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Pancreatic cancer (PC) remains the predominant type of upper gastrointestinal tract cancer, associated with heightened morbidity and a survival rate below 12%. While immunotherapy has brought about transformative changes in the standards of care for most solid tumors, its application in PC is hindered by the ''cold tumor'' microenvironment, marked by the presence of immunosuppressive cells. Modest response rates in PC are attributed, in part to, the fibrotic stroma that obstructs the delivery of systemic immunotherapy. Furthermore, the occurrence of immune-related adverse events (iRAEs) often necessitates the use of sub-therapeutic doses or treatment discontinuation. In the pursuit of innovative approaches to enhance the effectiveness of immunotherapy for PC, implantable drug delivery devices and scaffolds emerge as promising strategies. These technologies offer the potential for sustained drug delivery directly to the tumor site, overcoming stromal barriers, immunosuppression, T cell exclusion, immunotherapy resistance, optimizing drug dosage, and mitigating systemic toxicity. This review offers a comprehensive exploration of pancreatic ductal adenocarcinoma (PDAC), the most common and aggressive form of PC, accompanied by a critical analysis of the challenges the microenvironment presents to the development of successful combinational immunotherapy approaches. Despite efforts, these approaches have thus far fallen short in enhancing treatment outcomes for PDAC. The review will subsequently delve into the imperative need for refining delivery strategies, providing an examination of past and ongoing studies in the field of localized immunotherapy for PDAC. Addressing these issues will lay the groundwork for the development of effective new therapies, thereby enhancing treatment response, patient survival, and overall quality of life for individuals diagnosed with PDAC. [Display omitted] [ABSTRACT FROM AUTHOR]

At the early stages of drug development, the amount of drug materials is rather limited. In this case, viscosity measurement is often postponed to the later stages, where grams of proteins can be produced. Therefore, it is necessary to develop a viscometer capable of measuring the viscosity with high accuracy while requiring low sample volume. This study presents a novel viscosity measurement technique based on measuring the resonance frequency and motional resistance of a micropillar-enhanced acoustic wave (μPAW) device. The μPAW was developed by fabricating micropillars on the quartz crystal microbalance substrate in order to achieve ultra-high sensitivity, thanks to a unique coupling between the micropillar and the resonator. The experimental measurements demonstrated a nonlinear relationship between the density and viscosity of the fluid and the response of μPAW. A calibration correlation was developed using the response of μPAW in aqueous glycerol and sucrose solutions. The measurements were then extended using high-concentration BSA solutions as the model of protein solution. The main advantage of the μPAW device in this work over other viscometers is the ability to simultaneously measure solution viscosity and protein adsorption on the surface. This is a huge step forward in the development of sensing systems for the pharmaceutical industry, where real-time sensing of target biological proteins and measuring the viscosity of a solution is required. [ABSTRACT FROM AUTHOR]

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This article explores the significance of precision dosing in medicine and the factors that contribute to achieving accurate dosages. It emphasizes the integration of data, digital health, and advanced technologies to achieve precision dosage. The article discusses the implications of incorrect dosing, such as adverse reactions and failed clinical trials. It also examines the evolution of dose selection methods and the complexities involved in determining the right dose for different therapeutic approaches. The article highlights the shift towards precision medicine and the importance of personalized dosing that considers individual patient characteristics. It explores the use of advanced quantitative methodologies, real-world data, digital health technologies, and artificial intelligence in optimizing dosing regimens. The article addresses the challenges and ethical considerations associated with these innovations and emphasizes the need for collaboration among stakeholders to drive advancements in precision dosing. [Extracted from the article]

Background: Although a variety of drug delivery devices have been launched in recent years, few studies have comprehensively investigated the market trends of combination drugs and medical devices approved or certified in Japan and the regulatory challenges related to their approval. Among the drug delivery devices, autoinjectors are more convenient than traditional prefilled syringes and are designed with safety features to prevent needlestick accidents, allowing self-injection by patients. Therefore, autoinjectors have been incorporated into the treatment of various diseases and have shown significant growth among drug delivery devices. Aim: This study aimed to investigate the market trends of combination drugs approved in Japan, especially those with autoinjector formulations, and to explore the challenges in the regulatory aspects of combination drugs. Methods: Information on the number of marketed drugs and medical devices was obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) database using specific definitions. We looked at the annual changes in the number of drug delivery devices approved and certified as combination drugs or medical devices and the number of canceled certifications. We also examined the classification and main certification criteria for Japanese medical device nomenclature. Results: The study suggested that the number of combination drugs with autoinjector formulations is increasing, replacing previously approved or certified pen-type medication injectors. Moreover, 53% of all drug products were approved for autoinjector formulations after the initial authorization approval in Japan, and more than half of them obtained approval for additional formulations for autoinjectors within five years of the initial authorization approval, with the largest number of cases obtaining approval for additional formulations two years later. Conclusion: The lack of clear regulatory requirements for autoinjectors may lead to confusion among applicants. Furthermore, there are challenges in filing regulatory applications, thus hindering the rapid launch of combination drugutilizing devices with superior usability. [ABSTRACT FROM AUTHOR]

Medication adherence is an essential aspect of healthcare for patients and is important for achieving medical objectives. However, the lack of standard techniques for measuring adherence is a global concern, making it challenging to accurately monitor and measure patient medication regimens. The use of sensor technology for medication adherence monitoring has received much attention lately since it makes it possible to continuously observe patients' medication adherence behavior. Sensor devices or smart wearables utilize state-of-the-art machine learning (ML) methods to analyze intricate data patterns and provide predictions accurately. The key aim of this work is to develop a sensor-based hand gesture recognition model to predict medication activities. In this research, a smart sensor device-based hand gesture prediction model is developed to recognize medication intake activities. The device includes a tri-axial gyroscope, geometric, and accelerometer sensors to sense and gather data from hand gestures. A smartphone application gathers hand gesture data from the sensor device, which is then stored in the cloud database in a.csv format. These data are collected, processed, and classified to recognize the medication intake activity using the proposed novel neural network model called Sea Horse Optimization–Deep Neural Network (SHO-DNN). The SHO technique is implemented to update the biases and weights and the number of hidden layers in the DNN model. By updating these parameters, the DNN model is improved in classifying the samples of hand gestures to identify the medication activities. The research model demonstrates impressive performance, with an accuracy of 98.59%, sensitivity of 97.82%, precision of 98.69%, and an F1 score of 98.48%. Hence, the proposed model outperformed the most available models in all the aforementioned aspects. The results indicate that this model is a promising approach for medication adherence monitoring in healthcare applications, instilling confidence in its effectiveness. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related mortality worldwide, largely due to the limited efficacy of anticancer drugs, which is primarily attributed to insufficient doses reaching the lungs. Additionally, patients undergoing treatment experience severe systemic adverse effects due to the distribution of anticancer drugs to non-targeted sites. In light of these challenges, there has been a growing interest in pulmonary administration of drugs for the treatment of lung cancer. This route allows drugs to be delivered directly to the lungs, resulting in high local concentrations that can enhance antitumor efficacy while mitigating systemic toxic effects. However, pulmonary administration poses the challenge of overcoming the mechanical, chemical, and immunological defenses of the respiratory tract that prevent the inhaled drug from properly penetrating the lungs. To overcome these drawbacks, the use of nanoparticles in inhaler formulations may be a promising strategy. Nanoparticles can assist in minimizing drug clearance, increasing penetration into the lung epithelium, and enhancing cellular uptake. They can also facilitate increased drug stability, promote controlled drug release, and delivery to target sites, such as the tumor environment. Among them, chitosan-based nanoparticles demonstrate advantages over other polymeric nanocarriers due to their unique biological properties, including antitumor activity and mucoadhesive capacity. These properties have the potential to enhance the efficacy of the drug when administered via the pulmonary route. In view of the above, this paper provides an overview of the research conducted on the delivery of anticancer drug-loaded chitosan-based nanoparticles incorporated into inhaled drug delivery devices for the treatment of lung cancer. Furthermore, the article addresses the use of emerging technologies, such as siRNA (small interfering RNA), in the context of lung cancer therapy. Particularly, recent studies employing chitosan-based nanoparticles for siRNA delivery via the pulmonary route are described. [ABSTRACT FROM AUTHOR]

