搜索结果：Advanced drug delivery reviews

Advances in artificial intelligence (AI) and synthetic biology are transforming biological research and biotechnology. These fields are for the first time enabling the design and development of human and bacterial cells that can serve as "living" drug delivery vehicles that perform sustained release of therapeutic cargo with spatiotemporal control. In recent years, human and bacterial cells have been engineered to deliver peptides, proteins, and biologics for treating a wide range of human diseases using synthetic biology approaches. To engineer effective living drug delivery systems, detailed knowledge is required about how to design receptors that can specifically sense the tissues targeted for drug delivery, signaling networks that can process signals from these receptors, and gene circuits that can control therapeutic cargo production and release. However, elucidating such receptors, signal processing and gene regulatory elements, and gene circuit compositions by traditional design-build-test-learn approaches is difficult and low throughput. Here we review how advances in AI and synthetic biology are meeting these challenges. We describe examples of how human cells and bacteria are engineered to become living drug delivery vehicles. We discuss how AI and synthetic biology approaches are being applied to discover the sequence-to-function design principles for engineering synthetic receptors, signaling proteins, and gene regulatory elements and the composition-to-function design principles for engineering synthetic gene circuits. We share an outlook on opportunities for AI and synthetic biology to synergize for creating next-generation living drug delivery systems.

Microneedles have achieved remarkable breakthroughs in the fields of transdermal drug delivery and minimally invasive diagnosis and treatment. Over the past decades, it has been remarkably improved by developing delivery and diagnostic strategies based on the microneedle (MN) platform and leveraging its characteristic of minimally invasive penetration through the stratum corneum barrier, the bioavailability of drugs and the accuracy of diagnosis and treatment, achieving efficient local therapy while reducing the systemic side effects of drugs. This article first explains and clarifies the paradigm shift in the evolution of microneedle technology from passive delivery tools to active intelligent systems. Subsequently, it systematically reviews the latest advances in the 4D collaborative design of material composition, geometric structure, payload, and functional intelligence for constructing advanced microneedle systems, including tunable bionic/composite matrices, complex structures enabling spatiotemporally programed drug release, loading of multiscale therapeutic agents, and intelligent functions integrating sensing, response, and feedback control. At the end of the paper, the core implementation obstacles and emerging opportunities faced by this technology in clinical translation and personalized medicine are prospectively discussed.

Inorganic nanoparticles (NPs) have played a central role in the development of nanomedicine, offering unique physicochemical properties that enable imaging, therapy, and multifunctional drug delivery. Despite extensive progress, the clinical translation of nanomedicines remains limited, largely due to challenges associated with reproducibility, scalability, toxicity, and, critically, inefficient delivery to target tissues. In this context, microfluidic technologies have emerged as a powerful platform to address many of these limitations by enabling continuous, highly controlled, and reproducible NP synthesis under well-defined flow conditions. This review provides a comprehensive overview of recent advances in the continuous-flow microfluidic synthesis of inorganic NPs for drug delivery applications. Key microfluidic parameters governing NP formation are discussed, including mixing regimes, residence time, flow configuration, and scale-up, and analyze how these factors influence size, dispersity, composition, and functional performance. Particular attention is devoted to plasmonic NPs, non-metallic magnetic NPs, and other relevant inorganic systems such as quantum dots and silica NPs, highlighting both achievements and remaining challenges in their microfluidic production. Beyond purely inorganic NPs, the review examines the growing field of hybrid organic-inorganic NPs, where inorganic cores are integrated with polymers, lipids, or biomimetic components to combine synthetic functionality with biological performance. These hybrid architectures represent a promising strategy to overcome key barriers in drug delivery, including immune clearance, poor targeting efficiency, and limited therapeutic index, while posing additional synthetic and integration challenges that microfluidics is uniquely positioned to address. Finally, current bottlenecks and future perspectives for microfluidic nanomanufacturing are discussed, including productivity, multistep process integration, in-line purification, and automation. Microfluidic platforms, especially when combined with hybrid and bioinspired NP design, are positioned as enabling technologies to bridge the gap between advanced NP engineering and clinically translatable nanomedicines.

