deeper understanding of ACT's mechanisms and potential in localised drug delivery. [ABSTRACT FROM AUTHOR]

Metal sulfide nanoparticles are synthesized for their biomedical applications, including cancer drug targeting. This paper reports a novel nanocomposite made of praseodymium sulfide nanoparticles and poly-cyclodextrin. The praseodymium sulfide nanoparticles were synthesized hydrothermal, autoclaving the nitrate precursors at 150 °C for 18 hours. The material is characterized using XRD and shows an orthorhombic crystal system with high crystallinity. The size and morphology of the nanomaterial were optimized. The material shows a rod-shaped morphology, as seen in the TEM image, with 150 ± 3 nm length and 25 ± 5 nm width. Particle size analysis supports this size range. The colloidal particles were stable in the aqueous medium without precipitation at neutral pH. The elements in the material in the polymer-coated form and their electronic states are studied by X-ray photoelectron spectroscopy. Thermogravimetry confirms that the material contains about 18.5% of the weight of the polymer. The material has an observable magnetic property at room temperature due to the praseodymium element. The UV–vis–NIR absorption spectrum of the material shows a long absorption range that extends to 1200 nm. The drug 5-fluorouracil is encapsulated in the nanoparticles through host: guest association, and its release profile is analyzed. The release is modulated at a slightly acidic pH, indicating the pH-tunability. The nanoparticles and 5-fluorouracil were taken in the w/w ratio of 2:1 (2/1 mg in 1 mL of deionized water). Further, the in vitro anticancer activity of the drug-encapsulated material is screened on breast cancer and non-cancerous cell lines. The IC 50 values are reported, and the advantageous properties of the material as drug carriers are discussed. • Drug carrier nanorods are designed using praseodymium sulfide and poly-cyclodextrin. • The nanoparticles are weakly magnetic with low saturation. • It shows a long tail absorption band that extends up to the NIR-II wavelength range. • The encapsulated 5-fluorouracil is released continually for more than 10 days. • Drug-containing Pr2S3 nanoparticles are selectively active on MCF-7 cell lines. [ABSTRACT FROM AUTHOR]

A drug nanocrystal self-stabilized Pickering emulsion (DNSPE) is a novel Pickering emulsion with drug nanocrystals as the stabilizer. As a promising drug delivery system, DNSPEs have attracted increasing attention in recent years due to their high drug loading capacity and ability to reduce potential safety hazards posed by surfactants or specific solid particles. This paper comprehensively reviews the progress of research on DNSPEs, with an emphasis on the main factors influencing their construction, characteristics and measurement methods in vitro, and fate in vivo, and puts forward issues that need to be studied further. The review contributes to the advancement of DNSPE research and the promotion of their application in the field of drug delivery. [ABSTRACT FROM AUTHOR]

Effective drug delivery is essential for cancer treatment. Drug delivery systems, which can be tailored to targeted transport and integrated tumor therapy, are vital in improving the efficiency of cancer treatment. Peptides play a significant role in various biological and physiological functions and offer high design flexibility, excellent biocompatibility, adjustable morphology, and biodegradability, making them promising candidates for drug delivery. This paper reviews peptide-mediated drug delivery systems, focusing on self-assembled peptides and peptide–drug conjugates. It discusses the mechanisms and structural control of self-assembled peptides, the varieties and roles of peptide–drug conjugates, and strategies to augment peptide stability. The review concludes by addressing challenges and future directions. [ABSTRACT FROM AUTHOR]

Recently, neurological disorders have led to a growing global burden of fatalities and disabilities. The limited capacity for natural self‐regeneration poses a significant challenge in repairing nervous system injuries, which is closely related to the complex microenvironment and nonregenerative nature of neurons. Metal–organic frameworks (MOFs), with their distinctive structure and properties including high surface area, porosity, tunability, stimuli‐responsive behavior, biocompatibility, and biodegradability, stand as an auspicious platform for devising therapeutic strategies aiming at nerve regeneration and repair. By taking advantage of these characteristics, researchers have the opportunity to explore innovative methods including endogenous stimulation, magnetic response therapy, phototherapy, ultrasound therapy, and drug delivery systems for the treatment of neurological diseases. Moreover, MOFs‐based stem cell therapy also is developed to inhibit neuroinflammation and oxidative stress, promote axon growth, regulate stem cell differentiation, promote nerve regeneration, and finally restore the function of injured nerves. In this paper, the preparation strategy and biological characteristics of MOFs, highlighting their applications in repairing nerve injuries and treating neural stem cells is presented. Finally, an outlook on the future development and challenges in the field of neuroscience concerning MOFs is provided. [ABSTRACT FROM AUTHOR]

