Advanced drug delivery reviews最新文献

Transdermal administration remains an active research and development area as an alternative route for long-acting drug delivery. It avoids major drawbacks of conventional oral (gastrointestinal side effects, low drug bioavailability, and need for multiple dosing) or parenteral routes (invasiveness, pain, and psychological stress and bio-hazardous waste generated from needles), thereby increasing patient appeal and compliance. This review focuses on the current state of long-acting transdermal drug delivery, including adhesive patches, microneedles, and molecularly imprinted polymeric systems. Each subsection describes an approach including key considerations in formulation development, design, and process parameters with schematics. An overview of commercially available conventional (adhesive) patches for long-acting drug delivery (longer than 24 h), the reservoir- and matrix-type systems under preclinical evaluation, as well as the advanced transdermal formulations, such as the core-shell, nanoformulations-incorporated and stimuli-responsive microneedles, and 3D-printed and molecularly imprinted polymers that are in development, is also provided. Finally, we elaborated on translational aspects, challenges in patch formulation development, and future directions for the clinical advancement of new long-acting transdermal products.

Posterior eye disorders, such as age-related macular degeneration, diabetic retinopathy, and glaucoma, have a significant impact on human quality of life and are the primary cause of age-related retinal diseases among adults. There is a pressing need for innovative topical approaches to treat posterior eye disorders, as current methods often rely on invasive procedures with inherent risks. Limited success was attained in the realm of topical ophthalmic delivery through non-invasive means. Additionally, there exists a dearth of literature that delves into the potential of this approach for drug delivery and theranostic purposes, or that offers comprehensive design strategies for nanocarrier developers to surmount the significant physiological ocular barriers.

This review offers a thorough and up-to-date state-of-the-art overview of 40 studies on therapeutic loaded nanocarriers and theranostic devices that, to the best of our knowledge, represent all successful works that reached posterior eye segments through a topical non-invasive administration. Most importantly, based on the successful literature studies, this review provides a comprehensive summary of the potential design strategies that can be implemented during nanocarrier development to overcome each ocular barrier.

Subcutaneous (SC) drug delivery can be a safe, effective alternative to the traditional intravenous route of administration, potentially offering notable advantages for both patients and healthcare providers. The SC Drug Development & Delivery Consortium convened in 2018 to raise awareness of industry challenges to advance the development of patient-centric SC drug delivery strategies. The SC Consortium identified better understanding of patient preferences and perspectives as necessary to optimize SC product design attributes and help guide design decisions during SC product development. This manuscript provides a comprehensive overview of patient-centric factors for consideration in the SC drug delivery design and development process with the aim of establishing a foundation of existing knowledge for patient experiences related to SC drug delivery. This overview is informed by the outcomes of a multi-step survey of Consortium members and key pharmaceutical stakeholders. Framed in the context of the patient’s treatment journey, the survey findings offer future perspectives to fill data gaps to advance patient-centric SC drug delivery.

