Modeling of Dissolving Microneedle-Based Transdermal Drug Delivery: Effects of Dynamics of Polymers in Solution.

Dissolving microneedle (DMN)-assisted transdermal drug delivery (TDD) has received attention from the scientific community in recent years due to its ability to control the rate of drug delivery through its design, the choice of polymers, and its composition. The dissolution of the polymer depends strongly on the polymer-solvent interaction and polymer physics. Here, we developed a mathematical model based on the physicochemical parameters of DMNs and polymer physics to determine the drug release profiles. An annular gap width is defined when the MN is inserted in the skin, accumulating interstitial fluid (ISF) from the surrounding skin and acting as a boundary layer between the skin and the MN. Poly(vinylpyrrolidone) (PVP) is used as a model dissolving polymer, and ceftriaxone is used as a representative drug. The model agrees well with the literature data for ex vivo permeation studies, along with the percent height reduction of the MN. Based on the suggested mathematical model, when loading 0.39 mg of ceftriaxone, the prediction indicates that approximately 93% of the drug will be cleared from the bloodstream within 24 h. The proposed modeling strategy can be utilized to optimize drug transport behavior using DMNs.

Innovations in Biosensor Technologies for Healthcare Diagnostics and Therapeutic Drug Monitoring: Applications, Recent Progress, and Future Research Challenges.

This comprehensive review delves into the forefront of biosensor technologies and their critical roles in disease biomarker detection and therapeutic drug monitoring. It provides an in-depth analysis of various biosensor types and applications, including enzymatic sensors, immunosensors, and DNA sensors, elucidating their mechanisms and specific healthcare applications. The review highlights recent innovations such as integrating nanotechnology, developing wearable devices, and trends in miniaturisation, showcasing their transformative potential in healthcare. In addition, it addresses significant sensitivity, specificity, reproducibility, and data security challenges, proposing strategic solutions to overcome these obstacles. It is envisaged that it will inform strategic decision-making, drive technological innovation, and enhance global healthcare outcomes by synthesising multidisciplinary insights.

Applications of Machine Learning (ML) and Mathematical Modeling (MM) in Healthcare with Special Focus on Cancer Prognosis and Anticancer Therapy: Current Status and Challenges.

The use of data-driven high-throughput analytical techniques, which has given rise to computational oncology, is undisputed. The widespread use of machine learning (ML) and mathematical modeling (MM)-based techniques is widely acknowledged. These two approaches have fueled the advancement in cancer research and eventually led to the uptake of telemedicine in cancer care. For diagnostic, prognostic, and treatment purposes concerning different types of cancer research, vast databases of varied information with manifold dimensions are required, and indeed, all this information can only be managed by an automated system developed utilizing ML and MM. In addition, MM is being used to probe the relationship between the pharmacokinetics and pharmacodynamics (PK/PD interactions) of anti-cancer substances to improve cancer treatment, and also to refine the quality of existing treatment models by being incorporated at all steps of research and development related to cancer and in routine patient care. This review will serve as a consolidation of the advancement and benefits of ML and MM techniques with a special focus on the area of cancer prognosis and anticancer therapy, leading to the identification of challenges (data quantity, ethical consideration, and data privacy) which are yet to be fully addressed in current studies.

Anti-Obesity Drug Delivery Systems: Recent Progress and Challenges.

Obesity has reached an epidemic proportion in the last thirty years, and it is recognized as a major health issue in modern society now with the possibility of serious social and economic consequences. By the year 2030, nearly 60% of the global population may be obese or overweight, which emphasizes a need for novel obesity treatments. Various traditional approaches, such as pharmacotherapy and bariatric surgery, have been utilized in clinical settings to treat obesity. However, these methods frequently show the possibility of side effects while remaining ineffective. There is, therefore, an urgent need for alternative obesity treatments with improved efficacy and specificity. Polymeric materials and chemical strategies are employed in emerging drug delivery systems (DDSs) to enhance therapy effectiveness and specificity by stabilizing and controlling the release of active molecules such as natural ingredients. Designing DDSs is currently a top priority research objective with an eye towards creating obesity treatment approaches. In reality, the most recent trends in the literature demonstrate that there are not enough in-depth reviews that emphasize the current knowledge based on the creation and design of DDSs for obesity treatment. It is also observed in the existing literature that a complex interplay of different physical and chemical parameters must be considered carefully to determine the effectiveness of the DDSs, including microneedles, for obesity treatment. Additionally, it is observed that these properties depend on how the DDS is synthesized. Although many studies are at the animal-study stage, the use of more advanced DDS techniques would significantly enhance the development of safe and efficient treatment approaches for obese people in the future. Considering these, this review provides an overview of the current anti-obesity treatment approaches as well as the conventional anti-obesity therapeutics. The article aims to conduct an in-depth discussion on the current trends in obesity treatment approaches. Filling in this knowledge gap will lead to a greater understanding of the safest ways to manage obesity.

