Advanced drug delivery reviews最新文献

This review examines the role of model-informed drug development (MIDD) in advancing antibacterial and antiviral drug development, with an emphasis on the inclusion of host system dynamics into modeling efforts. Amidst the growing challenges of multidrug resistance and diminishing market returns, innovative methodologies are crucial for continuous drug discovery and development. The MIDD approach, with its robust capacity to integrate diverse data types, offers a promising solution. In particular, the utilization of appropriate modeling and simulation techniques for better characterization and early assessment of drug resistance are discussed. The evolution of MIDD practices across different infectious disease fields is also summarized, and compared to advancements achieved in oncology. Moving forward, the application of MIDD should expand into host system dynamics as these considerations are critical for the development of “live drugs” (e.g. chimeric antigen receptor T cells or bacteriophages) to address issues like antibiotic resistance or latent viral infections.

Deformability is one of the critical attributes of nanoparticle (NP) drug carriers, along with size, shape, and surface properties. It affects various aspects of NP biotransport, ranging from circulation and biodistribution to interactions with biological barriers and target cells. Recent studies report additional roles of NP deformability in biotransport processes, including protein corona formation, intracellular trafficking, and organelle distribution. This review focuses on the literature published in the past five years to update our understanding of NP deformability and its effect on NP biotransport. We introduce different methods of modulating and evaluating NP deformability and showcase recent studies that compare a series of NPs in their performance in biotransport events at all levels, highlighting the consensus and disagreement of the findings. It concludes with a perspective on the intricacy of systematic investigation of NP deformability and future opportunities to advance its control toward optimal drug delivery.

Drug delivery strategies for local immunomodulation hold tremendous promise compared to current clinical gold-standard systemic immunosuppression as they could improve the benefit to risk ratio of life-saving or life-enhancing transplants. Such strategies have facilitated prolonged graft survival in animal models at lower drug doses while minimizing off-target effects. Despite the promising outcomes in preclinical animal studies, progression of these strategies to clinical trials has faced challenges. A comprehensive understanding of the translational barriers is a critical first step towards clinical validation of effective immunomodulatory drug delivery protocols proven for safety and tolerability in pre-clinical animal models. This review overviews the current state-of-the-art in local immunomodulatory strategies for transplantation and outlines the key challenges hindering their clinical translation.

RNA medicines represent a paradigm shift in treatment and prevention of critical diseases of global significance, e.g., infectious diseases. The highly successful messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were developed at record speed during the coronavirus disease 2019 pandemic. A consequence of this is exceptionally shortened vaccine development times, which in combination with adaptability makes the RNA vaccine technology highly attractive against infectious diseases and for pandemic preparedness. Here, we review state of the art in the design and delivery of RNA vaccines for infectious diseases based on different RNA modalities, including linear mRNA, self-amplifying RNA, trans-amplifying RNA, and circular RNA. We provide an overview of the clinical pipeline of RNA vaccines for infectious diseases, and present analytical procedures, which are paramount for characterizing quality attributes and guaranteeing their quality, and we discuss future perspectives for using RNA vaccines to combat pathogens beyond SARS-CoV-2.

The evaluation of the diffusion properties of different molecules in tissues is a subject of great interest in various fields, such as dermatology/cosmetology, clinical medicine, implantology and food preservation. In this review, a discussion of recent studies that used kinetic spectroscopy measurements to evaluate such diffusion properties in various tissues is made. By immersing ex vivo tissues in agents or by topical application of those agents in vivo, their diffusion properties can be evaluated by kinetic collimated transmittance or diffuse reflectance spectroscopy. Using this method, recent studies were able to discriminate the diffusion properties of agents between healthy and diseased tissues, especially in the cases of cancer and diabetes mellitus. In the case of cancer, it was also possible to evaluate an increase of 5% in the mobile water content from the healthy to the cancerous colorectal and kidney tissues. Considering the application of some agents to living organisms or food products to protect them from deterioration during low temperature preservation (cryopreservation), and knowing that such agent inclusion may be reversed, some studies in these fields are also discussed. Considering the broadband application of the optical spectroscopy evaluation of the diffusion properties of agents in tissues and the physiological diagnostic data that such method can acquire, further studies concerning the optimization of fruit sweetness or evaluation of poison diffusion in tissues or antidote application for treatment optimization purposes are indicated as future perspectives.

Intrinsically disordered proteins (IDPs) exhibit molecular-level conformational dynamics that are functionally harnessed across a wide range of fascinating biological phenomena. The low sequence complexity of IDPs has led to the design and development of intrinsically-disordered protein polymers (IDPPs), a class of engineered repeat IDPs with stimuli-responsive properties. The perfect repetitive architecture of IDPPs allows for repeat-level encoding of tunable protein functionality. Designer IDPPs can be modeled on endogenous IDPs or engineered de novo as protein polymers with dual biophysical and biological functionality. Their properties can be rationally tailored to access enigmatic IDP biology and to create programmable smart biomaterials. With the goal of inspiring the bioengineering of multifunctional IDP-based materials, here we synthesize recent multidisciplinary progress in programming and exploiting the bio-functionality of IDPPs and IDPP-containing proteins. Collectively, expanding beyond the traditional sequence space of extracellular IDPs, emergent sequence-level control of IDPP functionality is fueling the bioengineering of self-assembling biomaterials, advanced drug delivery systems, tissue scaffolds, and biomolecular condensates —genetically encoded organelle-like structures. Looking forward, we emphasize open challenges and emerging opportunities, arguing that the intracellular behaviors of IDPPs represent a rich space for biomedical discovery and innovation. Combined with the intense focus on IDP biology, the growing landscape of IDPPs and their biomedical applications set the stage for the accelerated engineering of high-value biotechnologies and biomaterials.

Pharmacological research has expanded to the nanoscale level with advanced imaging technologies, enabling the analysis of drug distribution at the cellular organelle level. These advances in research techniques have contributed to the targeting of cellular organelles to address the fundamental causes of diseases. Beyond navigating the hurdles of reaching lesion tissues upon administration and identifying target cells within these tissues, controlling drug accumulation at the organelle level is the most refined method of disease management. This approach opens new avenues for the development of more potent therapeutic strategies by delving into the intricate roles and interplay of cellular organelles. Thus, organelle-targeted approaches help overcome the limitations of conventional therapies by precisely regulating functionally compartmentalized spaces based on their environment. This review discusses the basic concepts of organelle targeting research and proposes strategies to target diseases arising from organelle dysfunction. We also address the current challenges faced by organelle targeting and explore future research directions.