Immunotherapies have been transformative in many areas, including cancer treatments, allergies, and autoimmune diseases. However, significant challenges persist in extending the reach of these technologies to new indications and patients. Some of the major hurdles include narrow applicability to patient groups, transient efficacy, high cost burdens, poor immunogenicity, and side effects or off-target toxicity that results from lack of disease-specificity and inefficient delivery. Thus, there is a significant need for strategies that control immune responses generated by immunotherapies while targeting infection, cancer, allergy, and autoimmunity. Being the outermost barrier of the body and the first line of host defense, the skin presents a unique immunological interface to achieve these goals. The skin contains a high concentration of specialized immune cells, such as antigen-presenting cells and tissue-resident memory T cells. These cells feature diverse and potent combinations of immune receptors, providing access to cellular and molecular level control to modulate immune responses. Thus, skin provides accessible tissue, cellular, and molecular level controls that can be harnessed to improve immunotherapies. Biomaterial platforms – microneedles, nano- and micro-particles, scaffolds, and other technologies – are uniquely capable of modulating the specialized immunological niche in skin by targeting these distinct biological levels of control. This review highlights recent pre-clinical and clinical advances in biomaterial-based approaches to target and modulate immune signaling in the skin at the tissue, cellular, and molecular levels for immunotherapeutic applications. We begin by discussing skin cytoarchitecture and resident immune cells to establish the biological rationale for skin-targeting immunotherapies. This is followed by a critical presentation of biomaterial-based pre-clinical and clinical studies aimed at controlling the immune response in the skin for immunotherapy and therapeutic vaccine applications in cancer, allergy, and autoimmunity.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by an inflammatory microenvironment and cartilage erosion within the joint cavity. Currently, antirheumatic agents yield significant outcomes in RA treatment. However, their systemic administration is limited by inadequate drug retention in lesion areas and non-specific tissue distribution, reducing efficacy and increasing risks such as infection due to systemic immunosuppression. Development in local drug delivery technologies, such as nanostructure-based and scaffold-assisted delivery platforms, facilitate enhanced drug accumulation at the target site, controlled drug release, extended duration of the drug action, reduced both dosage and administration frequency, and ultimately improve therapeutic outcomes with minimized damage to healthy tissues. In this review, we introduced pathogenesis and clinically used therapeutic agents for RA, comprehensively summarized locally administered nanostructure-based and scaffold-assisted drug delivery systems, aiming at improving the therapeutic efficiency of RA by alleviating the inflammatory response, preventing bone erosion and promoting cartilage regeneration. In addition, the challenges and future prospects of local delivery for clinical translation in RA are discussed.

Neutrophils play an essential role as ‘first responders’ in the immune response, necessitating many immune-modulating capabilities. Chronic, unresolved inflammation is heavily implicated in the progression and tissue-degrading effects of autoimmune disease. Neutrophils modulate disease pathogenesis by interacting with the inflammatory and autoreactive cells through effector functions, including signaling, degranulation, and neutrophil extracellular traps (NETs) release. Since the current gold standard systemic glucocorticoid administration has many drawbacks and side effects, targeting neutrophils in autoimmunity provides a new approach to developing therapeutics. Nanoparticles enable targeting of specific cell types and controlled release of a loaded drug cargo. Thus, leveraging nanoparticle properties and interactions with neutrophils provides an exciting new direction toward novel therapies for autoimmune diseases. Additionally, recent work has utilized neutrophil properties to design novel targeted particles for delivery into previously inaccessible areas. Here, we outline nanoparticle-based strategies to modulate neutrophil activity in autoimmunity, including various nanoparticle formulations and neutrophil-derived targeting.

With the aging population on the rise, neurodegenerative disorders have taken center stage as a significant health concern. The blood–brain barrier (BBB) plays an important role to maintain the stability of central nervous system, yet it poses a formidable obstacle to delivering drugs for neurodegenerative disease therapy. Various methods have been devised to confront this challenge, each carrying its own set of limitations. One particularly promising noninvasive approach involves the utilization of focused ultrasound (FUS) combined with contrast agents—microbubbles (MBs) to achieve transient and reversible BBB opening. This review provides a comprehensive exploration of the fundamental mechanisms behind FUS/MBs-mediated BBB opening and spotlights recent breakthroughs in its application for neurodegenerative diseases. Furthermore, it addresses the current challenges and presents future perspectives in this field.

The etiology of cancers is multifactorial, with certain bacteria established as contributors to carcinogenesis. As the understanding of carcinogenic bacteria deepens, interest in cancer treatment through bacterial eradication is growing. Among emerging antibacterial platforms, cell membrane-coated nanoparticles (CNPs), constructed by enveloping synthetic substrates with natural cell membranes, exhibit significant promise in overcoming challenges encountered by traditional antibiotics. This article reviews recent advancements in developing CNPs for targeting carcinogenic bacteria. It first summarizes the mechanisms of carcinogenic bacteria and the status of cancer treatment through bacterial eradication. Then, it reviews engineering strategies for developing highly functional and multitasking CNPs and examines the emerging applications of CNPs in combating carcinogenic bacteria. These applications include neutralizing virulence factors to enhance bacterial eradication, exploiting bacterium-host binding for precise antibiotic delivery, and modulating antibacterial immunity to inhibit bacterial growth. Overall, this article aims to inspire technological innovations in developing CNPs for effective cancer treatment through oncogenic bacterial targeting.