Drug delivery research strongly depends on experimental models that faithfully mimic the tumor microenvironment (TME) and its barriers to evaluate therapeutic efficacy. Conventional systems provide valuable insights but suffer from some limitations in physiological relevance, reproducibility, scalability or translational predictability. In this context, microfluidic 'tumor-on-chip' platforms have emerged as innovative tools that integrate engineering technology to model biological complexity, offering controlled microenvironments to investigate drug penetration, transport dynamics, and therapeutic response. A distinctive aspect of these microsystems is the possibility of incorporating matrices that mimic the extracellular matrix (ECM) of different tissues. These matrices enhance the ability of the in vitro models to replicate the structural, biochemical, and mechanical features of solid tumors. In this review, we focus on the application of microfluidic matrix-integrated tumor-on-chip platforms for drug delivery evaluation. We first outline key microenvironmental features that regulate therapeutic efficacy and discuss how they can be engineered within microfluidic models. We then examine how transport dynamics and delivery mechanisms are modeled under physiologically relevant conditions and review the use of these platforms to assess a broad range of therapeutic strategies, including nanocarriers, biologics, and gene- and cell-based therapies. Finally, we highlight emerging computational and data-driven approaches, together with current translational and regulatory perspectives, that position matrix-integrated tumor-on-chip technologies as powerful preclinical tools. These models aim to bridge the gap between simplified in vitro assays and more complex in vivo studies, ultimately accelerating the translation of drug delivery systems into clinical practice and paving the way for more personalized therapeutic strategies.

Biologics is emerging as fastest growing field of drug development offering specificity and high therapeutic potential. However, their therapeutic efficacy is dependent on their route of administration and targeted delivery. Unlike small molecules, biologics face stability, permeability, solubility and immunogenicity challenges due to their inherent features. Hence tailored approaches are required in formulation development to assure their time-and site-specific action. In this review, we summarized the general and route-specific barriers that this group of drugs encounter once in contact with administration site. We listed the most common approaches to overcome the barriers and presented examples of different delivery systems that were proposed to deal with route-specific challenges. We also addressed the role devices play in assisted drug delivery and their choices related to expected use. We highlighted device-biologic combinations and discussed our perspectives on improving development using machine learning.

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Nanodrug delivery systems (NDDSs) offer distinctive advantages in tumor immunotherapy, not only by enhancing drug distribution, targeting, and bioavailability but also by actively engaging in immune regulation through multiple mechanisms. In recent years, researchers have increasingly recognized that the NDDS itself can act as a pivotal driver in immune activation, participating in the induction of immunogenic cell death (ICD), the activation of dendritic cells (DCs) and T cells, the reprogramming of immunosuppressive cell populations, and the remodeling of the tumor immune microenvironment (TIME). Various nanomaterial platforms are undergoing a functional transition from "drug carriers" to "immune amplifiers." These systems are capable of spatiotemporally orchestrating synergistic responses between innate and adaptive immunity or directly modulating immune cells through specific signaling pathways to establish durable immune memory. This review systematically summarizes the key design principles and immune-activating mechanisms of diverse nanocarriers, and discusses their prospective applications in immunotherapy, particularly in combination with other therapeutic modalities. Emerging approaches, including AI-driven strategies, as well as current challenges are also highlighted. The work aims to provide theoretical foundations and design insights for the development of intelligent, immune-driven NDDSs that can advance the next generation of precision cancer immunotherapy.