Noise‐induced hearing loss (NIHL) is a common outcome of excessive reactive oxygen species in the cochlea, and the targeted delivery of antioxidants to the inner ear is a potential therapeutic strategy. In this paper, a novel natural biomaterials‐derived multifunctional delivery system using silk fibroin‐polydopamine (PDA)‐composited inverse opal microcarriers (PDA@SFMCs) is presented for inner ear drug delivery and NIHL therapy. Due to their large specific surface area and interpenetrating nanochannels, PDA@SFMCs can rapidly load active biomolecules making them a convenient medium for the storage and delivery of such molecules. In addition, surface modification of PDA enables the microcarriers to remain in the round window niche, thus facilitating the precise local and directed delivery of loaded drugs. Based on these features, it is demonstrated here that n‐acetylcysteine‐loaded silk microcarriers have satisfactory antioxidant properties on cells and can successfully prevent NIHL in guinea pigs. These results indicate that the natural multifunctional silk microcarriers are promising agents for local inner ear drug delivery in the clinic. [ABSTRACT FROM AUTHOR]

The unique properties of ionic liquids (ILs), such as structural tunability, good solubility, chemical/thermal stability, favorable biocompatibility, and simplicity of preparation, have led to a wide range of applications in the pharmaceutical and biomedical fields. ILs can not only speed up the chemical reaction process, improve the yield, and reduce environmental pollution but also improve many problems in the field of medicine, such as the poor drug solubility, product crystal instability, poor biological activity, and low drug delivery efficiency. This paper presents a systematic and concise analysis of the recent advancements and further applications of ILs in the pharmaceutical field from the aspects of drug synthesis, drug analysis, drug solubilization, and drug crystal engineering. Additionally, it explores the biomedical field, covering aspects such as drug carriers, stabilization of proteins, antimicrobials, and bioactive ionic liquids. [ABSTRACT FROM AUTHOR]

Graphite carbon nitride (g-C3N 4) polymer with two-dimensional planar structure is a new star in nanodrug delivery systems in recent years because it shows characteristics of low cost, nontoxicity, biocompatibility and easy functionalization. However, conventional g-C3N4 shows bulk, macro size, small specific surface area and poor water solubility. To improve this, most works are always confined to physical ultrasound, oxidative peeling or template-strategy, which have the disadvantages of redundant steps, environment-unfriendliness and high cost. In this paper, a modified supramolecular self-assembled strategy was carried out to construct a novel graphitic carbon nitride nanoplatform (named by CA-MA X) using melamine and cyanuric as precursors. The chemical structure characterization, drug loading experiment and cell tests in vitro of the CA-MA X nanoplatform were carried out and discussed in detail. Results indicated that the obtained samples show enhanced specific surface area, more exposed groups and good biocompatibility. Compared to the traditional carbon nitride (named by MA-CN), the newly prepared CA-MA X carrier shows improved drug loading efficiency and good pH-responsive loading, as well as releasing. Cell uptake experiment demonstrates that CA-MA2-DOX can be swallowed by cancer cells and during treatment of the cancer cell process, the CA-MA2-DOX complex experiences phagocytizing by the cancer cell, controlled-release DOX and kills the cancer cell after DOX was passively diffused into the nucleus. CA-MA2-DOX exhibited significant in vitro antitumor activity. To our knowledge, this is the first time the supramolecular self-assembled method was used in carbon nitride nanocarrier construction for cancer treatment. g-C3N4 nano-platform was prepared via supramolecular self-assembly strategy, which is used as drug delivery for the first time to deliver small molecule drugs for cancer therapy. The obtained samples show higher specific surface area (78.9 m2/g), more exposed groups and good biocompatibility, making it more suitable to be used as drugs carrier. Compared to the traditional g-C3N4, it shows improved encapsulation efficiency, good pH response and a significant in vitro antitumor activity. [ABSTRACT FROM AUTHOR]

