Aug 2026· Therapeutic delivery· Vol 17, pp.
1-25
· 0 citations· 114 references
Medicine
TL;DR
This review comprehensively examines major nanocarrier platforms, including lipid-based, polymeric, inorganic, and hybrid systems, with emphasis on their structural design and functional properties.
Abstract
INTRODUCTION
Nanoparticle-based drug delivery has emerged as a transformative approach in modern therapeutics, offering improved targeting efficiency, enhanced pharmacokinetics, and reduced systemic toxicity compared to conventional drug delivery systems.
AREAS COVERED
This review comprehensively examines major nanocarrier platforms, including lipid-based, polymeric, inorganic, and hybrid systems, with emphasis on their structural design and functional properties. It further explores current advancements in targeting strategies, including passive targeting via the enhanced permeability and retention (EPR) effect and active targeting through ligand-receptor interactions involving antibodies, peptides, aptamers, and small molecules. Key biological and technological barriers to clinical translation are also discussed, such as tumor heterogeneity, abnormal vasculature, dense extracellular matrix, immune clearance, and limited cellular uptake. Additionally, emerging stimuli-responsive systems, including pH-, redox-, and enzyme-sensitive nanocarriers, are highlighted for their role in controlled and site-specific drug release.
EXPERT OPINION/COMMENTARY
Despite significant progress, the clinical translation of nanomedicine remains constrained by biological complexities and scalability challenges. Future advancements integrating biomimetic strategies, multifunctional design, and artificial intelligence-driven modeling are expected to enhance targeting precision, biocompatibility, and translational success.
Nanomedicine has emerged as a transformative strategy for precision-controlled drug delivery. It addresses key limitations of conventional therapeutics such as poor tissue selectivity, rapid degradation, and systemic toxicity. By employing nanoscale carriers (including lipid-based systems, polymeric nanoparticles, inorganic nanostructures, biomimetic vesicles, and hybrid platforms), researchers have developed multifunctional delivery systems capable of enhancing pharmacokinetics, biodistribution, and therapeutic index. Beyond passive accumulation through the enhanced permeability and retention (EPR) effect, modern nanocarriers integrate active ligand-mediated targeting, stimuli-responsive release mechanisms, and multilevel strategies that enable spatial, temporal, and cellular precision. Recent preclinical
in vivo
studies across oncology, central nervous system, and vascular disease models demonstrate significantly improved target-site accumulation, sustained drug release, and reduced off-target toxicity compared with free drug formulations. Advances in organelle-specific targeting, combination therapies, and theranostic platforms further highlight the expanding versatility of nanomedicine. However, translational barriers, including biological heterogeneity, limited predictive power of animal models, safety concerns, and manufacturing scalability, continue to challenge clinical implementation. Emerging solutions such as AI-guided nanoparticle design, humanized disease models, and organ-on-chip systems aim to bridge these gaps. Collectively, current preclinical evidence supports nanomedicine as a central pillar of precision drug delivery, with future progress expected to focus on adaptive, multifunctional, and patient-specific platforms that align with the principles of personalized medicine.
Ashna Sureshkumar, Prakash Balu· Frontiers in Biomaterials Sc...· 0 citations
Nanoparticle-based drug delivery systems have become an important component of modern nanomedicine, enabling improved drug protection, controlled release, targeted delivery, and the modulation of pharmacokinetic behavior. Their therapeutic performance is governed by physicochemical properties such as size, shape, surface chemistry, and material composition, which influence biological interactions, biodistribution, cellular uptake, and clearance. This review examines major nanoparticle platforms, including polymeric, lipid-based, inorganic, carbon-based, and hybrid systems, together with passive and active targeting and endogenous and externally triggered release strategies. Current and emerging applications in oncology, infectious diseases, central nervous system disorders, gene therapy, and vaccines are discussed alongside theranostic and combination-delivery approaches. Particular emphasis is placed on computational modeling, artificial intelligence, and digital twins for formulation optimization and personalized nanomedicine. Key barriers to clinical translation, including manufacturing scalability, biological variability, limitations of EPR-mediated targeting, regulatory standardization, and long-term safety, are critically evaluated. Finally, emerging directions in sustainable nanomanufacturing and biomimetic delivery are discussed. By integrating biological mechanisms with computational, manufacturing, regulatory, and clinical considerations, this review provides a translational perspective on advancing nanoparticle drug-delivery systems from laboratory development toward clinical implementation.