Potential of Microneedle Systems for COVID-19 Vaccination: Current Trends and Challenges.

To prevent the coronavirus disease 2019 (COVID-19) pandemic and aid restoration to prepandemic normality, global mass vaccination is urgently needed. Inducing herd immunity through mass vaccination has proven to be a highly effective strategy for preventing the spread of many infectious diseases, which protects the most vulnerable population groups that are unable to develop immunity, such as people with immunodeficiencies or weakened immune systems due to underlying medical or debilitating conditions. In achieving global outreach, the maintenance of the vaccine potency, transportation, and needle waste generation become major issues. Moreover, needle phobia and vaccine hesitancy act as hurdles to successful mass vaccination. The use of dissolvable microneedles for COVID-19 vaccination could act as a major paradigm shift in attaining the desired goal to vaccinate billions in the shortest time possible. In addressing these points, we discuss the potential of the use of dissolvable microneedles for COVID-19 vaccination based on the current literature.

Biocompatibility of hydroxyethyl cellulose/glycine/RuO2 composite scaffolds for neural-like cells.

Fabrication of scaffolds for nerve regeneration is one of the most challenging topics in regenerative medicine at the moment, which is also interlinked with the development of biocompatible substrates for cells growth. This work is targeted towards the development of green biomaterial composite scaffolds for nerve cell culture applications. Hybrid scaffolds of hydroxyethyl cellulose/glycine (HEC/Gly) composite doped with different concentrations of green ruthenium oxide (RuO2) were synthesized and characterized via a combination of different techniques. X-rays diffraction (XRD) and differential scanning calorimetry (DSC) analyses showed a crystalline nature for all the samples with noticeable decrease in the peak intensity of the fabricated scaffolds as compared to that for pure glycine. Fourier transform infrared spectroscopy (FTIR) tests revealed an increase in the vibrational bands of the synthesized RuO2 containing scaffolds which are related to the functional groups of the natural plant extract (Aspalathuslinearis) used for RuO2 nanoparticles (NPs) synthesis. Scanning electron microscopy (SEM) results revealed a 3D porous structure of the scaffolds with variant features attributed to the concentration of RuO2 NPs in the scaffold. The compressive test results recorded an enhancement in mechanical properties of the fabricated scaffolds (up to 8.55 MPa), proportionally correlated to increasing the RuO2 NPs concentration in HEC/Gly composite scaffold. Our biocompatibility tests revealed that the composite scaffolds doped with 1 and 2 ml of RuO2 demonstrated the highest proliferation percentages (152.2 and 135.6%) compared to control. Finally, the SEM analyses confirmed the impressive cells attachments and differentiation onto the scaffold surfaces as evidenced by the presence of many neuron-like cells with apparent cell bodies and possessing few short neurite-like processes. The presence of RuO2 and glycine was due to their extraordinary biocompatibility due to their cytoprotective and regenerative effects. Therefore, we conclude that these scaffolds are promising for accommodation and growth of neural-like cells.

Novel zinc-silver nanocages for drug delivery and wound healing: Preparation, characterization and antimicrobial activities.

