The use of antifungal drugs started in the 1950s with polyenes nystatin, natamycin and amphotericin B-deoxycholate (AmB). Until the present day, AmB has been considered to be a hallmark in the treatment of invasive systemic fungal infections. Nevertheless, the success and the use of AmB were associated with severe adverse effects which stimulated the development of new antifungal drugs such as azoles, pyrimidine antimetabolite, mitotic inhibitors, allylamines and echinochandins. However, all of these drugs presented one or more limitations associated with adverse reactions, administration route and more recently the development of resistance. To worsen this scenario, there has been an increase in fungal infections, especially in invasive systemic fungal infections that are particularly difficult to diagnose and treat. In 2022, the World Health Organization (WHO) published the first fungal priority pathogens list, alerting people to the increased incidence of invasive systemic fungal infections and to the associated risk of mortality/morbidity. The report also emphasized the need to rationally use existing drugs and develop new drugs. In this review, we performed an overview of the history of antifungals and their classification, mechanism of action, pharmacokinetic/pharmacodynamic (PK/PD) characteristics and clinical applications. In parallel, we also addressed the contribution of fungi biology and genetics to the development of resistance to antifungal drugs. Considering that drug effectiveness also depends on the mammalian host, we provide an overview on the roles of therapeutic drug monitoring and pharmacogenomics as means to improve the outcome, prevent/reduce antifungal toxicity and prevent the emergence of antifungal resistance. Finally, we present the new antifungals and their main characteristics.

/pdf/antifungals-from-pharmacokinetics-to-clinical-practice-3sh5kdjs.pdf

Antifungals: From Pharmacokinetics to Clinical Practice

Fungal pathogens cause significant human morbidity and mortality globally, where there is a propensity to infect vulnerable people such as the immunocompromised ones. There is increasing evidence of resistance to antifungal drugs, which has significant implications for cutaneous, invasive and bloodstream infections. The World Health Organization (WHO) published a priority list of fungal pathogens in October 2022, thus, highlighting that a crisis point has been reached where there is a pressing need to address the solutions. This review provides a timely insight into the challenges and implications on the topic of antifungal drug resistance along with discussing the effectiveness of established disease mitigation modalities and approaches. There is also a need to elucidate the cellular and molecular mechanisms of fungal resistance to inform effective solutions. The established fungal decontamination approaches are effective for medical device processing and sterilization, but the presence of pathogenic fungi in recalcitrant biofilms can lead to challenges, particularly during cleaning. Future design ideas for implantable and reusable medical devices should consider antifungal materials and appropriates for disinfection, and where it is relevant, sterilization. Preventing the growth of mycotoxin-producing fungi on foods through the use of appropriate end-to-end processes is advisable, as mycotoxins are recalcitrant and challenging to eliminate once they have formed.

/pdf/pathogenic-drug-resistant-fungi-a-review-of-mitigation-3vi5hy8i.pdf

Pathogenic Drug Resistant Fungi: A Review of Mitigation Strategies

Regenerative dentistry is a rapidly evolving field in dentistry, which has been driven by advancements in biomedical engineering research and the rising treatment expectations and demands that exceed the scope of conventional approaches. Tissue engineering, the foundation of regenerative dentistry, mainly focuses on 3 key components: stem cells, bioactive molecules, and scaffolds. Dental tissue-derived stem cells are especially significant in this regard due to their remarkable properties. Regenerative techniques have provided novel approaches to many conventional treatment strategies in various disciplines of dentistry. For instance, regenerative endodontic procedures such as pulp revascularisation have provided an alternative approach to conventional root canal treatment. In addition, conventional surgical and nonsurgical periodontal treatment is being taken over by modified approaches of guided tissue regeneration with the aid of 3-dimensional bioprinting and computer-aided design, which has revolutionised oral and maxillofacial tissue engineering. This review presents a concise overview of the latest treatment strategies that have emerged into clinical practice, potential future technologies, and the role of dental tissue-derived stem cells in regenerative dentistry. 

Advances in Regenerative Dentistry Approaches: An Update.