Subin Antony Jose, Benjamin Crutchfield, M. Caballero et al.· Molecules· 0 citations
Liposomal nanocarriers are clinically established platforms for targeted drug delivery due to their biocompatibility and ability to encapsulate both hydrophilic and hydrophobic agents. However, conventional single‐drug liposomes are limited by suboptimal efficacy, systemic toxicity, and multidrug resistance. Dual‐drug‐loaded liposomes (DDLs) address these limitations by enabling co‐delivery of synergistic agents within a single nanocarrier. This review provides an integrated analysis of DDL systems, focusing on formulation design, drug loading strategies, and key physicochemical parameters governing encapsulation efficiency and controlled release. Mechanistic insights into therapeutic enhancement are highlighted, including modulation of efflux transporters, reversal of epithelial–mesenchymal transition, and synchronized intracellular delivery. The impact of ligand‐mediated functionalization on tumor targeting and cellular uptake is also critically evaluated. Unlike existing reviews, this work provides a unified framework integrating formulation design, mechanistic insights into drug synergy, and translational challenges specific to DDLs, addressing a critical gap in the existing literature. Preclinical and clinical evidence, including approved formulations such as Vyxeos, is discussed. Remaining barriers include scale‐up, reproducibility, immune interactions, and regulatory complexity. Future directions emphasize personalized and stimulus‐responsive nanomedicine for improved cancer therapy.
Neelam Sinha, Rohan Chand Sahu, Rohit Patil et al.· MedComm – Biomaterials and A...· 0 citations
Nanotechnology has become a revolutionary technology in contemporary medicine that can provide new solutions to the inefficiency of the traditional drug delivery systems. Nanoscale properties enable precise drug targeting, controlled release, enhanced bioavailability, and reduced systemic toxicity. The review gives a general description of drug delivery systems that are based on nanotechnology, with liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, and metallic nanoparticles being the main examples of nanocarriers. Critical discussions are made of their design strategies, drug loading capacities, release mechanisms and therapeutic advantages. In addition, more recent technological developments in the areas of targeted delivery, such as ligand-mediated delivery and stimuli-responsive systems, are discussed in the treatment of various diseases in cancer, infections, and neurological conditions. Despite significant advancements, there are still issues of toxicity, stability, large-scale production, and regulatory issues, which are impediments to clinical translation. In general, the field of nanotechnology offers a potential platform in improving therapeutic efficacy and development of biomaterial-based medical applications.
Shalini Tiwari, S. Kotnala, Rohinee Bhandari et al.· Trends in Biomaterials & Art...· 0 citations
Cancer remains a major global health challenge, and the limitations of conventional therapies, including systemic toxicity, drug resistance, and poor tumor selectivity, continue to drive the development of advanced nanomedicine strategies. In this context, nanocarriers offer promising opportunities to improve pharmacokinetics, enhance tumor accumulation, and enable controlled or stimuli-responsive drug release. Among them, inorganic nanoparticles (NPs) have gained considerable attention because of their structural stability, tunable surface chemistry, and multifunctional capabilities. Their performance depends on a structure–property–function relationship in which composition, morphology, porosity, degradability, and surface characteristics strongly influence interactions at the nano–bio interface. This review examines the main classes of nanoplatforms currently explored for cancer therapy, including inorganic, polymeric, lipid-based, and hybrid organic–inorganic systems. Particular attention is given to the trade-offs that define each platform in terms of loading capacity, biodegradability, multifunctionality, and translational potential. The discussion also highlights the role of predictive biological models, emphasizing that 3D spheroids, organoids, and organ-on-chip systems provide more realistic insights than conventional 2D assays for evaluating tumor penetration and microenvironment-responsive delivery. In addition, the review considers emerging directions in AI-guided nanoparticle engineerization design and natural-compound-based nanomedicines, both of which are expanding the therapeutic landscape. Overall, the field is moving toward more integrated, application-specific, and clinically translatable nanomedicine platforms capable of addressing the complex biological barriers of cancer treatment.
C. Boncristiani, F. Baldassarre, Khadija Eddahaoui et al.· Materials· 0 citations
Therapeutic glycoproteins, a pivotal class of biopharmaceuticals, have transformed modern medicine through their broad applications in oncology, immunotherapy, and infectious disease management. Their structural complexity and biological specificity make them highly effective in targeting disease pathways; however, challenges related to stability, bioavailability, and delivery efficacy limit their full potential. Recent advancements in delivery technologies have sought to address these challenges through innovative approaches such as nanotechnology-based carriers, controlled-release systems, and molecular engineering. These strategies have demonstrated the ability to enhance glycoprotein stability, optimize pharmacokinetics, and achieve targeted delivery with minimal off-target effects. This review provides a comprehensive overview of state-of-the-art lipid-based delivery systems specifically designed to overcome the unique pharmaceutical challenges associated with therapeutic glycoproteins, highlighting their design principles, formulation strategies, mechanisms of encapsulation and release, and therapeutic advantages in improving glycoprotein stability, bioavailability, targeted delivery, and treatment efficacy. In addition to surveying the current landscape, this review delves into the key challenges impeding the widespread adoption of advanced delivery systems, including immunogenicity, manufacturing scalability, and clinical translation. The review concludes with insights into emerging trends in the development of lipid-based delivery systems, positioning glycoprotein therapeutics at the forefront of innovation in biopharmaceuticals. This overview of advancements and challenges aims to provide a roadmap for future progress in the field of glycoprotein delivery and therapeutic applications.
Hamad Alrbyawi· Pharmaceutics· 0 citations
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