Cited by 1,361Advanced Drug Delivery SystemsNanoparticle-Based Drug DeliveryRNA Interference and Gene Delivery

The DOI matches its Crossref record; 269 of the 275 references it cites were found in a registry or an index.

The evolution of commercial drug delivery technologies

Vargason, Ava M., Anselmo, Aaron C., Mitragotri, Samir·2021·Nature Biomedical Engineering

Open this paper in CoChat — free account

Abstract

Drug delivery technologies have enabled the development of many pharmaceutical products that improve patient health by enhancing the delivery of a therapeutic to its target site, minimizing off-target accumulation and facilitating patient compliance. As therapeutic modalities expanded beyond small molecules to include nucleic acids, peptides, proteins and antibodies, drug delivery technologies were adapted to address the challenges that emerged. In this Review Article, we discuss seminal approaches that led to the development of successful therapeutic products involving small molecules and macromolecules, identify three drug delivery paradigms that form the basis of contemporary drug delivery and discuss how they have aided the initial clinical successes of each class of therapeutic. We also outline how the paradigms will contribute to the delivery of live-cell therapies.

Integrity signals

Registry

Crossref · 10.1038/s41551-021-00698-w

Cites

269 of 269 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00129-0 · Cited by 18,139
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Perez, J. L., Pérez Marc, G., Moreira, E. D., Zerbini, C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2034577 · Cited by 14,592
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(96)00423-1 · Cited by 11,484
Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Baden, L. R., El Sahly, H. M., Essink, B., Kotloff, K., Frey, S., Novak, R., Diemert, D., Spector, S. A., Rouphael, N., Creech, C. B., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2035389 · Cited by 10,119
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210
Stimuli-responsive nanocarriers for drug delivery
Mura, S., Nicolas, J., & Couvreur, P. (2013) · Nature Materials · doi:10.1038/nmat3776 · Cited by 6,289
Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia
Maude, S. L., Laetsch, T. W., Buechner, J., Rives, S., Boyer, M., Bittencourt, H., Bader, P., Verneris, M. R., Stefanski, H. E., Myers, G. D., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1709866 · Cited by 5,735
Liposomal drug delivery systems: From concept to clinical applications
Allen, T. M., & Cullis, P. R. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.037 · Cited by 4,839
Doxil® — The first FDA-approved nano-drug: Lessons learned
Barenholz, Y. (. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.03.020 · Cited by 4,792
Drug Delivery Systems: Entering the Mainstream
Allen, T. M., & Cullis, P. R. (2004) · Science · doi:10.1126/science.1095833 · Cited by 4,552

Show all 275 references

Research works printed but not linked: 2

Dost, F. H. Der Blutspiegel: Kinetik der Konzentrationsabläufe in der Kreislaufflüssigkeit (Georg Thieme, 1953).
DeLoach, J. R. & Sprandel, U. (eds) in Bibliotheca Haematologica Vol. 51 (Karger, 1985).