The fundamental problem in electronic cooling systems is the implementation of a cavity such that it can be used to provide localized cooling to specific components, such as CPUs or GPUs, enhancing their performance and longevity. It can also be used in microfluidic devices for controlled drug delivery, where precise control of fluid flow is crucial. The present article numerically explores the free convection non-Newtonian Casson hybrid nanofluid phenomena that occur within an H-shaped cavity while heated from the middle. The heating efficiency and heat flow in a cavity are influenced by perpendicular hot walls that connect two vertical closed channels. A numerical solution is obtained by implementing the Galerkin finite element method to solve the partial differential equation. The numerical outcomes are depicted on the contour of streamlines and isotherms for different parameters in the following ranges: 0.1 ≤ η ≤ 0.4, 0.005 ≤ ϕ h p ≤ 0.020 , 0.1 ≤ γ ≤ 2, and 103 ≤ Ra ≤ 106 at fixed Pr = 6.2. In addition, line graphs show rate of heat transfer within the enclosure using the average Nusselt number for these parameters. Increased aspect ratios (η = 0.4) result in a minimal rate of heat transfer enhancement, whereas decreasing η leads to a significantly higher average Nusselt number and maximum heat transfer within the cavity. The convective rate of heat transfer increases with the presence of hybrid nanoparticles inside an H-shaped cavity for all Rayleigh numbers. The rotation of the Casson hybrid nanofluid also rises as the volume ratio of nanoparticles increases. For a fixed aspect ratio (A.R) of 0.1, the heat dissipation is 6.91% at a lower ϕhp value of 0.005 at a fixed Ra value of 105. However, it increases to 7.072% for a higher ϕhp value of 0.02 at Ra = 105. With increasing Ra number, ϕhp, and γ, the number NuAve increases. [ABSTRACT FROM AUTHOR]

Bone defect is one of the urgent problems to be solved in clinics, and it is very important to construct efficient scaffold materials to facilitate bone tissue regeneration. Hydrogels, characterized by their unique three-dimensional network structure, serve as excellent biological scaffold materials. Their internal pores are capable of loading osteogenic drugs to expedite bone formation. The rate and quality of new bone formation are intimately linked with immune regulation and vascular remodeling. The strategic sequential release of drugs to balance inflammation and regulate vascular remodeling is crucial for initiating the osteogenic process. Through the design of hydrogel microstructures, it is possible to achieve sequential drug release and the drug action time can be prolonged, thereby catering to the multi-systemic collaborative regulation needs of osteosynthesis. The drug release rate within the hydrogel is governed by swelling control systems, physical control systems, chemical control systems, and environmental control systems. Utilizing these control systems to design hydrogel materials capable of multi-drug delivery optimizes the construction of the bone microenvironment. Consequently, this facilitates the spatiotemporal controlled released of drugs, promoting bone tissue regeneration. This paper reviews the principles of the controlled release system of various sustained-release hydrogels and the advancements in research on hydrogel multi-drug delivery systems for bone tissue regeneration. [Display omitted] • This paper explores a critical issue in the field of bone tissue regeneration, providing new insights and solutions. • This paper outlines the latest developments in hydrogel materials featuring multi-drug delivery capabilities. • This paper concludes the spatiotemporal controlled released hydrogels through analysis of bone regeneration procedures. [ABSTRACT FROM AUTHOR]

Objective: To review the existing literature on the application of computational fluid dynamics methods to study nasal particle deposition and to summarize and analyze the factors affecting nasal particle deposition in order to provide theoretical references for the development of future transnasal drug delivery devices and the prevention of respiratory‐related diseases. Data Source: PubMed and CNKI databases. Methods: A search of all current literature (up to and including February 2023) was conducted. Search terms related to the topic of factors influencing nasal particle deposition were identified, and queries were conducted to identify relevant articles. Results: Both the properties of the particles themselves and the environmental conditions external to the particles can affect particle deposition in the nasal cavity, with particle deposition showing a positive correlation with particle size, particle density, and airflow velocity, with increasing subject age leading to a decrease in deposition, and with the relationship between airflow temperature and humidity still requiring more research to further explore. Conclusions: With the popularity of computational fluid dynamics, more and more scholars have applied computational fluid dynamics technology to explore the influence of different parameters on particle deposition. By summarizing and analyzing the influence law of various factors on deposition, it can provide a theoretical basis for the future development and application of transnasal drug delivery devices and the prevention of respiratory‐related diseases, which makes a significant contribution to the optimization of clinical disease prevention and treatment. Level of Evidence: NA. [ABSTRACT FROM AUTHOR]

The importance of biomaterials lies in their fundamental roles in medical applications such as tissue engineering, drug delivery, implantable devices, and radiological phantoms, with their interactions with biological systems being critically important. In recent years, advancements in deep learning (DL), artificial intelligence (AI), machine learning (ML), supervised learning (SL), unsupervised learning (UL), and reinforcement learning (RL) have significantly transformed the field of biomaterials. These technologies have introduced new possibilities for the design, optimization, and predictive modeling of biomaterials. This review explores the applications of DL and AI in biomaterial development, emphasizing their roles in optimizing material properties, advancing innovative design processes, and accurately predicting material behaviors. We examine the integration of DL in enhancing the performance and functional attributes of biomaterials, explore AI-driven methodologies for the creation of novel biomaterials, and assess the capabilities of ML in predicting biomaterial responses to various environmental stimuli. Our aim is to elucidate the pivotal contributions of DL, AI, and ML to biomaterials science and their potential to drive the innovation and development of superior biomaterials. It is suggested that future research should further deepen these technologies' contributions to biomaterials science and explore new application areas. [ABSTRACT FROM AUTHOR]