The gastrointestinal tract is a dynamic ecosystem where biophysical forces, enzymatic gradients, and microbial metabolism converge to govern the fate of orally administered therapeutics. These multifactorial interactions-spanning shear stress, mucus transport, and microbial metabolism-collectively shape absorption, transformation, and therapeutic response. Such complexity drives the wide interindividual variability in oral pharmacokinetics and pharmacodynamics, challenging predictive modeling and formulation design. Capturing these intertwined processes requires experimental systems that bridge the physiological fidelity of human tissue with the analytical control of engineered models. Microphysiological Gut-on-a-Chip (GoC) platforms have emerged as promising tools that reconstruct human intestinal architecture and function with high precision. These devices integrate living epithelia, peristaltic motion, oxygen and nutrient gradients, immune and microbial co-cultures, and on-chip sensing within precisely engineered microenvironments. They enable direct observation and quantification of luminal-mesenchymal communication, barrier regulation, and metabolite exchange under physiologically relevant flow. This review delineates how GoC technology is advancing oral drug delivery by bridging biology, microengineering, and pharmacology. We summarize advances across three therapeutic domains-small-molecule drugs, macromolecular and biopharmaceutical agents, and microbiome-interacting therapeutics-highlighting how GoCs now recapitulate absorption, enzymatic metabolism, immune modulation, and microbial transformation in human-relevant contexts. By merging organ-level physiology with analytical precision, GoCs establish a unified platform for predicting oral bioavailability and systemic exposure. As these systems evolve toward sensor-integrated, multi-omics, and AI-enabled designs, they are poised to become the mechanistic backbone of next-generation preclinical drug discovery and personalized oral therapeutics.

Artificial intelligence (AI) is reshaping pharmaceutical research by enabling data-intensive tasks to be performed with unprecedented speed and accuracy. While oral delivery remains the most common route of administration, it is dominated by a "one-size-fits-all" paradigm that fails to accommodate inter-individual variability, often leading to suboptimal efficacy or adverse reactions. AI offers a path toward personalised delivery by integrating patient-specific data to predict dose requirements and guide the development of bespoke dosage forms. When coupled with three-dimensional printing (3DP), AI-driven workflows enable decentralised, on-demand production of personalised medicines. This review examines advances of machine learning (ML) in enabling dose prediction, formulation optimisation, and digital manufacturing. It highlights emerging opportunities alongside challenges in data quality, regulatory acceptance, and clinical implementation. We discuss the need for collaboration between academia, industry, and regulators to establish interoperable datasets and robust quality-by-design frameworks. Together, these developments point toward a future in which oral drug delivery is increasingly precise, adaptive, and patient-centred.

Peptide-based therapeutics are widely employed in the treatment and management of various medical conditions, including diabetes, obesity, cancer, rare diseases, and microbial infections. This chapter reviews the evolution of technologies used in peptide production including chemical synthesis, recombinant DNA technology, and other advanced methods that have driven significant progress in pharmaceutical development. However, the development of peptide therapeutics is challenged by issues related to high production costs, limited stability, delivery barriers, and potential toxicity. To overcome these issues, recombinant live biotherapeutics (rLBPs), can be utilized as live microbioreactor, where genetically engineered microorganisms are employed to produce and deliver therapeutic peptides directly within the host. Recombinant LBPs enable accurate, sustained, and targeted delivery of therapeutic peptides with enhanced safety, efficacy and cost-effective manufacturing. Furthermore, this chapter highlights the advancements of genetic engineering tools that have enabled the modification and development of rLBPs as microbioreactor, highlighting their emerging role and therapeutic potential in curing disorders.

Controlling plant diseases caused by phytopathogenic fungi requires innovative approaches that are environmentally friendly and sustainable. One promising strategy is the use of RNA interference (RNAi)-based biopesticides. This technology offers the advantage of high specificity to target pathogens without harming beneficial non-target microorganisms, and leaves no harmful residues in the environment. RNAi offers theoretical advantages in reducing single-gene resistance selection by targeting multiple genes. In addition, resistance must be considered in the development and application of RNAi biopesticides because organisms can still develop resistance. The effectiveness of RNAi is greatly influenced by the pathogen's ability to absorb dsRNA molecules, which varies between fungal species. In this article, researchers review the latest developments in the application of RNAi to control phytopathogenic fungi, focusing on the mechanism of action of RNAi, biological barriers that affect its efficiency, and various RNAi delivery strategies, including transgenic and non-transgenic approaches such as spray induced gene silencing (SIGS). Unlike previous reviews that tended to discuss general RNAi applications or only one delivery method, this article provides a comprehensive analysis of the challenges and opportunities in developing effective and specific RNAi biopesticides against plant pathogenic fungi.