Vitamins are crucial for sustaining life because they play an essential role in numerous physiological processes. Vitamin deficiencies can lead to a wide range of severe health issues. In this context, there is a need to administer vitamin supplements through appropriate routes, such as the oral route, to ensure effective treatment. Therefore, understanding the pharmacokinetics of vitamins provides critical insights into absorption, distribution, and metabolism, all of which are essential for achieving the desired pharmacological response. In this review paper, we present information on vitamin deficiencies and emphasize the significance of understanding vitamin pharmacokinetics for improved clinical research. The pharmacokinetics of several vitamins face various challenges, and thus, this work briefly outlines the current issues and their potential solutions. We also discuss the feasibility of enhanced nanocarrier‐based pharmaceutical formulations for delivering vitamins. Recent studies have shown a preference for nanoformulations, which can address major limitations such as stability, solubility, absorption, and toxicity. Ultimately, the pharmacokinetics of pharmaceutical dosage forms containing vitamins can impede the treatment of diseases and disorders related to vitamin deficiency. [ABSTRACT FROM AUTHOR]

Hydrotropic solubilization is a technique that can be used to improve the solubility of drugs that are poorly soluble. This technique involves adding a large amount of a second solute, known as a hydrotrope, which increases the aqueous solubility of the poorly soluble drug. Hydrotropes such as sodium citrate, sodium benzoate, and urea have been shown to be effective in enhancing the solubility of poorly soluble drugs. This technique has several advantages over other solubility enhancement techniques, including its cost-effectiveness, eco-friendliness, and the fact that it does not require chemical modification of hydrophobic drugs or the use of organic solvents. Hydrotropic agents are now being used to develop various dosage forms, including solid dispersions, mouth-dissolving tablets, and injections, to improve poorly water-soluble drugs' therapeutic effectiveness and bioavailability. This review paper will provide an overview of hydrotropic solubilization techniques. [ABSTRACT FROM AUTHOR]

Several formulations have been developed in the current era using liposomes and niosomes as vesicular carriers, which have proven useful in oral drug delivery; nevertheless, their use is limited due to their gastrointestinal environment, including pH, enzymes, and bile salts. To overcome these difficulties, researchers are working on finding ways to improve the efficacy and stability of vesicles. Therefore bilosomes have been developed as promising vesicular carriers with the potential to deliver oral vaccines, parenteral and transdermal targeted drug delivery. In addition to incorporating hydrophilic as well as lipophilic drugs into vesicles, bilosomes are considered one of the most effective methods for enhancing bioavailability and efficacy. Bile acid-based bilosomes are rapidly growing in the current research areas and are expected to provide multiple applications in the pharmaceutical and biomedical fields that will occur in the future with bile salts. This paper briefly introduces the bilosomes of a new generation (structure), their mechanism of action, stability, physicochemical properties, and potential biomedical applications including in oral immunization. Furthermore, surface-engineered bilosomes are more effective than bare bilosomes in various animal models, but clinical trials are needed to assess their safety and efficacy. There is also a need for more research on scaling-up factors for commercializing bilosomal systems. [ABSTRACT FROM AUTHOR]

Additive manufacturing, widely known as 3D printing, has revolutionized the production of biomaterials. While conventional 3D-printed structures are perceived as static, 4D printing introduces the ability to fabricate materials capable of self-transforming their configuration or function over time in response to external stimuli such as temperature, light, or electric field. This transformative technology has garnered significant attention in the field of biomedical engineering due to its potential to address limitations associated with traditional therapies. Here, we delve into an in-depth review of 4D-printing systems, exploring their diverse biomedical applications and meticulously evaluating their advantages and disadvantages. We emphasize the novelty of this review paper by highlighting the latest advancements and emerging trends in 4D-printing technology, particularly in the context of biomedical applications. [ABSTRACT FROM AUTHOR]

In the therapy of placenta-originated diseases during pregnancy, the main challenges are fetal exposure to drugs, which can pass through the placenta and cause safety concerns for fetal development. The design of placenta-resident drug delivery system is an advantageous method to minimize fetal exposure as well as reduce adverse maternal off-target effects. By utilizing the placenta as a biological barrier, the placenta-resident nanodrugs could be trapped in the local placenta to concentrate on the treatment of this abnormal originated tissue. Therefore, the success of such systems largely depends on the placental retention capacity. This paper expounds on the transport mechanism of nanodrugs in the placenta, analyzes the factors that affect the placental retention of nanodrugs, and summarizes the advantages and concerns of current nanoplatforms in the treatment of placenta-originated diseases. In general, this review aims to provide a theoretical basis for the construction of placenta-resident drug delivery systems, which will potentially enable safe and efficient clinical treatment for placenta-originated diseases in the future. [ABSTRACT FROM AUTHOR]