Simple Summary: Three-dimensional printing technology is a method of creating a three-dimensional object layer by layer using a computer-generated design. This method has enabled the production of custom models of organs or organ parts, leading to the emergence of "personalized medicine". The materials used in 3D printing include plastic, metal, and polymers. This review discusses the current state and future prospects of six biomaterials used in veterinary medicine and ophthalmology. Polycaprolactone is suitable for replacing hard tissue defects and is well tolerated in the eye, making it useful for ocular drug delivery devices. Pluronic is used for bone tissue engineering applications and could also be employed for drug delivery in ophthalmology. Silk is used for composite osteogenic scaffolds and vascular grafts, and it may be tested for creating protective lenses for the eye. Collagen is used to produce bioengineered corneas to improve the treatment of corneal ulcers. Alginate is used in cardiac and orthopedic procedures and is also employed in various ocular delivery systems for corneal repair. Hyaluronic acid is commonly used as a lubricant and can serve as a regenerative scaffold during the corneal healing process. In recent years, there has been a growing interest in 3D printing technology within the field of bioengineering. This technology offers the ability to create devices with intricate macro- and micro-geometries, as well as specific models. It has particularly gained attention for its potential in personalized medicine, allowing for the production of organ or tissue models tailored to individual patient needs. Further, 3D printing has opened up possibilities to manufacture structures that can substitute, complement, or enhance damaged or dysfunctional organic parts. To apply 3D printing in the medical field, researchers have studied various materials known as biomaterials, each with distinct chemical and physical characteristics. These materials fall into two main categories: hard and soft materials. Each biomaterial needs to possess specific characteristics that are compatible with biological systems, ensuring long-term stability and biocompatibility. In this paper, we aim to review some of the materials used in the biomedical field, with a particular focus on those utilized in veterinary medicine and ophthalmology. We will discuss the significant findings from recent scientific research, focusing on the biocompatibility, structure, applicability, and in vitro and in vivo biological characteristics of two hard and four soft materials. Additionally, we will present the current state and prospects of veterinary ophthalmology. [ABSTRACT FROM AUTHOR]

Biodegradable polymers such as polylactic‐co‐glycolic acids (PLGA) are used for various implantable devices such as tissue scaffolds, drug delivery devices, and biosensors in different forms. However, high‐resolution patterning of biodegradable polymers on implantable devices has not been explored much yet. While electrohydrodynamic printing (EHD) can achieve high‐resolution printing compared to other printing methods, EHD printing of PLGA solutions is rarely attempted due to unstable printing. Such printing instability originates from the volatile nature of PLGA inks, and it causes nozzle clogging or change of ink conditions during printing. Here, PLGA ink formulation and a voltage input profile are studied for stable and high‐resolution EHD printing. Addition of glycerol at an optimal ratio as well as the control of voltage pulse shape strongly influenced both the stability and resolution of EHD printing of PLGA patterns. With the optimized inks and voltage inputs, stable printing of PLGA micropatterns down to 5 µm is achieved on both conductive and insulating surfaces for controlled drug release. Furthermore, use of a ring type electrode allows for EHD printing of PLGA micropatterns on 3D surfaces of PLLA tubes and stent struts. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease with multifactorial etiology and intricate pathogenesis. In RA, repeated monotherapy is frequently associated with inadequate efficacy, drug resistance, and severe side effects. Therefore, a shift has occurred in clinical practice toward combination therapy. However, conventional combination therapy encounters several hindrances, including low selectivity to arthritic joints, short half-lives, and varying pharmacokinetics among coupled drugs. Emerging nanotechnology offers an incomparable opportunity for developing advanced combination therapy against RA. First, it allows for co-delivering multiple drugs with augmented physicochemical properties, targeted delivery capabilities, and controlled release profiles. Second, it enables therapeutic nanomaterials development, thereby expanding combination regimens to include multifunctional nanomedicines. Lastly, it facilitates the construction of all-in-one nanoplatforms assembled with multiple modalities, such as phototherapy, sonodynamic therapy, and imaging. Thus, nanotechnology offers a promising solution to the current bottleneck in both RA treatment and diagnosis. This review summarizes the rationale, advantages, and recent advances in nano-empowered combination therapy for RA. It also discusses safety considerations, drug–drug interactions, and the potential for clinical translation. Additionally, it provides design tips and an outlook on future developments in nano-empowered combination therapy. The objective of this review is to achieve a comprehensive understanding of the mechanisms underlying combination therapy for RA and unlock the maximum potential of nanotechnology, thereby facilitating the smooth transition of research findings from the laboratory to clinical practice. [ABSTRACT FROM AUTHOR]

Controlling microrobot locomotion in vessels and capillaries is crucial for precise drug delivery and minimally invasive surgeries. However, this is challenging due to the complex interactions with red blood cells (RBCs) and the difficulty navigating within the dense environment. Here, we construct a numerical framework to evaluate the relative resistance coefficient ( C r * ) of a microrobot propelled through RBC suspensions. Our experiments validate the numerical results. We find that C r * increases for smaller microrobots and higher hematocrit levels, while magnetic force strength weakly impacts C r * . C r * is smaller than the resistance coefficient of a macroscale robot estimated from the apparent viscosity of the RBC suspension. The aspect ratio of a prolate ellipsoidal microrobot influences C r * along its long-axis direction. Additionally, machine learning accurately predicts C r * . These insights could enhance the design and control of microrobots for medical applications. Controlling microrobot movement in blood vessels is vital for medical treatments but is challenging due to red blood cells. This study combines simulations, experiments, and machine learning to demonstrate how hematocrit levels and robot geometry affect its locomotion characteristics in blood [ABSTRACT FROM AUTHOR]

Lung cancer remains as the leading cause of cancer-related fatalities globally, posing significant challenges to conventional treatment methods, particularly in advanced stages where limitations and adverse effects are prevalent. Nanotechnology offers promising solutions to enhance lung cancer therapy. Inorganic nanomaterials, such as metal nanoparticles, rare earth elements, and carbonaceous materials, exhibit unique properties that can address these challenges. Metal nanoparticles facilitate targeted drug delivery, biosensing, and imaging, while rare earth elements demonstrate selective cytotoxic effects and imaging capabilities. Carbonaceous materials find applications in biosensing and drug delivery, including carbon ion radiotherapy. These advancements in inorganic nanomaterials present an opportunity to revolutionize lung cancer treatment, potentially leading to improved outcomes and better patient well-being. This paper focuses on recent progress in utilizing inorganic nanomaterials for treating lung cancer, aiming to provide a clearer understanding of their benefits compared to conventional treatments, along with an in-depth examination of their associated limitations and adverse effects. [Display omitted] [ABSTRACT FROM AUTHOR]

Heart-on-a-chip (HoC) has emerged as a highly efficient, cost-effective device for the development of engineered cardiac tissue, facilitating high-throughput testing in drug development and clinical treatment. HoC is primarily used to create a biomimetic microphysiological environment conducive to fostering the maturation of cardiac tissue and to gather information regarding the real-time condition of cardiac tissue. The development of architectural design and advanced manufacturing for these "3S" components, scaffolds, stimulation, and sensors is essential for improving the maturity of cardiac tissue cultivated on-chip, as well as the precision and accuracy of tissue states. In this review, the typical structures and manufacturing technologies of the "3S" components are summarized. The design and manufacturing suggestions for each component are proposed. Furthermore, key challenges and future perspectives of HoC platforms with integrated "3S" components are discussed. [ABSTRACT FROM AUTHOR]

Poly(lactic acid) (PLA) is widely used in the field of medicine due to its biocompatibility, versatility, and cost-effectiveness. Three-dimensional (3D) printing or the systematic deposition of PLA in layers has enabled the fabrication of customized scaffolds for various biomedical and clinical applications. In tissue engineering and regenerative medicine, 3D-printed PLA has been mostly used to generate bone tissue scaffolds, typically in combination with different polymers and ceramics. PLA's versatility has also allowed the development of drug-eluting constructs for the controlled release of various agents, such as antibiotics, antivirals, anti-hypertensives, chemotherapeutics, hormones, and vitamins. Additionally, 3D-printed PLA has recently been used to develop diagnostic electrodes, prostheses, orthoses, surgical instruments, and radiotherapy devices. PLA has provided a cost-effective, accessible, and safer means of improving patient care through surgical and dosimetry guides, as well as enhancing medical education through training models and simulators. Overall, the widespread use of 3D-printed PLA in biomedical and clinical settings is expected to persistently stimulate biomedical innovation and revolutionize patient care and healthcare delivery. [ABSTRACT FROM AUTHOR]