Metal organic framework (MOF)-nanocages (MOF-NCs) in the form of zinc-based nanoparticles (NPs) were synthesized as drug carriers for the purpose of wound healing. The prepared NCs (single and bi-metallic with silver-MOF) were based on zinc and they were loaded with ascorbic acid (vitamin C) as a model drug which accelerates wound healing. The NCs were then investigated by several characterization techniques such as XRD, TEM, FTIR and BET surface area. Furthermore, the release behavior of the loaded ascorbic acid from the developed NCs was measured in phosphate buffer solution (PBS). NCs antibacterial activity was tested against strain of gram-positive bacteria (Staphylococcus aureus ATCC- 29213, Streptococcus pyogenes ATCC-19615 and Bacillus subtilis ATCC-6633), gram-negative bacteria strain (Pseudomonas aeruginosaATCC-27853and Escherichia coli ATCC-25922) and fungi (Candida albicans ATCC-10231).The physicochemical features of the NCs were confirmed by the results obtained from XRD and FTIR measurements. The particle size of the NCs was confirmed to be in the range of 30-50 nm. Prolonged drug release that was combined with impressive antibacterial activities, and good wound healing rates were also recognized for the zinc based NCs in comparison to commonly used Ag NPs. It is concluded that the current NCs are potentially suitable for wound healing and drug delivery applications.

Advancements in modification of membrane materials over membrane separation for biomedical applications-Review.

A comprehensive overview of various modifications carried out on polymeric membranes for biomedical applications has been presented in this review paper. In particular, different methods of carrying out these modifications have been discussed. The uniqueness of the review lies in the sense that it discusses the surface modification techniques traversing the timeline from traditionally well-established technologies to emerging new techniques, thus giving an intuitive understanding of the evolution of surface modification techniques over time. A critical comparison of the advantages and pitfalls of commonly used traditional and emerging surface modification techniques have been discussed. The paper also highlights the tuning of specific properties of polymeric membranes that are critical for their increased applications in the biomedical industry specifically in drug delivery, along with current challenges faced and where the future potential of research in the field of surface modification of membranes.

Improving the assessment of polluted sites using an integrated bio-physico-chemical monitoring framework.

Soil - water pollution resulting from anthropogenic activities is a growing concern internationally. Effective monitoring techniques play a crucial role in the detection, prevention, and remediation of polluted sites. Current pollution monitoring practices in many geographical locations are primarily based on physico-chemical assessments which do not always reflect the potential toxicity of contaminant 'cocktails' and harmful chemicals not screened for routinely. Biomonitoring provides a range of sensitive techniques to characterise the eco-toxicological effects of chemical contamination. The bioavailability of contaminants, in addition to their effects on organisms at the molecular, cellular, individual, and community level allows the characterisation of the overall health status of polluted sites and ecosystems. Quantifying bioaccumulation, changes to community structure, faunal morphology, behavioural, and biochemical responses are standard procedures employed in biomonitoring studies in many High-Income Countries (HICs). This review highlights the need to integrate biomonitoring tools alongside physico-chemical monitoring techniques by using 'effect-based' tools to provide more holistic information on the ecological impairment of soil-water systems. This paper considers the wider implementation of biomonitoring methods in Low to Middle Income Countries (LMICs) and their significance in pollution investigations and proposes an integrated monitoring framework that can identify toxicity drivers by utilising 'effect-based' and 'risk-based' monitoring approaches.

Oil Spill Sorber Based on Extrinsically Magnetizable Porous Geopolymer.

Environmental impacts are increasingly due to the human polluting activities. Therefore, there is a need to develop technologies capable of removing contamination and driving the impacted environment as close as possible to its inherent characteristics. One of the major problems still faced is the spill of oil into water. Therefore, to solve the environmental problem, this work shows the use of magnetically modified geopolymer materials as an oil remover from water with a magnet's aid. The results obtained were outstanding since the average intrinsic oil removal capability (IORC) was 150 g/g. The presented IORC is the largest found in the materials produced by our research group, constituting an extremely encouraging result, mainly because of the ease of preparing the magnetic geopolymer system. Furthermore, the low cost of production and the material's capability to be reused as filler of polymer or even cementitious matrices allows us to project that this nanocomposite can be widely used, constituting an economically viable alternative for more efficient environmental recovery processes.

Effects of Scaffold Pore Morphologies on Glucose Transport Limitations in Hollow Fibre Membrane Bioreactor for Bone Tissue Engineering: Experiments and Numerical Modelling.