Intracellular delivery of therapeutic biomolecules represents a fundamental prerequisite for cell-based therapies and precision medicine, yet existing delivery methods present critical limitations. Viral vectors, while effective, pose safety risks including immunogenicity and insertional mutagenesis. Bulk electroporation offers a non-viral alternative but suffers from high cytotoxicity, heterogeneous electric field distributions, and poor efficiency in primary cells due to excessive voltage requirements and uncontrolled Joule heating. Microfluidic electroporation exploits microscale physics to decouple transfection efficiency from cell viability. By reducing electrode spacing to micrometers, these platforms achieve necessary field strengths at voltages below 50 V, minimizing Joule heating and electrolysis byproducts that plague bulk methods. Static platforms, including nanostructure-assisted designs, provide subcellular precision through localized field enhancement and real-time impedance monitoring, enabling mechanistic investigation of pore formation dynamics. Continuous-flow systems transform electroporation into a scalable manufacturing process, achieving throughputs of 108-109 cells per minute required for clinical cell therapy production while maintaining viabilities above 90% through hydrodynamic focusing and optimized channel geometries. Despite these engineering advances, systematic benchmarking against Current Good Manufacturing Practice (cGMP)-compliant commercial electroporators reveals critical translational barriers: reliance on research-grade polydimethylsiloxane instead of medical-grade thermoplastics, open manual workflows incompatible with sterile closed-system requirements, lack of validated process control protocols, and insufficient biological verification beyond transient fluorescent protein expression. Furthermore, cargo-specific constraints, including nuclear transport requirements for plasmid DNA versus ribonucleoprotein complexes and distinctions between transient mRNA expression versus permanent CRISPR/Cas9 genomic integration, demand fundamentally different optimization strategies rarely addressed in device-focused studies. Establishing microfluidic electroporation as a viable clinical platform requires integrated manufacturing modules coupling electroporation with upstream buffer exchange and downstream cell sorting, along with implementation of real-time process analytical technology and closed-loop artificial intelligence-driven control. Early regulatory engagement to establish Drug Master File pathways will enable broad therapeutic applications.

Regenerative medicine increasingly relies on therapeutic cells such as mesenchymal stem cells and induced pluripotent stem cells, and engineered cellular constructs to repair and restore damaged tissues. However, clinical translation is constrained by challenges in maintaining viability, ensuring precise localization, achieving durable engraftment of transplanted cells, and producing sufficient numbers of clinically relevant cells. Microfluidic technologies are emerging as transformative tools to address these barriers by enabling precise manipulation of fluids, biomaterials, and cells at the microscale. In the context of therapeutic cell delivery, these platforms can improve early retention and engraftment compared with conventional injections, provide tighter control over delivered cell dose, preserve viability under defined shear conditions, enable site-specific placement of cell-laden carriers, and support immunoisolating or immunomodulatory architectures that enhance immune safety. These platforms provide controlled microenvironments that mimic native tissue architecture, regulate biochemical and mechanical cues, and support the scalable production of cell-laden carriers. Advances in microfabrication techniques, ranging from soft lithography and thermoplastics to 3D printing and hydrogel integration, have expanded device versatility, while embedded sensors enable real-time monitoring of cell state, metabolism, and differentiation. Beyond single-cell delivery, microfluidics facilitates the encapsulation, co-culture, and organoid assembly of cells, enabling multicellular systems with physiologically relevant interactions. Coupled with CRISPR-based genome editing and synthetic biology, these platforms allow the engineering of "smart" therapeutic cells with enhanced regenerative and immunomodulatory functions. Applications extend to microfluidic sorting for stem cell purification, controlled differentiation, and advanced manufacturing of immune cell therapies such as chimeric antigen receptor (CAR)T cells, alongside exosome-based strategies for precision delivery. Despite promising progress, challenges remain in regulatory standardization, large-scale manufacturing, and integration with clinical workflows. This review highlights state-of-the-art microfluidic approaches for controlled delivery of stem cells and engineered cells, emphasizing how these systems impact key delivery metrics such as retention, dose control, shear resilience, spatial targeting, and immune interfaces to advance precision regenerative medicine.