Neurodegenerative disorders cause most physical and mental disabilities, and therefore require effective treatment. The blood–brain barrier (BBB) prevents drug molecules from crossing from the blood to the brain, making brain drug delivery difficult. Implantable devices could provide sustained and regulated medication to solve this problem. Two electrolytes (0.3 M oxalic acid and 0.3 M sulphuric acid) were used to anodise Al2O3 nanoporous membranes, followed by a third anodisation in concentrated H2SO4 to separate the through-hole membranes from the aluminium substrate. FTIR, AFM, and SEM/EDX were used to characterise the membranes' structure and morphology. The effects of the anodisation time and electrolyte type on the AAO layer pore density, diameter, interpore distance, and thickness were examined. As a model drug for neurodegenerative disorders, donepezil hydrochloride (DHC) was loaded onto thin alumina nanoporous membranes. The DHC release profiles were characterised at two concentrations using a UV–Vis spectrophotometer. Oxalic acid membranes demonstrated an average pore diameter of 39.6–32.5 nm, which was two times larger than sulphuric acid membranes (22.6–19.7 nm). After increasing the anodisation time from 3 to 5 h, all of the membranes showed a reduction in pore diameter that was stable regardless of the electrolyte type or period. Drug release from oxalic acid-fabricated membranes was controlled and sustained for over 2 weeks. Thus, nanoporous membranes as implantable drug delivery systems could improve neurodegenerative disease treatment. [ABSTRACT FROM AUTHOR]

This study investigates recent advancements in drug delivery systems (DDS) for tissue engineering, emphasizing their role in the targeted and sustained release of therapeutic agents to promote tissue regeneration. It explores innovative approaches, including nanotechnology, 3D printing, and immunomodulation, which enhance the effectiveness of tissue engineering therapies. This review provides a brief overview of the fundamentals of controlled drug delivery, comparing controlled release and slow release. It also introduces drug delivery vehicles, drug release mechanisms, release kinetics, and recent applications in the field of regenerative medicine. It highlights the benefits of nanotechnology, such as increased drug loading capacity and stability, and identifies 3D-printed scaffolds as a promising method for sustained drug release. Additionally, the growing interest in using DDS for immunomodulation to improve tissue regeneration is discussed. The rapidly evolving field of DDS in tissue engineering presents new opportunities for developing more effective therapeutic strategies. This study contributes to the understanding of these innovations and their potential applications. [ABSTRACT FROM AUTHOR]

Hydrogels with particulates, including proteins, drugs, nanoparticles, and cells, enable the development of new and innovative biomaterials. Precise control of the spatial distribution of these particulates is crucial to produce advanced biomaterials. Thus, there is a high demand for manufacturing methods for particle-laden hydrogels. In this context, 3D printing of hydrogels is emerging as a promising method to create numerous innovative biomaterials. Among the 3D printing methods, inkjet printing, so-called drop-on-demand (DOD) printing, stands out for its ability to construct biomaterials with superior spatial resolutions. However, its printing processes are still designed by trial and error due to a limited understanding of the ink behavior during the printing processes. This review discusses the current understanding of transport processes and hydrogel behaviors during inkjet printing for particulate-laden hydrogels. Specifically, we review the transport processes of water and particulates within hydrogel during ink formulation, jetting, and curing. Additionally, we examine current inkjet printing applications in fabricating engineered tissues, drug delivery devices, and advanced bioelectronics components. Finally, the challenges and opportunities for next-generation inkjet printing are also discussed. Highlights: • Inkjet printing recently emerged to construct hydrogels with particulates into advanced biomaterials and biomedical devices. • A fundamental understanding of intra and inter-drop transport processes begins to be established. • Challenges and opportunities for next-generation inkjet printing are also discussed. [ABSTRACT FROM AUTHOR]

Microneedle patches have been developed as favorable platforms for delivery systems, such as the locoregional application of therapeutic drugs, and implantation systems, such as electronic devices on visceral tissue surfaces. However, the challenge lies in finding materials that can achieve both biocompatibility and stable fixation on the target tissue. To address this issue, utilizing a biocompatible adhesive biomaterial allows the flat part of the patch to adhere as well, enabling double-sided adhesion for greater versatility. In this work, we propose an adhesive microneedle patch based on mussel adhesive protein (MAP) with enhanced mechanical strength via ultraviolet-induced polyacrylate crosslinking and Coomassie brilliant blue molecules. The strong wet tissue adhesive and biocompatible nature of engineered acrylated-MAP resulted in the development of a versatile wet adhesive microneedle patch system for in vivo usage. In a mouse tumor model, this microneedle patch effectively delivered anticancer drugs while simultaneously sealing the skin wound. Additionally, in an application of rat subcutaneous implantation, an electronic circuit was stably anchored using a double-sided wet adhesive microneedle patch, and its signal location underneath the skin did not change over time. Thus, the proposed acrylated-MAP-based wet adhesive microneedle patch system holds great promise for biomedical applications, paving the way for advancements in drug delivery therapeutics, tissue engineering, and implantable electronic medical devices. [Display omitted] • Wet adhesive microneedle patch was constructed using polyacrylated mussel protein. • Hardness of microneedle patches was enhanced by utilizing protein-binding molecules. • Locoregional drug delivery was performed in a prolonged and gradual manner. • Reliable and persistent fixation of electronic device for implantation was achieved. [ABSTRACT FROM AUTHOR]

In situ gelling systems represent a burgeoning paradigm in ocular drug administration, addressing intrinsic challenges posed by extant ocular formulations, such as compromised bioavailability and constraints in traversing the corneal barrier. This systematic review endeavours to comprehensively examine the contemporary landscape of research in this domain, focusing on the nuanced capabilities of in situ gelling systems to optimize drug delivery and enhance therapeutic outcomes, without much technological complexity. Employing a meticulous search strategy across diverse databases for publications and patents spanning the years 2015 to 2023 a total of 26 research papers and 14 patents meeting stringent inclusion criteria were identified. Synthesizing the collective insights derived from these investigations, it becomes evident that in situ gelling systems confer an ability to protract the residence time of formulations or active pharmaceutical ingredients (APIs) within the ocular milieu. This sustained presence engenders extended drug release kinetics, thereby fostering improved patient compliance and mitigating the proclivity for side effects attendant to frequent dosing. These salutary effects extend to diminished systemic drug absorption, augmented ocular bioavailability, and the prospect of reduced dosing frequencies, thereby amplifying patient adherence to therapeutic regimens. Intriguingly, the protective attributes of in situ gelling systems extend to the establishment of an ocular surface barrier, thereby abating the susceptibility to infections and inflammatory responses. In summation, this review underscores the auspicious potential of in situ gelling systems as a transformative approach to advancing ocular drug delivery, warranting sustained research endeavours and developmental initiatives for the betterment of global patient outcomes. [Display omitted] • In situ gels for ocular delivery offer simple alternative to conventional low performing drops • Various polymer and polymer combinations are used for in situ gelling, each with distinct mechanism and advantages. • Gelling upon application enhances drug retention and improves ocular bioavailability. • In situ gel-forming systems represent advanced ocular drug delivery, with enhanced therapeutic outcomes for eye disorders. • This review covers recent research and patents, focusing on ophthalmic applications of in situ gels. [ABSTRACT FROM AUTHOR]