Itraconazole (ITZ) is a triazole antifungal agent characterized by broad-spectrum activity against fungal infections. The main drawback of ITZ, when applied topically, is the low skin permeability due to the stratum corneum, the outermost layer of the skin, which represents the main barrier for drug penetration. Therefore, this study aimed to prepare itraconazole as transferosomes (ITZ-TFS) to overcome the barrier function of the skin. ITZ-TFSs were prepared by thin lipid film hydration technique using different surfactants, sodium lauryl sulfate (SLS) and sodium deoxycholate (SDC). The prepared ITZ-TFS were evaluated for entrapment efficiency (EE) %, particle size, polydispersity index (PDI), zeta potential, and in vitro drug release to obtain an optimized formula. The surface morphology of the optimized formula of ITZ-TFS was determined by transmission electron microscope (TEM). The optimized formulation was prepared in the form of gel using hydroxyl propyl methyl cellulose (HPMC) gel base. The prepared ITZ-TFS gel was evaluated for homogeneity, drug content, spreadability, pH, and in vitro antifungal activity in comparison with the free ITZ gel. The prepared ITZ-TFS formulations exhibited high EE% ranging from 89.02 ± 1.65% to 98.17 ± 1.28% with particle size ranging from 132.6 ± 2.15 nm to 384.1 ± 3.46. The PDI for all ITZ-TFSs was less than 0.5 and had a negative zeta potential. The TEM image for the optimized formulation (ITZ-TFS4) showed spherical vesicles with a smooth surface. The prepared gels had good spreadability, pH, and acceptable drug content. ITZ-TFS gel showed higher antifungal activity than free ITZ gel as determined by zone of inhibition. ITZ was successfully prepared in form of TFSs with higher antifungal activity than the free drug.

/pdf/preparation-and-optimization-of-itraconazole-transferosomes-1s79pjml.pdf

Preparation and Optimization of Itraconazole Transferosomes-Loaded HPMC Hydrogel for Enhancing Its Antifungal Activity: 2^3 Full Factorial Design

Abstract The human blood–brain barrier (BBB) is a unique multicellular structure that is in critical demand for fundamental neuroscience studies and therapeutic evaluation. Despite substantial achievements in creating in vitro human BBB platforms, challenges in generating specifics of physiopathological relevance are viewed as impediments to the establishment of in vitro models. In this review, we provide insight into the development and deployment of in vitro BBB models that allow investigation of the physiology and pathology of neurological therapeutic avenues. First, we highlight the critical components, including cell sources, biomaterial glue collections, and engineering techniques to reconstruct a miniaturized human BBB. Second, we describe recent breakthroughs in human mini-BBBs for investigating biological mechanisms in neurology. Finally, we discuss the application of human mini-BBBs to medical approaches. This review provides strategies for understanding neurological diseases, a validation model for drug discovery, and a potential approach for generating personalized medicine. 

/pdf/human-mini-blood-brain-barrier-models-for-biomedical-3ivn9s6h.pdf

Human mini-blood–brain barrier models for biomedical neuroscience research: a review

Antifungal drugs prevent topical or invasive fungal infections (mycoses) either by stopping growth of fungi (termed fungistatic) or by killing the fungal cells (termed fungicidal). Antibiotics also prevent bacterial infections through either bacteriostatic or bactericidal mechanisms. These microorganisms successfully develop resistance against conventional drugs that are designed to kill or stop them from multiplying. When a fungus no longer responds to antifungal drug treatments and continues to grow, this is known as antifungal drug resistance. Bacteria have an amazing capacity to become resistant to antibiotic action as well, and the effectiveness of the scarce antifungal arsenal is jeopardised by this antibiotic resistance, which poses a severe threat to public health.