The drug development for central nervous system (CNS) disorders, particularly neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, faces formidable challenges. While proteolysis-targeting chimeras (PROTACs) represent a paradigm-shifting modality by redefining target engagement mechanisms, their clinical translation remains hindered by limited blood-brain barrier (BBB) permeability and suboptimal pharmacokinetic profiles. In recent years, a range of CNS-targeted delivery strategies have emerged, advancing PROTAC research toward more translatable therapeutic applications. This review highlights recent advances and persistent challenges in noninvasive BBB-penetrant delivery systems, including viral vectors, engineered exosomes, functionalized nanocarriers, and cell membrane-derived biomimetic vehicles, with a particular emphasis on intranasal administration as a direct route to the brain. Parallel progress in rational molecular engineering, encompassing E3 ligase selection, linker polarity and rigidity modulation, and optimization of target-binding ligands, has further enhanced PROTAC drug-likeness and BBB transport efficiency. Current CNS-directed PROTAC designs increasingly incorporate cell-penetrating peptides, nanoparticles, and prodrug formulations to balance stability, selectivity, and brain exposure. Future advanced PROTAC delivery platforms require integrating multifunctional nanocarriers with rational structural optimization to enhance BBB permeability. Further artificial intelligence-accelerated molecular design and targeted protein degradation technologies offer novel avenues for addressing undruggable CNS targets.

As a chronic systemic autoimmune disease, rheumatoid arthritis (RA) is characterized by persistent synovial inflammation, progressive joint destruction, and substantial long-term disability. These arthritic symptoms are mainly driven by fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes (MLS) via secreting pro-inflammatory cytokines, matrix-degrading enzymes, and osteoclast-activating factors. Considerable systemic side effects and drug resistance constrain conventional pharmacotherapies. In recent years, various nanoplatforms have demonstrated significant potential in achieving precise drug delivery and multimodal therapeutic modulation in RA. However, few reviews have centered on MLS and FLS as the framework and elaborated on the corresponding treatment strategies of RA. This review first elucidates the key mechanistic roles of FLS and MLS in RA pathogenesis, then systematically categorizes the design principles of advanced nanoplatforms for targeting or regulating these synovial cell subsets. Moving beyond single-cell or single-pathway intervention, we highlight emerging nanotherapeutic strategies that achieve system-level modulation of the inflammatory synovial microenvironment. We further discuss the major challenges facing nanoplatform-based precision therapy and propose future directions. Ultimately, this review proposes a logical framework centered on FLS and MLS and integrates dual-cell regulation, adaptive microenvironment-response, and immune-metabolic reprogramming strategies, which can accelerate the widespread translation of advanced nanoplatforms and provide a systematic roadmap for more effective and precise management of RA.

Subcutaneous (SC) administration offers multiple advantages over intravenous (IV) administration across different therapeutic areas and chemical modalities. Despite progress, some knowledge gaps persist in understanding the SC injection process, drug fate within the SC site, and SC absorption and bioavailability. This review provides an overview of emerging modeling and simulation techniques to tackle these knowledge gaps. Various in silico mechanistic models have been used to simulate SC injection dynamics, injection depot geometry, tissue backpressure, tissue deformation, changes in tissue porosity and permeability, drug migration within the SC site, and drug absorption. On the other hand, in vitro models and methods have advanced to emulate in vivo SC tissue, assess critical quality attributes of SC drug products, and establish in vitro-in vivo correlations. Additionally, this review discussed predictive methods for mAb SC bioavailability. Advances in modeling and simulation techniques can accelerate the development of SC drug products.