Topical ophthalmic solutions (eye drops) are becoming increasingly popular in treating and preventing ocular diseases for their safety, noninvasiveness, and ease of handling. However, the static and dynamic barriers of eyes cause the extremely low bioavailability (<5%) of eye drops, making ocular therapy challenging. Thus, drug-eluting corneal contact lenses (DECLs) have been intensively investigated as a drug delivery device for their attractive properties, such as sustained drug release and improved bioavailability. In order to promote the clinical application of DECLs, multiple aspects, i.e., drug release and penetration, safety, and biocompatibility, of these drug delivery systems were thoroughly examined. In this review, we systematically discussed advances in DECLs, including types of preparation materials, drug-loading strategies, drug release mechanisms, strategies for penetrating ocular barriers, in vitro and in vivo drug delivery and penetration detection, safety, and biocompatibility validation methods, as well as challenges and future perspectives. [ABSTRACT FROM AUTHOR]

Microfluidics, a multidisciplinary field at the intersection of physics, engineering and biology is reshaping drug discovery. This review delves into its historical evolution, fundamental principles, components and manufacturing techniques. Microfluidics operates with precision, offering laminar flow, efficient mass transfer and scaling laws. Platforms like microscale cell culture systems, high-throughput screening techniques, lab-on-a-chip devices and organ-on-a-chip systems are driving advancements in disease modeling and pharmacokinetics. Despite challenges in device fabrication, regulation and costs, microfluidics promises an efficient, patient-centric future for drug discovery. Collaborative innovation can unlock its potential, making drug development faster, more precise and accessible. Microfluidics stands as a transformative force with the potential to revolutionize the drug development process. [ABSTRACT FROM AUTHOR]

The interface between material science and ophthalmic medicine is witnessing significant advances with the introduction of biopolymers in medical device fabrication. This review discusses the impact of biopolymers on the development of ophthalmic devices, such as intraocular lenses, stents, and various prosthetics. Biopolymers are emerging as superior alternatives due to their biocompatibility, mechanical robustness, and biodegradability, presenting an advance over traditional materials with respect to patient comfort and environmental considerations. We explore the spectrum of biopolymers used in ophthalmic devices and evaluate their physical properties, compatibility with biological tissues, and clinical performances. Specific applications in oculoplastic and orbital surgeries, hydrogel applications in ocular therapeutics, and polymeric drug delivery systems for a range of ophthalmic conditions were reviewed. We also anticipate future directions and identify challenges in the field, advocating for a collaborative approach between material science and ophthalmic practice to foster innovative, patient-focused treatments. This synthesis aims to reinforce the potential of biopolymers to improve ophthalmic device technology and enhance clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: Drug delivery from a drug-loaded device into an adjacent tissue is a complicated process involving drug transport through diffusion and advection, coupled with drug binding kinetics responsible for drug uptake in the tissue. This work presents a theoretical model to predict drug delivery from a device into a multilayer tissue, assuming linear reversible drug binding in the tissue layers. Methods: The governing mass conservation equations based on diffusion, advection and drug binding in a multilayer cylindrical geometry are written, and solved using Laplace transformation. The model is used to understand the impact of various non-dimensional parameters on the amounts of bound and unbound drug concentrations as functions of time. Results: Good agreement for special cases considered in past work is demonstrated. The effect of forward and reverse binding reaction rates on the multilayer drug binding process is studied in detail. The effect of the nature of the external boundary condition on drug binding and drug loss is also studied. For typical parameter values, results indicate that only a small fraction of drug delivered binds in the tissue. Additionally, the amount of bound drug rises rapidly with time due to early dominance of the forward reaction, reaches a maxima and then decays due to the reverse reaction. Conclusions: The general model presented here can account for other possible effects such as drug absorption within the device. Besides generalizing past work on drug delivery modeling, this work also offers analytical tools to understand and optimize practical drug delivery devices. [ABSTRACT FROM AUTHOR]

Summary: Healthcare applications with the Internet of Things (IoT) are often safety‐critical, thus, require extensive testing. Such applications are often connected to smart medical devices from various vendors. System‐level testing of such applications requires test infrastructures physically integrating medical devices, which is time and monetary‐wise expensive. Moreover, applications continuously evolve, for example, introducing new devices and users and updating software. Nevertheless, a test infrastructure enabling testing with a few devices is insufficient for testing healthcare IoT systems, hence compromising their dependability. In this paper, we propose a model‐based approach for the creation and operation of digital twins (DTs) of medicine dispensers as a replacement for physical devices to support the automated testing of IoT applications at scale. We evaluate our approach with an industrial IoT system with medicine dispensers in the context of Oslo City and its industrial partners, providing healthcare services to its residents. We study the fidelity of DTs in terms of their functional similarities with their physical counterparts: medicine dispensers. Results show that the DTs behave more than 92% similar to the physical medicine dispensers, providing a faithful replacement for the dispenser. [ABSTRACT FROM AUTHOR]

The digital light processing (DLP) printer has proven to be effective in biomedical and pharmaceutical applications, as its printing method does not induce shear and a strong temperature on the resin. In addition, the DLP printer has good resolution and print quality, which makes it possible to print complex structures with a customized shape, being used for various purposes ranging from jewelry application to biomedical and pharmaceutical areas. The big disadvantage of DLP is the lack of a biocompatible and non-toxic resin on the market. To overcome this limitation, an ideal resin for biomedical and pharmaceutical use is needed. The resin must have appropriate properties, so that the desired format is printed when with a determined wavelength is applied. Thus, the aim of this work is to bring the basic characteristics of the resins used by this printing method and the minimum requirements to start printing by DLP for pharmaceutical and biomedical applications. The DLP method has proven to be effective in obtaining pharmaceutical devices such as drug delivery systems. Furthermore, this technology allows the printing of devices of ideal size, shape and dosage, providing the patient with personalized treatment. [ABSTRACT FROM AUTHOR]

The drug detection technology plays a pivotal role in the domains of pharmaceutical regulation and law enforcement. In this study, we introduce a method that combines thermal desorption corona discharge ionization (TD-CDI) with mass spectrometry for efficient drug detection. The TD-CDI module, characterized by its compact and simple design, enables the separation of analytes within seconds and real-time presentation of one or two analyte peaks on the mass spectrum most of the time, which reduces matrix interference and improves detection performance. Through experimental investigation, we studied the characteristics of TD-CDI for analyte separation and detection, even with the same mass number, and optimized the TD-CDI approach. TD-CDI-MS was employed for the rapid detection of drugs in various traditional medicine, food products, and human samples. Additionally, by utilizing TD-CDI for segmented hair direct analysis, it becomes possible to trace the drug usage cycle of individuals. This underscores the feasibility of the proposed analytical method within the realm of drug detection. [ABSTRACT FROM AUTHOR]