/pdf/antifungals-and-drug-resistance-2wmcgdyr.pdf

Antifungals and Drug Resistance

3D bioprinting is a rapidly evolving technique that has been found to have extensive applications in disease research, tissue engineering, and regenerative medicine. 3D bioprinting might be a solution to global organ shortages and the growing aversion to testing cell patterning for novel tissue fabrication and building superior disease models. It has the unrivaled capability of layer-by-layer deposition using different types of biomaterials, stem cells, and biomolecules with a perfectly regulated spatial distribution. The tissue regeneration of hollow organs has always been a challenge for medical science because of the complexities of their cell structures. In this mini review, we will address the status of the science behind tissue engineering and 3D bioprinting of epithelialized tubular hollow organs. This review will also cover the current challenges and prospects, as well as the application of these complicated 3D-printed organs.

/pdf/3d-bioprinting-of-human-hollow-organs-2ljmr0yo.pdf

3D Bioprinting of Human Hollow Organs

Abstract Background Artificial intelligence (AI) revolutionized the formulation and development of modern pharmaceuticals. With the help of AI, researchers can now optimize drug design, develop formulations, and streamline clinical trials in a much accurate and efficient way. Drug development might be greatly expedited and time-consuming procedure; however, with the help of AI this are significantly reduced. Main body of abstract The main advantages of AI in pharmaceutical formulation are its capacity to analyse vast amounts of data and spot patterns and connections that human researchers would miss. Various tools and technologies, such as ANN, fuzzy logic, neuro-fuzzy logic, and genetic algorithm are used for analysing the date, of which ANN is popular and mostly used. AI enables the discovery of novel pharmacological targets and the creation of more potent medications. AI may also be used to improve medication formulations by forecasting the solubility, stability, and bioavailability of drug candidates, increasing the likelihood that clinical trials will be successful. AI is also applied in designing clinical trials, reducing the time and cost of the process by identifying patient populations that are most likely to benefit from the treatment. Additionally, AI can monitor patients during clinical trials, detecting real-time adverse effects and adjusting dosages to improve patient outcomes. Conclusion AI is a potent pharmaceutical formulation and development tool, allowing researchers to analyse vast amounts of data, optimize drug formulations, and streamline clinical trials. As technology develops, experts anticipate that AI will increasingly show a crucial part in drug development, enabling faster, more efficient, and more effective treatments for various diseases. 

pdf/influence-of-artificial-intelligence-in-modern-32jdblrh7i.pdf

Influence of artificial intelligence in modern pharmaceutical formulation and drug development

/pdf/smart-nanobots-the-future-of-hiv-aids-treatment-1cy0h98og6.pdf

Smart-Nanobots: The Future of HIV AIDS Treatment

Our primary goal of this work was to create and test a mucoadhesive lyophilized rapid dissolving sublingual wafer of Alprazolam using a natural mucoadhesive agent extracted from black gram (Vigna mungo L.) seeds. We examined the pH, swelling volume, moisture absorption capability, mucoadhesive strength, and viscosity of the natural mucoadhesive agent. We compared it with synthetic mucoadhesive agents such as Hydroxypropyl cellulose (HPC) and Carbopol 934 (CP 934). The prepared wafers of both categories were characterized and compared for mechanical and texture properties, wetting time, disintegration time, Scanning Electron Microscopy (SEM), in vitro drug release, and ex vivo permeation study. We found that the pH of V. mungo mucilage (VMM) was 6.95±0.75, which lies between the normal sublingual mucosal range (pH 6-7), suggesting non-irritability to the mucosa. Attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) peak showed no significant interaction between Alprazolam and mucoadhesive materials. The micrographs of SEM predicted good porosity of the wafer which leads to rapid wetting, disintegration, and dissolution. It is inferred from the study that the fast-dissolving wafer prepared from the VMM gave a better result than the HPC wafer in respect of various parameters. Hence, this study discovered an alternative method to deliver Alprazolam. Keywords: Lyophilization, Permeability, Solid dosage form(s), Mucoadhesive, Texture

/pdf/fabrication-of-sublingual-alprazolam-wafers-using-3tlm1qo5.pdf

Fabrication of Sublingual Alprazolam Wafers using Mucoadhesive Vigna mungo L. Seeds and Characterized with Texture Analyzer QTS-25

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