Advanced drug delivery reviews最新文献

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.

A robust adaptive immune response is essential for combatting pathogens. In the wrong context such as due to genetic and environmental factors, however, the same mechanisms crucial for self-preservation can lead to a loss of self-tolerance. Resulting autoimmunity manifests in the development of a host of organ-specific or systemic autoimmune diseases, hallmarked by aberrant immune responses and tissue damage. The prevalence of autoimmune diseases is on the rise, medical management of which focuses primarily on pharmacological immunosuppression that places patients at a risk of side effects, including opportunistic infections and tumorigenesis. Biomaterial-based drug delivery systems confer many opportunities to address challenges associated with conventional disease management. Hydrogels, in particular, can protect encapsulated cargo (drug or cell therapeutics) from the host environment, afford their presentation in a controlled manner, and can be tailored to respond to disease conditions or support treatment via multiplexed functionality. Moreover, localized delivery to affected sites by these approaches has the potential to concentrate drug action at the site, reduce off-target exposure, and enhance patient compliance by reducing the need for frequent administration. Despite their many benefits for the management of autoimmune disease, such biomaterial-based approaches focus largely on the downstream effects of hypersensitivity mechanisms and have a limited capacity to eradicate the disease. In contrast, direct targeting of mechanisms of hypersensitivity reactions uniquely enables prophylaxis or the arrest of disease progression by mitigating the basis of autoimmunity. One promising approach is to induce self-antigen-specific tolerance, which specifically subdues damaging autoreactivity while otherwise retaining the normal immune responses. In this review, we will discuss hydrogel-based systems for the treatment of autoimmune disease, with a focus on those that target hypersensitivity mechanisms head-on. As the field continues to advance, it will expand the range of therapeutic choices for people coping with autoimmune diseases, providing fresh prospects for better clinical outcomes and improved quality of life.

To maximize therapeutic effects and minimize unwanted effects, the interest in drug targeting to the endoplasmic reticulum (ER) or Golgi apparatus (GA) has been recently growing because two organelles are distributing hubs of cellular building/signaling components (e.g., proteins, lipids, Ca²⁺) to other organelles and the plasma membrane. Their structural or functional damages induce organelle stress (i.e., ER or GA stress), and their aggravation is strongly related to diseases (e.g., cancers, liver diseases, brain diseases). Many efforts have been developed to image (patho)physiological functions (e.g., oxidative stress, protein/lipid-related processing) and characteristics (e.g., pH, temperature, biothiols, reactive oxygen species) in the target organelles and to deliver drugs for organelle disruption using organelle-targeting moieties. Therefore, this review will overview the structure, (patho)physiological functions/characteristics, and related diseases of the organelles of interest. Future direction on ER or GA targeting will be discussed by understanding current strategies and investigations on targeting, imaging/sensing, and therapeutic systems.

The intracellular journey of extracellular vesicles (EVs) cannot be ignored in various biological pathological processes. In this review, the biogenesis, biological functions, uptake pathways, intracellular trafficking routes, and biomedical applications of EVs were highlighted. Endosomal escape is a unique mode of EVs release. When vesicles escape from endosomes, they avoid the fate of fusing with lysosomes and being degraded, thus having the opportunity to directly enter the cytoplasm or other organelles. This escape mechanism is crucial for EVs to deliver specific signals or substances. The intracellular trafficking of EVs after endosomal escape is a complex and significant biological process that involves the coordinated work of various cellular structures and molecules. Through the in-depth study of this process, the function and regulatory mechanism of EVs are fully understood, providing new dimensions for future biomedical diagnosis and treatment.