Herein, a borophene/zinc oxide (BZ) nanocomposite is synthesized through a straightforward one‐step solvothermal process, avoiding the need for any rigorous reducing agent. The BZ nanocomposites are introduced into semi‐interpenetrating polymer networks to form hydrogels via in situ UV triggered free radical gelation during three‐dimensional (3D) microextrusion printing. The hydrogels exhibit mechanical robustness, high compressibility, pH sensitivity, and microporosity. The diffusion behavior of the hydrogel shows a combination of swelling and molecular chain relaxation based on its water uptake kinetics. Hydrogels are tested in rigorous pH environments over multiple cycles to ensure structural integrity. The rheological assessment of the hydrogels proves their high elasticity. The uniaxial mechanical properties support its mechanical toughness and zero permanent set resulting elastomeric soft matrix. The cyclic compression test up to 100 cycles has negligible data deviations in calculating compression moduli (≈24 kPa). The hydrogels are non‐toxic and found to be effective bactericidal materials for both Gram‐positive and Gram‐negative bacteria. The hydrogel demonstrates pH‐responsive time‐dependent payload release behavior, suggesting its potential as a soft matrix drug carrier in biomedical research. To the best of the authors knowledge, this is the first report of BZ‐based soft biomaterial with antibacterial properties serving as an excellent controlled drug delivery device. [ABSTRACT FROM AUTHOR]

The eye's complex anatomical structures present formidable barriers to effective drug delivery across a range of ocular diseases, from anterior to posterior segment pathologies. Emerging as a promising solution to these challenges, nanotechnology-based platforms—including but not limited to liposomes, dendrimers, and micelles—have shown the potential to revolutionize ophthalmic therapeutics. These nanocarriers enhance drug bioavailability, increase residence time in targeted ocular tissues, and offer precise, localized delivery, minimizing systemic side effects. Focusing on pediatric ophthalmology, particularly on retinoblastoma, this review delves into the recent advancements in functionalized nanosystems for drug delivery. Covering the literature from 2017 to 2023, it comprehensively examines these nanocarriers' potential impact on transforming the treatment landscape for retinoblastoma. The review highlights the critical role of these platforms in overcoming the unique pediatric eye barriers, thus enhancing treatment efficacy. It underscores the necessity for ongoing research to realize the full clinical potential of these innovative drug delivery systems in pediatric ophthalmology. [ABSTRACT FROM AUTHOR]

The escalating demand for enhanced therapeutic efficacy and reduced adverse effects in the pharmaceutical domain has catalyzed a new frontier of innovation and research in the field of pharmacy: novel drug delivery systems. These systems are designed to address the limitations of conventional drug administration, such as abbreviated half-life, inadequate targeting, low solubility, and bioavailability. As the disciplines of pharmacy, materials science, and biomedicine continue to advance and converge, the development of efficient and safe drug delivery systems, including biopharmaceutical formulations, has garnered significant attention both domestically and internationally. This article presents an overview of the latest advancements in drug delivery systems, categorized into four primary areas: carrier-based and coupling-based targeted drug delivery systems, intelligent drug delivery systems, and drug delivery devices, based on their main objectives and methodologies. Additionally, it critically analyzes the technological bottlenecks, current research challenges, and future trends in the application of novel drug delivery systems. [ABSTRACT FROM AUTHOR]

Aim: The field of targeted drug delivery is a rapidly advancing area of pharmaceutical research that focuses on optimizing the efficacy and safety of therapeutic agents. The primary goal is to enhance the concentration of a drug at its desired site of action while minimizing its presence in non-target areas. This selective accumulation not only improves the therapeutic outcomes but also significantly reduces the adverse effects often associated with drug therapies. By employing various carriers and mechanisms, targeted delivery systems can exert precise control over the rate and duration of drug release. This is particularly beneficial in chronic treatments where maintaining therapeutic drug levels is crucial. Moreover, the reduction in systemic exposure allows for lower dosages, which inversely correlates with increased bioavailability and drug effectiveness. Consequently, this leads to decreased healthcare costs and less frequent dosing schedules, improving patient compliance and quality of life. One innovative approach in this field is the utilization of nanotopography, which involves the replication of natural surface patterns at the nanometer scale onto drug carrier systems. These nature-inspired designs are not merely aesthetic; they play a functional role in modulating the interactions between the drug delivery vehicle and the biological target. For instance, surfaces mimicking the intricate patterns found in natural environments can influence cellular behavior, enhance adhesion, or even provide antimicrobial properties. Exploring the nuances of nanoengineered surfaces, this scholarly work reviews how nature-inspired topographies impact drug delivery and efficacy in pharmaceutical applications. It discusses the various methods of fabricating nanoscale topographies and their implications for drug delivery systems. The review highlights how these microscopic landscapes can affect biological functions such as cell adhesion, tissue barrier dynamics, and drug absorption rates. Surface modification techniques at the nanoscale are diverse, ranging from simple chemical treatments to sophisticated lithography and microcasting. These methods allow for the creation of specific patterns that can be tailored to enhance the performance of drug carriers. For example, In the context of drug delivery systems, the use of virus-inspired particles has facilitated drug absorption. These bioinspired designs enhance therapeutic outcomes. The role of nanotopography in drug delivery is multifaceted. It can facilitate the formation of bioadhesive interfaces that ensure the drug remains at the site of action for extended periods. This is particularly useful in mucosal drug delivery, where rapid clearance by bodily fluids can be a challenge. Additionally, the rearrangement of cellular barriers can be induced by these topographies, allowing for more efficient drug penetration in areas like the blood-brain barrier. Antimicrobial interfaces created through nanotopography can prevent the colonization of pathogens on drug delivery devices, reducing the risk of infections. This is especially important in implantable devices where biofilm formation can lead to device failure and serious health complications. In a nutshell, the review article provides a comprehensive overview of how nature-inspired nanotopography can revolutionize the field of drug delivery. By mimicking the wisdom of natural designs, pharmaceutical scientists can develop more effective and safer drug delivery systems that promise to improve therapeutic outcomes and patient care. [ABSTRACT FROM AUTHOR]

Magnetic microrobots, with their small size and agile maneuverability, are well-suited for navigating the intricate and confined spaces within the human body. In vivo cargo delivery within the context of microrobotics involves the use of microrobots to transport and administer drugs and cells directly to the targeted regions within a living organism. The principal aim is to enhance the precision, efficiency, and safety of therapeutic interventions. Despite their potential, there is a shortage of comprehensive reviews on the use of magnetic microrobots for in vivo cargo delivery from both research and engineering perspectives, particularly those published after 2019. This review addresses this gap by disentangling recent advancements in magnetic microrobots for in vivo cargo delivery. It summarizes their actuation platforms, structural designs, cargo loading and release methods, tracking methods, navigation algorithms, and degradation and retrieval methods. Finally, it highlights potential research directions. This review aims to provide a comprehensive summary of the current landscape of magnetic microrobot technologies for in vivo cargo delivery. It highlights their present implementation methods, capabilities, and prospective research directions. The review also examines significant innovations and inherent challenges in biomedical applications. [ABSTRACT FROM AUTHOR]

Hydrogels are a 3D polymer network capable of absorbing large amounts of water or biological fluids without dissolving, due to chemical or physical crosslinking. They are made from cellulose derivatives and are a promising research area for developing smart drug carriers in modern drug delivery systems. The present research aimed to synthesize hydrogels based on nanocellulose derivatives and evaluate their antibacterial activity. A crosslinker termed epichlorohydrin (ECH) was incorporated into Sengon plant cellulose to produce cellulose derivatives, specifically abietic nanocellulose (CAB). Hydrogels were synthesized from the nanocellulose derivatives. The hydrogels were characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM). The degree of substitution, release, and swelling tests, as well as antibacterial activity tests, were conducted. The results of the FTIR spectra revealed absorption between 1400 and 1600 cm-1, indicating a crosslinking process on the hydrogels. Furthermore, SEM cross-sectional observations demonstrated the formation of pores of various sizes. The hydrogel characterization results showed the impact of the preparation conditions, specifically the ECH concentration. The nanocellulose derivatives (NCAB): ECH concentration ratio varied between 1:0.5, 1:1, and 1:2. Based on the research results, the highest hydrogel swelling ratio was found in the CAB: ECH reaction conditions, which was 1:0.5. The findings of the present study demonstrated that modification by rosin esterification can result in hydrogels with desirable properties that can be employed for controlled drug delivery. Hydrogel from NCAB can inhibit the growth of E. coli bacteria in the weak category, but is moderate against S. aureus. [ABSTRACT FROM AUTHOR]