Ongoing research is gradually broadening the idea of cancer treatment, with attention being focused on nanoparticles to improve the stability, therapeutic efficacy, targeting, and other important metrics of conventional drugs and traditional drug delivery methods. Studies have demonstrated that drug delivery carriers based on biomaterials (e.g., protein nanoparticles and lipids) and inorganic materials (e.g., metal nanoparticles) have potential anticancer effects. Among these carriers, self-assembled proteins and peptides, which are highly biocompatible and easy to standardize and produce, are strong candidates for the preparation of anticancer drugs. Breast cancer (BC) and cervical cancer (CC) are two of the most common and deadly cancers in women. These cancers not only threaten lives globally but also put a heavy burden on the healthcare system. Despite advances in medical care, the incidence of these two cancers, particularly CC, which is almost entirely preventable, continues to rise, and the mortality rate remains steady. Therefore, there is still a need for in-depth research on these two cancers to develop more targeted, efficacious, and safe therapies. This paper reviews the types of self-assembling proteins and peptides (e.g., ferritin, albumin, and virus-like particles) and natural products (e.g., soy and paclitaxel) commonly used in the treatment of BC and CC and describes the types of drugs that can be delivered using self-assembling proteins and peptides as carriers (e.g., siRNAs, DNA, plasmids, and mRNAs). The mechanisms (including self-assembly) by which the natural products act on CC and BC are discussed. The mechanism of action of natural products on CC and BC and the mechanism of action of self-assembled proteins and peptides have many similarities (e.g., NF-KB and Wnt). Thus, natural products using self-assembled proteins and peptides as carriers show potential for the treatment of BC and CC. [ABSTRACT FROM AUTHOR]

In recent years, polymeric materials have been used in a wide range of applications in a variety of fields. In particular, in the field of bioengineering, the use of natural biomaterials offers a possible new avenue for the development of products with better biocompatibility, biodegradability, and non-toxicity. This paper reviews the structural and physicochemical properties of alginate and hyaluronic acid, as well as the applications of the modified cross-linked derivatives in tissue engineering and drug delivery. This paper summarizes the application of alginate and hyaluronic acid in bone tissue engineering, wound dressings, and drug carriers. We provide some ideas on how to replace or combine alginate-based composites with hyaluronic-acid-based composites in tissue engineering and drug delivery to achieve better eco-economic value. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) could be produced by most cells and play an important role in disease development. As a subtype of EVs, exosomes exhibit suitable size, rich surface markers and diverse contents, making them more appealing as potential drug carriers. Compared with traditional synthetic nanoparticles, exosomes possess superior biocompatibility and much lower immunogenicity. This work reviewed the most up-to-date research progress of exosomes as carriers for nucleic acids, proteins and small molecule drugs for cancer and inflammation management. The drug loading strategies and potential cellular uptake behaviour of exosomes are highlighted, trying to provide reference for future exosome design and application. Exosomes are secreted by a variety of cells and play an important role in the process of inter-cell communication. This paper provides a comprehensive review focussing on the up-to-date applications of exosomes as carriers of nucleic acids, proteins and small molecule drugs for cancer and inflammation management. This paper briefly introduces the basic properties of exosomes, from definition, biogenesis to cellular uptake manners. Various strategies to enable exosomes to efficiently load cargoes are highlighted. Problems to be solved when using exosomes to deliver drugs are discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroblastoma is a rare type of cancer that usually affects children. The high-risk patients' expected survival rate is less than 50%. One reason is the lack of precision in the standard treatment protocol: a one-size-fits-all multi-modal therapy. The study presented in this paper was designed to address this deficit by optimising the use of two chemotherapeutic agents—vincristine and cyclophosphamide—during induction chemotherapy—the part of the protocol that shrinks the primary tumour before surgical removal. We combined a mathematical model and an optimisation algorithm to identify the best chemotherapy schedules for a cohort of virtual patients with different initial tumour compositions. Our results reveal novel strategies to exploit a pair of drugs with different levels of efficacy, provide a platform on which to individualise induction chemotherapy, and lay the foundation for a personalised therapy that leverages targeted therapies, multi-region sequencing, liquid biopsies, and modern computational methods to improve today's multi-modal therapy. Neuroblastoma is the most common extra-cranial solid tumour in children. Despite multi-modal therapy, over half of the high-risk patients will succumb. One contributing factor is the one-size-fits-all nature of multi-modal therapy. For example, during the first step (induction chemotherapy), the standard regimen (rapid COJEC) administers fixed doses of chemotherapeutic agents in eight two-week cycles. Perhaps because of differences in resistance, this standard regimen results in highly heterogeneous outcomes in different tumours. In this study, we formulated a mathematical model comprising ordinary differential equations. The equations describe the clonal evolution within a neuroblastoma tumour being treated with vincristine and cyclophosphamide, which are used in the rapid COJEC regimen, including genetically conferred and phenotypic drug resistance. The equations also describe the agents' pharmacokinetics. We devised an optimisation algorithm to find the best chemotherapy schedules for tumours with different pre-treatment clonal compositions. The optimised chemotherapy schedules exploit the cytotoxic difference between the two drugs and intra-tumoural clonal competition to shrink the tumours as much as possible during induction chemotherapy and before surgical removal. They indicate that induction chemotherapy can be improved by finding and using personalised schedules. More broadly, we propose that the overall multi-modal therapy can be enhanced by employing targeted therapies against the mutations and oncogenic pathways enriched and activated by the chemotherapeutic agents. To translate the proposed personalised multi-modal therapy into clinical use, patient-specific model calibration and treatment optimisation are necessary. This entails a decision support system informed by emerging medical technologies such as multi-region sequencing and liquid biopsies. The results and tools presented in this paper could be the foundation of this decision support system. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic tumours present significant treatment challenges due to their resistance to chemotherapy and complex tumour microenvironment. Choosing the appropriate preclinical models and understanding how their characteristics affect drug delivery to the tumours is essential for designing clinically relevant experiments. This study investigates pancreatic tumours growing orthotopically or subcutaneously and presents the properties of their tumour microenvironments and their impacts on drug delivery. Pancreatic ductal adenocarcinoma (PDAC) remains a challenging malignancy, mainly due to its resistance to chemotherapy and its complex tumour microenvironment characterised by stromal desmoplasia. There is a need for new strategies to improve the delivery of drugs and therapeutic response. Relevant preclinical tumour models are needed to test potential treatments. This paper compared orthotopic and subcutaneous PDAC tumour models and their suitability for drug delivery studies. A novel aspect was the broad range of tumour properties that were studied, including tumour growth, histopathology, functional vasculature, perfusion, immune cell infiltration, biomechanical characteristics, and especially the extensive analysis of the structure and the orientation of the collagen fibres in the two tumour models. The study unveiled new insights into how these factors impact the uptake of a fluorescent model drug, the macromolecule called 800CW. While the orthotopic model offered a more clinically relevant microenvironment, the subcutaneous model offered advantages for drug delivery studies, primarily due to its reproducibility, and it was characterised by a more efficient drug uptake facilitated by its collagen organisation and well-perfused vasculature. The tumour uptake seemed to be influenced mainly by the structural organisation and the alignment of the collagen fibres and perfusion. Recognising the diverse characteristics of these models and their multifaceted impacts on drug delivery is crucial for designing clinically relevant experiments and improving our understanding of pancreatic cancer biology. [ABSTRACT FROM AUTHOR]