Coacervation phenomena in the biological world can be categorized as intracellular and extracellular coacervation. Intracellular coacervation has inspired the formation of membrane-free coacervate droplets and the development of droplet-based drug delivery systems, whereas the extracellular coacervation observed in marine mussels has motivated the creation of numerous coacervate-derived hydrogels. Coacervate-derived hydrogels, formed via liquid-liquid phase separation and subsequent gelation, represent a promising class of biomaterials, particularly for advanced drug delivery. Given the current lack of systematic reviews on coacervate-derived hydrogels, this review systematically elucidated their formation mechanism, characterization techniques, material systems (including natural/synthetic polymers, peptides, and inorganic components), and diverse forms (e.g., injectable, powder-based, stimuli-responsive). We particularly highlighted their exceptional potential in drug delivery, leveraging their high loading capacity, gentle encapsulation that preserves bioactivity, and tunable release kinetics in response to physiological stimuli. Beyond drug delivery, we also discussed their broad applications in bioadhesives, tissue engineering, 3D printing, and artificial tissue construction. Furthermore, this review discussed the current challenges faced by coacervate-derived hydrogels, including in vivo stability, precise control over drug release, long-term biosafety, and clinical translation. It also provided perspectives on future research directions, aiming to promote the further development and application of these materials in precision medicine and regenerative medicine.

Psoriasis is a chronic, immune-mediated disorder with strong genetic susceptibility and environmental triggers, characterized by excessive proliferation of keratinocytes and recruitment of inflammatory cells. Affecting 2-3% of the global population and represents a significant public health challenge. In psoriasis, the skin barrier is altered rather than uniformly enhanced, and its permeability varies with drug types and disease states, which may affect the effective delivery of drugs to affected areas. Nanotechnology demonstrates potential in drug delivery, protecting drug molecules from degradation, enabling targeted therapy, and reducing side effects, thereby improving pharmacokinetics and enhancing the bioavailability of therapeutic agents. This review specifically examines the emergence of multimodal nanotherapeutic approaches, which defined as the strategic integration of two or more distinct therapeutic modalities (e.g., pharmacotherapy paired with phototherapy, gene editing, or RNA interference) within a unified nanocarrier platform to achieve synergistic efficacy. By systematically evaluating these advanced combinatory strategies, this review provides a distinct perspective compared to existing literature, which predominantly focuses on conventional, single-mode drug delivery systems. To this end, it reviews nanotechnology combined with multiple therapies and introduces the current advantages and disadvantages of integrating nanotechnology with conventional anti-psoriatic drugs Finally, it presents the challenges and prospects of using nanotechnology to treat psoriasis and provides reliable solutions for its clinical management. Overall, this review advances psoriasis treatment toward precision and efficiency, revealing the broad prospects of nanomedicine in conquering this intractable disease.

There is a growing demand for high-concentration protein formulations (HCPFs), driven by certain therapeutics that require high doses and the volume limitations of subcutaneous administration. However, downstream processing and fill-finish for these HCPFs plays a critical role and remains a major limitation. It accounts for nearly 60% of the total production cost and faces significant challenges in scalability and efficiency. These challenges are largely attributed to inherent complexity, which involve multiple unit operations such as ultrafiltration, bulk drug substance freezing, thawing, mixing, sterile filtration and drug product fill-finish. This review provides a comprehensive overview of downstream processing and fill-finish for high-concentration protein formulations, highlighting the key challenges, particularly related to drug stability, (such as protein aggregation, or particulate formation), viscosity and solubility (such as turbidity or phase separation). Addressing these multifactorial challenges demands various strategies that include formulation and process optimization, and the use of specialized delivery systems which are discussed herewith. Moreover, emerging trends such as process analytical technologies (PAT), use of non-aqueous delivery vehicles and potential of using solid suspensions are also highlighted as promising strategies for overcoming the current limitations. Finally, to address the real-world applications, case studies of two FDA-approved high-concentration formulations (up to 200 mg/mL) are presented illustrating the need for formulation and process design for enabling successful clinical translation.