Combinatorial drug therapy has emerged as a critically important strategy in medical research and patient treatment and involves the use of multiple drugs in concert to achieve a synergistic effect. This approach can enhance therapeutic efficacy while simultaneously mitigating adverse side effects. However, the process of identifying optimal drug combinations, including their compositions and dosages, is often a complex, costly, and time-intensive endeavor. To surmount these hurdles, we propose a novel microfluidic device capable of simultaneously generating multiple drug concentration gradients across an interlinked array of culture chambers. This innovative setup allows for the real-time monitoring of live cell responses. With minimal effort, researchers can now explore the concentration-dependent effects of single-agent and combination drug therapies. Taking neural stem cells (NSCs) as a case study, we examined the impacts of various growth factors—epithelial growth factor (EGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF)—on the differentiation of NSCs. Our findings indicate that an overdose of any single growth factor leads to an upsurge in the proportion of differentiated NSCs. Interestingly, the regulatory effects of these growth factors can be modulated by the introduction of additional growth factors, whether singly or in combination. Notably, a reduced concentration of these additional factors resulted in a decreased number of differentiated NSCs. Our results affirm that the successful application of this microfluidic device for the generation of multi-drug concentration gradients has substantial potential to revolutionize drug combination screening. This advancement promises to streamline the process and accelerate the discovery of effective therapeutic drug combinations. [ABSTRACT FROM AUTHOR]

On‐demand controlled drug delivery is essential for the treatment of a wide range of chronic diseases. As the drug is released at the time when required, its efficacy is boosted and the side effects are minimized. However, so far, drug delivery devices often rely on the passive diffusion process for a sustained release, which is slow and uncontrollable. Herein, a miniaturized microfluidic device for wirelessly controlled ultrafast active drug delivery is presented, driven by an oscillating solid–liquid interface. The oscillation generates acoustic streaming in the drug reservoir, which opens an elastic valve to deliver the drug. High‐speed microscopy reveals the fast response of the valve on the order of 1 ms, which is more than three orders of magnitude faster than the start‐of‐the‐art. The amount of the released drug exhibits a linear relationship with the working time and the electric power applied to the ultrasonic resonator. The trigger of the release is wirelessly controlled via a magnetic field, and the system shows stable output in a continuous experiment for two weeks. The integrated system shows great promise as a long‐term controlled drug delivery implant for chronic diseases. [ABSTRACT FROM AUTHOR]

The advancements in the field of micro-robots for drug delivery systems have garnered considerable attention. In contrast to traditional drug delivery systems, which are dependent on blood circulation to reach their target, these engineered micro/nano robots possess the unique ability to navigate autonomously, thereby enabling the delivery of drugs to otherwise inaccessible regions. Precise drug delivery systems can improve the effectiveness and safety of synthetic lethality strategies, which are used for targeted therapy of solid tumors. MYCoverexpressing tumors show sensitivity to CDK1 inhibition. This study delves into the potential of Ro-3306 loaded magnetic-driven hydrogel micro-robots in the treatment of MYC-dependent osteosarcoma. Ro-3306, a specific inhibitor of CDK1, has been demonstrated to suppress tumor growth across various types of cancer. We have designed and fabricated this micro-robot, capable of delivering Ro-3306 precisely to tumor cells under the influence of a magnetic field, and evaluated its chemosensitizing effects, thereby augmenting the therapeutic efficacy and introducing a novel possibility for osteosarcoma treatment. The clinical translation of this method necessitates further investigation and validation. In summary, the Ro-3306-loaded magnetic-driven hydrogel microrobots present a novel strategy for enhancing the chemosensitivity of MYCdependent osteosarcoma, paving the way for new possibilities in future clinical applications. [ABSTRACT FROM AUTHOR]

Motivation: Drug combination therapies have shown promise in clinical cancer treatments. However, it is hard to experimentally identify all drug combinations for synergistic interaction even with high-throughput screening due to the vast space of potential combinations. Although a number of computational methods for drug synergy prediction have proven successful in narrowing down this space, fusing drug pairs and cell line features effectively still lacks study, hindering current algorithms from understanding the complex interaction between drugs and cell lines. Results: In this paper, we proposed a Permutable feature fusion network for Drug-Drug Synergy prediction, named PermuteDDS. PermuteDDS takes multiple representations of drugs and cell lines as input and employs a permutable fusion mechanism to combine drug and cell line features. In experiments, PermuteDDS exhibits state-of-the-art performance on two benchmark data sets. Additionally, the results on independent test set grouped by different tissues reveal that PermuteDDS has good generalization performance. We believed that PermuteDDS is an effective and valuable tool for identifying synergistic drug combinations. It is publicly available at https://github.com/littlewei-lazy/PermuteDDS. Scientific contribution: First, this paper proposes a permutable feature fusion network for predicting drug synergy termed PermuteDDS, which extract diverse information from multiple drug representations and cell line representations. Second, the permutable fusion mechanism combine the drug and cell line features by integrating information of different channels, enabling the utilization of complex relationships between drugs and cell lines. Third, comparative and ablation experiments provide evidence of the efficacy of PermuteDDS in predicting drug-drug synergy. [ABSTRACT FROM AUTHOR]

The design and development of a novel approach for the administration of a drug to the targeted area within the therapeutic dosage have been an ongoing progression for the last few decades. Developing biopolymer-based hydrogels as site-specific drug delivery devices is one such strategy gaining lots of attention. Herein, the present study reports the synthesis of novel, pH-responsive hydrogel using whole barley grain (Hordeum vulgare L.) and a biocompatible monomer, 2-acrylamido-2-methylpropanesulfonic acid through copolymerization method. The synthesized polymeric material has been characterized using various characterization methods and detailed swelling studies. After exploring the pH-responsive behavior and appreciable swelling at pH 7.4 (3925%) and pH 4.0 (3033%), suitable for blood-related ailments and anticancer studies, respectively. The synthesized superabsorbent has been explored as a drug delivery device using methylene blue (MB) as a drug against methemoglobinemia. MB dosage has been regulated within the therapeutic dosage (1–2 mg/kg) using synthesized material loaded at varied initial MB concentrations (50–500 ppm). The release mechanism has been determined using various kinetic models: zero-order, first-order, Higuchi, Korsmeyer–Peppas, and Hixson–Crowell. It was found that the release mechanism followed the Korsmeyer–Peppas model with 'n' values of 0.78 (500 ppm), 0.84 (300 ppm), 0.77 (100 ppm), 0.34 (50 ppm) at pH 7.4 and 0.69 (500 ppm), 0.86 (300 ppm), 0.73 (100 ppm) and 0.31 (50 ppm) at pH 4.0, respectively, at 37 °C in 7 h, which significantly depicted non-Fickian diffusion with controlled release of MB. [ABSTRACT FROM AUTHOR]