Simple Summary: The investigation of chemotherapy combined with anti-angiogenesis has garnered significant attention from researchers. The aim of this study is to provide a numerical model, the first of its kind, considering more realistic phenomena in simulating drug delivery into a solid tumor with a remodeled dynamic microvascular network affected by the anti-angiogenic agent, angiostatin. This research aims to open a new horizon in understanding the efficiency of combination therapy involving anti-angiogenesis and chemotherapy. Results show that, for improving drug delivery with the aid of anti-angiogenesis, the uniformity of micro-vessel distribution, accompanied by the modification in drug exposure schedule caused by the alterations in transport properties induced by vascular normalization, is more effective than the suppression of the microvasculature. Therefore, it can be concluded that the 39% enhancement in uniformity of drug delivery in R = 0.2 cm is a result of the well-proportioned distribution of the capillary network in the second approach of anti-angiogenic therapy. The present study develops a numerical model, which is the most complex one, in comparison to previous research to investigate drug delivery accompanied by the anti-angiogenesis effect. This paper simulates intravascular blood flow and interstitial fluid flow using a dynamic model. The model accounts for the non-Newtonian behavior of blood and incorporates the adaptation of the diameter of a heterogeneous microvascular network derived from modeling the evolution of endothelial cells toward a circular tumor sprouting from two-parent vessels, with and without imposing the inhibitory effect of angiostatin on a modified discrete angiogenesis model. The average solute exposure and its uniformity in solid tumors of different sizes are studied by numerically solving the convection-diffusion equation. Three different methodologies are considered for simulating anti-angiogenesis: modifying the capillary network, updating the transport properties, and considering both microvasculature and transport properties modifications. It is shown that anti-angiogenic therapy decreases drug wash-out in the periphery of the tumor. Results show the decisive role of microvascular structure, particularly its distribution, and interstitial transport properties modifications induced via vascular normalization on the quality of drug delivery, such that it is improved by 39% in uniformity by the second approach in R = 0.2 cm. [ABSTRACT FROM AUTHOR]