In the current research, three electrospun polycaprolactone (PCL) scaffolds with different pore morphology induced by changing the electrospinning parameters, spinning time and rate, have been prepared in order to provide a fundamental understanding on the effects pore morphology have on nutrient transport behaviour in hollow fibre membrane bioreactor (HFMB). After determining the porosity of the scaffolds, they were investigated for glucose diffusivity using cell culture media (CCM) and distilled water in a diffusion cell at 37 °C. The scanning electron microscope (SEM) images of the microstructure of the scaffolds were analysed further using ImageJ software to determine the porosity and glucose diffusivity. A Krogh cylinder model was used to determine the glucose transport profile with dimensionless variables within the HFMB. The paper discusses the roles of various dimensionless numbers (e.g., Péclet and Damköhler numbers) and non-dimensional groups of variables (e.g., non-dimensional fibre radius) on determining glucose concentration profiles, especially in the scaffold region. A negative linear relationship between glucose diffusivities across PCL scaffolds and the minimum glucose concentrations (i.e., concentration on the outer fibre edge on the outlet side (at z = 1 and r = 3.2) was also found. It was shown that the efficiency of glucose consumption improves with scaffolds of higher diffusivities. The results of this study are expected to help in optimizing designs of HFMB as well as carry out more accurate up scaling analyses for the bioreactor.

Nanomaterials for Biomedical Applications: Production, Characterisations, Recent Trends and Difficulties.

Designing of nanomaterials has now become a top-priority research goal with a view to developing specific applications in the biomedical fields. In fact, the recent trends in the literature show that there is a lack of in-depth reviews that specifically highlight the current knowledge based on the design and production of nanomaterials. Considerations of size, shape, surface charge and microstructures are important factors in this regard as they affect the performance of nanoparticles (NPs). These parameters are also found to be dependent on their synthesis methods. The characterisation techniques that have been used for the investigation of these nanomaterials are relatively different in their concepts, sample preparation methods and obtained results. Consequently, this review article aims to carry out an in-depth discussion on the recent trends on nanomaterials for biomedical engineering, with a particular emphasis on the choices of the nanomaterials, preparation methods/instruments and characterisations techniques used for designing of nanomaterials. Key applications of these nanomaterials, such as tissue regeneration, medication delivery and wound healing, are also discussed briefly. Covering this knowledge gap will result in a better understanding of the role of nanomaterial design and subsequent larger-scale applications in terms of both its potential and difficulties.

Multifunctional magnetite nanoparticles for drug delivery: Preparation, characterisation, antibacterial properties and drug release kinetics.

Multifunctional nanoparticles (NPs) with magnetic (M) and antibacterial properties were prepared for drug delivery purposes by a method involving co-precipitation synthesis. Partial and complete substitutions of ferrous ions (Fe2+) by copper ions (Cu2+) were carried out for the preparation of the magnetite NPs, which are designated as Cu0.5M and CuM, respectively, in this work. In addition, chitosan and ciprofloxacin were hybridized with the NPs from the previous step to achieve multifunctional properties. XRD, TEM, SEM/EDAX, VSM and FTIR were subsequently employed to characterize various properties of the prepared NPs, namely, crystallinity, nanostructure (size), particle morphology, elemental mapping, magnetic strength and chemical composition. Antibacterial properties of the NPs were tested against Bacillus cereus (Gram-positive bacteria), Escherichia coli (Gram-negative bacteria) and Candida albicans (yeast). Efficiency of the ciprofloxacin release was also studied for the drug-loaded NPs. It is demonstrated that the obtained NPs possess mixed phases with crystalline structures that are affected by the degree of Cu ion substitution (5-10 nm (M), 2.5-3.5 nm (Cu0.5M) and 11-16 nm (CuM)). Saturation magnetization values of the NPs were recorded as 38.7, 3.5 and 1.3 emu/g, respectively. It was also found that the introduction of Cu ions in the NP samples improved the significance of their antibacterial activity, especially against Escherichia coli. Chitosan and ciprofloxacin were found to have stronger effects against Bacillus cereus and Escherichia coli and lesser effects against Candida albicans. However, the samples containing chitosan, ciprofloxacin and the higher Cu ion concentration exhibited strong influence against Candida albicans. During a study period of 30-days, the amounts of released drug from the tested NPs were 85, 26 and 20% of the originally loaded amount, respectively. Owing to the findings in this paper, the developed NPs are considered to have good potential for drug delivery applications and to study them further such as in pre-clinical studies.