Purpose: Hollow-type microneedles (hMNs) are a promising device for the effective administration of drugs into intradermal sites. Complete insertion of the needle into the skin and administration of the drug solution without leakage must be achieved to obtain bioavailability or a constant effect. In the present study, several types of hMN with or without a rounded blunt tip micropillar, which suppresses skin deformation, around a hollow needle, and the effect on successful needle insertion and administration of a drug solution was investigated. Six different types of hMNs with needle lengths of 1000, 1300, and 1500 µm with or without a micropillar were used. Methods: Needle insertion and the disposition of a drug in rat skin were investigated. In addition, the displacement-force profile during application of hMNs was also investigated using a texture analyzer with an artificial membrane to examine needle factors affecting successful insertion and administration of a drug solution by comparing with in vivo results. Results: According to the results with the drug distribution of iodine, hMN1300 with a micropillar was able to successfully inject drug solution into an intradermal site with a high success rate. In addition, the results of displacement-force profiles with an artificial membrane showed that a micropillar can be effective for depth control of the injected solution as well as the prevention of contact between the hMN pedestal and the deformed membrane. Conclusion: In the present study, hMN1300S showed effective solution delivery into an intradermal site. In particular, a micropillar can be effective for depth control of the injected solution as well as preventing contact between the hMN pedestal and the deformed membrane. The obtained results will help in the design and development of hMNs that ensure successful injection of an administered drug. [ABSTRACT FROM AUTHOR]

Fungal keratitis (FK) is a dangerous corneal infection that is common in tropical and subtropical areas. Its incidence is extremely high, and ocular trauma and contact lenses can lead to FK, but its common treatment such as using topical antifungal eye drop instillation is often less effective because of several drawbacks of the drugs typically used, including limited ocular penetration, high frequency of dosing, poor biocompatibility, and the potential for severe drug reactions. Therefore, the development of novel drug delivery devices for the treatment of FK is urgent. The urgent need for novel drug delivery devices to treat FK has led to the development of several techniques, including nanoparticles (NPs), in situ forming hydrogels, contact lenses, and microneedles (MNs). However, it is important to note that the main mechanisms differ between these techniques. NPs can transport large amounts of drugs and be taken up by cells owing to their large surface area and small size. In situ forming hydrogels can significantly extend the residence time of drugs because of their strong adhesive properties. Contact lenses, with their comfortable shape and drug-carrying capacity, can also act as drug delivery devices. MNs can create channels in the cornea, bypassing its barrier and enhancing drug bioavailability. This article will go over novel medication delivery techniques for treating FK and make a conclusion about their advantages and limitations in anticipation to serve the best option for the individual therapy of FK. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery refers to a drug delivery route that delivers drugs through the skin to produce local or systemic therapeutic effects. In this work, we propose a parallel valveless piezoelectric micropump integrated with hollow microneedle array, which can be used in flexible wearable transdermal drug delivery systems. The device consists of two valveless piezoelectric micropump, a hollow microneedle array and an electrical control module. The main structure of micropump and the hollow microneedle array are fabricated using 3D printing technology. The valveless piezoelectric micropump adopts a parallel dualpump structure with asynchronous drive, which achieves a full forward flow at the outlet and reduces the influence of backflow on the stability of the system. In addition, the parallel dual‐pump structure proposed in this work can be extended to a multimicropump parallel structure. We hope to fabricate small‐size micropump arrays on flexible substrates and integrate them into flexible wearable transdermal drug delivery systems. [ABSTRACT FROM AUTHOR]

Chitosan (CS) can be extracted from waste fish scales through a series of chemical processes, including demineralization, deproteinization, and deacetylation. The biomaterial poly (acrylamide [AM]‐co‐acrylic acid [AA])/CS is a unique superabsorbent material synthesized through the free radical graft copolymerization method by using AM, AA, and CS powder. During synthesis, ammonium persulfate is used as an initiator, and N, N′‐methylene bisacrylamide is used as a cross‐linker. Scanning electron microscopy and Fourier transform infrared spectroscopy have been studied to know about the morphology and structure of the synthesized superabsorbent materials. The water absorbency of the material continuously increases from day 1 to day 30. The thermogravimetric analysis (TGA) and derivative thermogravimetry (DTG) of the superabsorbent material show adequate thermal stability. The X‐ray diffraction (XRD) analysis indicates that the synthesized biomaterial is virtually amorphous in nature. The percentage of biodegradability increases with time. The encapsulation efficiency of amoxicillin drugs is around 70%, which indicates that the biomaterial is highly efficient for drug release applications. The synthesized novel biomaterial is a low‐cost, eco‐friendly, and thermally stable hydrogel that can be effectively used in drug release applications. Highlights: Chitosan (CS)‐based hydrogels are highly pH‐sensitive towards drug release.The biodegradability and swelling behavior of the synthesized biomaterial were studied by adopting a suitable methodology.The novel material formed was characterized by using Fourier transform infrared spectroscopy, TGA, and Scanning electron microscopy. The encapsulation efficiency, kinetic study, and controlled drug release behavior of the amoxicillin drug were studied in solutions of simulated gastric fluid and phosphate‐buffered saline.The material developed in this study shows good performance in controlled drug delivery, and is therefore suitable for manufacturing medical devices used in drug delivery. [ABSTRACT FROM AUTHOR]

The overactive bladder is a condition characterized by a sudden urge to urinate, even with small volumes of urine present in the bladder. The current treatments available for this pathology consist on conservative approaches and the continuous administration of drugs, which when made by conventional methods has limitations related to the first pass metabolism, bioavailability, severe side effects, and low patient adherence to treatments, ultimately leading to low effectiveness. Within this context, the present work proposes the design, manufacture, and characterization of an intravesical implant for the treatment of overactive bladder pathology, using EVA copolymer as a matrix and oxybutynin as a drug. The fabrication of devices through two manufacturing techniques (extrusion and additive manufacturing by fused filament fabrication, FFF) and the evaluation of the implants through characterization tests was proposed. The usability and functionality were evaluated through simulated insertion of the device/prototype in a bladder model through catheter insertion tests. The safety and effectiveness of the devices was investigated from mechanical testing as well as drug release assays. Drug release assays presented a burst release in the first 24 h, followed by a release of 1.8 and 2.8 mg/d, totalizing 32 d. Mechanical tests demonstrated an increase in the stiffness of the specimens due to the addition of the drug, showing a change in maximum stress and strain at break. The released dose was higher than that usually presented when considering the oral administration route, showing the optimization of the development of this implant has the potential to improve the quality of life of patients with overactive bladder. [ABSTRACT FROM AUTHOR]

Cyclodextrin-based nanosponges (CDNSs) are complex macromolecular structures composed of individual cyclodextrins (CDs) and nanochannels created between cross-linked CD units and cross-linkers. Due to their unique structural and physicochemical properties, CDNSs can possess even more beneficial pharmaceutical features than single CDs. In this comprehensive review, various aspects related to CDNSs are summarized. Particular attention was paid to overviewing structural properties, methods of synthesis, and physicochemical analysis of CDNSs using various analytical methods, such as DLS, PXRD, TGA, DSC, FT-IR, NMR, and phase solubility studies. Also, due to the significant role of CDNSs in pharmaceutical research and industry, aspects such as drug loading, drug release studies, and kinetics profile evaluation of drug–CDNS complexes were carefully reviewed. The aim of this paper is to find the relationships between the physicochemical features and to identify crucial characteristics that are influential for using CDNSs as convenient drug delivery systems. [ABSTRACT FROM AUTHOR]