Sorted by citations

Items 101–200 of 1,000

Inflammation and Cancer: From the Development of Personalized Indicators to Novel Therapeutic Strategies
Ballerini, P., Contursi, A., Bruno, A., Mucci, M., Tacconelli, S., & Patrignani, P. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.838079 · Cited by 71
Coacervates: Recent developments as nanostructure delivery platforms for therapeutic biomolecules
Ban, E., & Kim, A. (2022) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2022.122058 · Cited by 67
Cell-penetrating peptides for transmucosal delivery of proteins
Wu, J., Roesger, S., Jones, N. B., Hu, C. J., & Li, S. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.01.038 · Cited by 70
Standardization Approaches for Extracellular Vesicle Loading with Oligonucleotides and Biologics
Roerig, J., & Schulz‐Siegmund, M. (2023) · Small · doi:10.1002/smll.202301763 · Cited by 67
Platinum(IV) and platinum(II) anticancer complexes with biologically active releasable ligands
Štarha, P., & Křikavová, R. (2023) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2023.215578 · Cited by 67
Dual-responsive nanocarriers for efficient cytosolic protein delivery and CRISPR-Cas9 gene therapy of inflammatory skin disorders
Tan, E., Wan, T. Y., Pan, Q., Duan, J., Zhang, S., Wang, R., Gao, P., Lv, J., Wang, H., Li, D., et al. (2024) · Science Advances · doi:10.1126/sciadv.adl4336 · Cited by 69
Prebiotics empower probiotics with gastrointestinal stress resistance for colon-targeted release to synergistically alleviate colitis
Ji, H., Yan, X.-C., Zhang, L., Yang, L., Xie, P., Gu, F., Bian, S., Wan, H., & Nie, S. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.01.059 · Cited by 69
Nanoengineered sonosensitive platelets for synergistically augmented sonodynamic tumor therapy by glutamine deprivation and cascading thrombosis
Zhou, L., Feng, W., Mao, Y., Chen, Y., & Zhang, X. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.11.020 · Cited by 66
“Adsorption of nanomaterials onto primitive living cells with different physiological functions through nanoengineering techniques, such as platelet (PLT) cells, can effectively solve this tough challenge owing to their innate tendencies to accumulate at tumor wounds [17], thus presenting the advantages of desirable se…”
Background
Cell-Based Drug Delivery Systems with Innate Homing Capability as a Novel Nanocarrier Platform
Choi, A., Javius-Jones, K., Hong, S., & Park, H. (2023) · International Journal of Nanomedicine · doi:10.2147/ijn.s394389 · Cited by 67
“In the past decades, drug delivery systems (DDSs) have been extensively studied to address these issues.(2) The design of the DDS aims to increase the therapeutic dose of the drug at the target site while maintaining sustained drug release.”
Background
Carbon-based nanocomposites for biomedical applications
Shin, M., Lim, J., Park, Y., Lee, J., Yoon, J., & Choi, J. (2024) · RSC Advances · doi:10.1039/d3ra08946k · Cited by 74
Designing drug delivery systems for cell therapy
Wang, L., Gao, Y., Feng, Z., Mooney, D. J., & Mitragotri, S. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00214-0 · Cited by 76
“…improve cell therapies by addressing biological challenges associated with adoptively transferred cells, such as undesired pharmacokinetics, lack of persistence of the therapeutic phenotype or functions, cell exhaustion or decreased cell viability and immunogenicity of administered cells 9 .”
Self-citation
Advanced delivery systems for peptide antibiotics
Cesaro, A., Lin, S., Pardi, N., & de la Fuente‐Núñez, C. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114733 · Cited by 67
Soft and Flexible Bioelectronic Micro‐Systems for Electronically Controlled Drug Delivery
Mariello, M., Eş, İ., & Proctor, C. M. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202302969 · Cited by 70
Dual‐Targeted Lipid Nanotherapeutic Boost for Chemo‐Immunotherapy of Cancer
Yong, S., Ramishetti, S., Goldsmith, M., Diesendruck, Y., Hazan‐Halevy, I., Chatterjee, S., Naidu, G. S., Ezra, A., & Peer, D. (2022) · Advanced Materials · doi:10.1002/adma.202106350 · Cited by 66
Nutraceutical Concepts and Dextrin-Based Delivery Systems