Pharmaceutical Particulates and Membranes for the Delivery of Drugs and Bioactive Molecules.

The delivery of drugs and bioactive molecules using pharmaceutical particulates and membranes are of great significance for various applications such as the treatment of secondary infections, cancer treatment, skin regeneration, orthopedic applications and others [...].

Recent progress in the fabrication techniques of 3D scaffolds for tissue engineering.

Significant advances have been made in the field of tissue engineering (TE), especially in the synthesis of three-dimensional (3D) scaffolds for replacing damaged tissues and organs in laboratory conditions. However, the gaps in knowledge in exploiting these techniques in preclinical trials and beyond and, in particular, in practical scenarios (e.g., replacing real body organs) have not been discussed well in the existing literature. Furthermore, it is observed in the literature that while new techniques for the synthesis of 3D TE scaffold have been developed, some of the earlier techniques are still being used. This implies that the advantages offered by a more recent and advanced technique as compared to the earlier ones are not obvious, and these should be discussed in detail. For example, one needs to be aware of the reason, if any, behind the superiority of traditional electrospinning technique over recent advances in 3D printing technique for the production of 3D scaffolds given the popularity of the former over the latter, indicated by the number of publications in the respective areas. Keeping these points in mind, this review aims to demonstrate the ongoing trend in TE based on the scaffold fabrication techniques, focusing mostly, on the two most widely used techniques, namely, electrospinning and 3D printing, with a special emphasis on preclinical trials and beyond. In this context, the advantages, disadvantages, flexibilities and limitations of the relevant techniques (electrospinner and 3D printer) are discussed. The paper also critically analyzes the applicability, restrictions, and future demands of these techniques in TE including their applications in generating whole body organs. It is concluded that combining these knowledge gaps with the existing body of knowledge on the preparation of laboratory scale 3D scaffolds, would deliver a much better understanding in the future for scientists who are interested in these techniques.

Nanoparticle- and Nanoporous-Membrane-Mediated Delivery of Therapeutics.

Pharmaceutical particulates and membranes possess promising prospects for delivering drugs and bioactive molecules with the potential to improve drug delivery strategies like sustained and controlled release. For example, inorganic-based nanoparticles such as silica-, titanium-, zirconia-, calcium-, and carbon-based nanomaterials with dimensions smaller than 100 nm have been extensively developed for biomedical applications. Furthermore, inorganic nanoparticles possess magnetic, optical, and electrical properties, which make them suitable for various therapeutic applications including targeting, diagnosis, and drug delivery. Their properties may also be tuned by controlling different parameters, e.g., particle size, shape, surface functionalization, and interactions among them. In a similar fashion, membranes have several functions which are useful in sensing, sorting, imaging, separating, and releasing bioactive or drug molecules. Engineered membranes have been developed for their usage in controlled drug delivery devices. The latest advancement in the technology is therefore made possible to regulate the physico-chemical properties of the membrane pores, which enables the control of drug delivery. The current review aims to highlight the role of both pharmaceutical particulates and membranes over the last fifteen years based on their preparation method, size, shape, surface functionalization, and drug delivery potential.

Novel polysaccharide hybrid scaffold loaded with hydroxyapatite: Fabrication, bioactivity, and in vivo study.

The main goal of this study was to produce a novel porous scaffold for rapid in vivo bone healing behavior. Lyophilization technique was used to produce this highly porous hybrid scaffold from Na-alginate (S) and hydroxyethylcellulose (HEC) impregnated with different concentration of hydroxyapatite (HA). After cross-linking the scaffolds, their incubation was carried out in simulated body fluid (SBF) for 4 weeks at 37 °C to investigate their bioactivity. A number of techniques were employed (e.g., XRD, FTIR, SEM, EDX, and texture analyzer) to characterize the designed scaffolds. It was observed that the mechanical properties of the scaffolds increase deformation energy (182 ±â€¯16 J/m3) and rigidity gradient (19.44 ±â€¯0.85 Pa) after loading with HA. Furthermore, the scaffolds were implanted in femur critical size defects (2 mm) of adult male Wistar rats for 6 weeks. In vitro and in vivo analyses demonstrated impressive bioactivity and biocompatibility for the prepared scaffolds, especially those containing HA. Based on the obtained results we conclude that the designed scaffolds are promising solutions for bone regeneration applications.