Metal nanoparticles having magnetic properties are exciting for application in the directed transport of anticancer drugs encapsulated in them. To ensure drug‐loading capacity and controlled release, surface modification with host molecules is a fascinating choice. In this paper, we report the synthesis and surface modification of magnetic cobalt metal nanoparticles with oligosaccharide host molecules (β‐cyclodextrin) tethered on the surface. A β‐cyclodextrin‐folate derivative is synthesized and characterized using Infrared‐, Nuclear Magnetic Resonance‐, and Matrix‐Assisted Laser Deposition Ionization‐Time of Flight mass spectrometry. The size of the cobalt nanoparticles carrying the host molecule on the surface is ~10 nm. The nanoparticles are characterized using X‐Ray Diffraction, Transmission Electron Microscopy, particle size analyzer, Energy‐Dispersive X‐ray, and X‐ray Photoelectron Spectroscopy. The bare magnetic nanoparticles also show a strong saturation magnetization of 142.21 emu g−1. The chemotherapeutic drug 5‐fluorouracil is loaded on the surface‐modified cobalt nanoparticles through host: guest complexation mode and its controlled release is measured in‐vitro. The slow release is spread over more than 14 days, and a complete release of the loaded therapeutic cargo is not reached. The release is pH‐dependent and changes with acidic levels of the medium. The anticancer activity of the drug‐loaded nanocarrier on MDA‐MB‐231 (breast cancer) cells is investigated. The mechanism of cell death is studied, and the cells are found inhibited in the synthesis phase. Flow cytometric analysis shows that 79.70 % of the empty nanocarrier‐treated and 74.86 % 5‐fluorouracil‐loaded nanocarrier‐treated MDA‐MB‐231 cells were in the early apoptosis phase. This new combination nanocarrier is intriguing owing to its structural and magnetic properties, and the action on cell lines. [ABSTRACT FROM AUTHOR]

[Display omitted] Targeted delivery along with controlled drug release is considered crucial in development of a drug delivery system (DDS) for efficient cancer treatment. In this paper, we present a strategy to obtain such a DDS by utilizing disulfide-incorporated mesoporous organosilica nanoparticles (MONs), which were engineered to minimize the surface interactions with proteins for better targeting and therapeutic performance. That is, after MONs were loaded with a chemodrug doxorubicin (DOX) through the inner pores, their outer surface was treated for conjugation to the glutathione-S-transferase (GST)-fused cell-specific affibody (Afb) (GST-Afb). These particles exhibited prompt responsivity to the SS bond-dissociating glutathione (GSH), which resulted in considerable degradation of the initial particle morphology and DOX release. As the protein adsorption to the MON surface appeared largely reduced, their targeting ability with GSH-stimulated therapeutic activities was demonstrated in vitro by employing two kinds of the GST-Afb protein, which target human cancer cells with the surface membrane receptor, HER2 or EGFR. Compared with unmodified control particles, the presented results show that our system can significantly enhance cancer-therapeutic outcomes of the loaded drug, offering a promising way of designing a more efficacious DDS. [ABSTRACT FROM AUTHOR]

Commonly, it is accepted that oncology treatment would yield outcomes with a certain determinism without any quantitative support or mathematical model that establishes such determinations. Nowadays, with the advent of nanomedicine, the targeting drug delivery scheme has emerged, whose central objective is the uptake of nanoparticles by tumors. Once they are injected into the bloodstream, it is unclear as to which process governs the directing of nanoparticles towards the desired target, deterministic or stochastic. In any scenario, an optimal outcome, small toxicity and minimal dispersion of drugs is expected. Commonly, it is expected that an important fraction of them can be internalized into tumor. In this manner, due to the fraction of nanoparticles that have failed to uptake, the success of the drug delivery scheme might be at risk. In this paper, a theory based on the sequence electrodynamics–diffusion–Bayes theorem is presented. The Bayesian probability that emerges at the end of the sequence might be telling us that dynamical processes based on the injection of electrically charged nanoparticles might be dictated by stochastic formalism. Thus, rather than expecting a deterministic process, the chain of events would convert the drug delivery scheme to be dependent on a sequence of conditional probabilities. [ABSTRACT FROM AUTHOR]