Influence of Niobium Pentoxide Particulates on the Properties of Brushite/Gelatin/Alginate Membranes.

Novel nonporous membranes were prepared by impregnating brushite and niobium pentoxide (Nb2O5) into a gelatin/alginate matrix. The physicochemical properties, morphology, and mechanical properties of the prepared membranes were characterized using X-ray diffractometer, FTIR spectroscopy, scanning electron microscopy, transmission electron microscopy, and universal testing machine, respectively. Swelling ability of the prepared membranes was determined in distilled water. The surfaces of the membranes were characterized by means of FTIR spectroscopy and scanning electron microscopy coupled with energy dispersive x-ray spectroscopy after submersion in simulated body fluid up to 15 days. Moreover, the calcium and phosphorus ion concentrations in the simulated body fluid were measured using an UV spectrophotometer. The in vitro drug release and the release mechanism of a model antibiotic, namely, ciprofloxacin (CFX), were tested in phosphate-buffered saline for 15 days. The antibacterial activities of the CFX-loaded membranes were tested against known microorganisms. The physicochemical properties, morphology, mechanical properties, and swelling ability of the prepared membranes were found to be dependent on the presence of Nb2O5 allowing control of their properties. For example, the Nb2O5-loaded membranes exhibited a higher in vitro bioactivity and slower drug release compared to those of Nb2O5-free membranes. The CFX-loaded membranes also exhibited an excellent inhibition zones against the selected microorganisms. Overall, the prepared membranes have been found to be very promising for use in bone substitute applications.

Microneedle-assisted transdermal delivery of Zolmitriptan: effect of microneedle geometry, in vitro permeation experiments, scaling analyses and numerical simulations.

OBJECTIVE: The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation enhancement of Zolmitriptan (ZMT). METHODS: Two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 0.9, 1.2 and 1.5 mm lengths) and laboratory fabricated polymeric MNs (PM) of 0.6 mm length were employed. In the case of PMs, arrays were applied thrice at different places within a 1.77 cm2 skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Scaling analyses was done using dimensionless parameters like concentration of ZMT (Ct/Cs), thickness (h/L) and surface area of the skin (Sa/L2). RESULTS: Micro-injection molding technique was employed to fabricate PM. Histological studies revealed that the PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 3.17- and 3.65-fold increase in ZMT flux values were observed with 1.5 mm ADM and PM-3 applications when compared to the passive studies. Good correlations were observed between different dimensionless parameters with scaling analyses. Numerical simulations, using MATLAB and COMSOL software, based on experimental data and histological images provided information regarding the ZMT skin distribution after MN application. DISCUSSION: Both from experimental studies and simulations, it was inferred that PM were more effective in enhancing the transdermal delivery of ZMT when compared to ADM. CONCLUSIONS: The study suggests that MN application enhances the ZMT transdermal permeation and the geometrical parameters of MNs play an important role in the degree of such enhancement.

Lidocaine-loaded fish scale-nanocellulose biopolymer composite microneedles.

Microneedle (MN) technology has emerged as an effective drug delivery system, and it has tremendous potential as a patient friendly substitute for conventional methods for transdermal drug delivery (TDD). In this paper, we report on the preparation of lidocaine-loaded biodegradable microneedles, which are manufactured from fish scale-derived collagen. Lidocaine, a common tissue numbing anaesthetic, is loaded in these microneedles with an aim of delivering the drug with controlled skin permeation. Evaluation of lidocaine permeation in porcine skin has been successfully performed using Franz diffusion cell (FDC) which has shown that the drug permeation rate increases from 2.5 to 7.5% w/w after 36 h and pseudo steady state profile is observed from 5.0 to 10.0% w/w lidocaine-loaded microneedle. Swelling experiments have suggested that the microneedles have negligible swellability which implies that the patch would stick to the tissue when inserted. The experiments on MN dissolution have depicted that the lidocaine loaded in the patch is lower than the theoretical loading, which is expected as there can be losses of the drug during initial process manufacture.