Hoti, G., Matencio, A., Pedrazzo, A. R., Cecone, C., Appleton, S. L., Monfared, Y. K., Caldera, F., & Trotta, F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084102 · Cited by 66
Anticancer activity of quantum size carbon dots: opportunities and challenges
Bhattacharya, T., Preetam, S., Mukherjee, S., Kar, S., Roy, D. S., Singh, H., Ghose, A., Das, T., & Mohapatra, G. (2024) · Discover Nano · doi:10.1186/s11671-024-04069-7 · Cited by 71
Advancing Proteolysis Targeting Chimera (PROTAC) Nanotechnology in Protein Homeostasis Reprograming for Disease Treatment
Wu, M., Zhao, Y., Zhang, C., & Pu, K. (2024) · ACS Nano · doi:10.1021/acsnano.4c09800 · Cited by 65
Trends in Photopolymerization 3D Printing for Advanced Drug Delivery Applications
Hu, Y., Luo, Z., & Bao, Y. (2024) · Biomacromolecules · doi:10.1021/acs.biomac.4c01004 · Cited by 74
MACHINE LEARNING IN DRUG DISCOVERY: A CRITICAL REVIEW OF APPLICATIONS AND CHALLENGES
Udegbe, F. C., Ebulue, O. R., Ebulue, C. C., & Ekesiobi, C. S. (2024) · Computer Science & IT Research Journal · doi:10.51594/csitrj.v5i4.1048 · Cited by 63
Hydrogel-forming microarray patches with solid dispersion reservoirs for transdermal long-acting microdepot delivery of a hydrophobic drug
Naser, Y. A., Tekko, I. A., Vora, L. K., Peng, K., Anjani, Q. K., Greer, B., Elliott, C. T., McCarthy, H. O., & Donnelly, R. F. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.03.003 · Cited by 62
Nanocarrier design–function relationship: The prodigious role of properties in regulating biocompatibility for drug delivery applications
Oladipo, A. O., Lebelo, S. L., & Msagati, T. A. M. (2023) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2023.110466 · Cited by 65
A Wireless Operated Flexible Bioelectronic Microneedle Patch for Actively Controlled Transdermal Drug Delivery
Jin, T., Wang, H., Ullah, I., Xie, W., Lin, T., Tan, Q., Pan, X., & Yuan, Y. (2025) · Advanced Materials · doi:10.1002/adma.202417136 · Cited by 64
Drug in Drug: A Host–Guest Formulation of Azocalixarene with Hydroxychloroquine for Synergistic Anti‐Inflammation
Li, S., Ma, R., Hu, X., Li, H., Geng, W., Kong, X., Zhang, C., & Guo, D. (2022) · Advanced Materials · doi:10.1002/adma.202203765 · Cited by 61
Self-assembling nanocarriers from engineered proteins: Design, functionalization, and application for drug delivery
Li, Y., & Champion, J. A. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114462 · Cited by 65
Plant-derived nanovesicles and therapeutic application
Jung, D., Kim, N.-E., Kim, J. H., Bae, J.-H., Jung, I.-Y., Doh, K.-W., Lee, B.-H., Kim, D., Cho, Y., & Baek, M. (2025) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2025.108832 · Cited by 63
Multimicrochannel Microneedle Microporation Platform for Enhanced Intracellular Drug Delivery
Lin, L., Wang, Y., Cai, M., Jiang, X., Hu, Y., Dong, Z., Yin, D., Liu, Y., Yang, S., Liu, Z., et al. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202109187 · Cited by 61
Bacteria extracellular vesicle as nanopharmaceuticals for versatile biomedical potential
Ho, M. Y., Liu, S., & Xing, B. (2024) · Nano Convergence · doi:10.1186/s40580-024-00434-5 · Cited by 62
Exploring Protein-Based Carriers in Drug Delivery: A Review
Ferraro, C., Dattilo, M., Patitucci, F., Prete, S., Scopelliti, G., Parisi, O. I., & Puoci, F. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16091172 · Cited by 60
“…for facing important issues such as the presence of biological barriers or immune system reactions to immunogenicity-caused harmful effects [1]. approaches for facing important issues such as the presence of biological barriers or immune system reactions to immunogenicity-caused DDSs…”
Background
Eutectogels: Recent Advances and Emerging Biological Applications
Hu, Y., Yang, W., Zhan, J., Pu, C., Zhong, L., & Hou, H. (2025) · Advanced Functional Materials · doi:10.1002/adfm.202425778 · Cited by 60
Multifunctional Layered Double Hydroxides for Drug Delivery and Imaging
Yu, S., Choi, G., & Choy, J. (2023) · Nanomaterials · doi:10.3390/nano13061102 · Cited by 59
“The primary purpose of drug-delivery systems (DDSs) is to transport and release drugs at the target site for maximum therapeutic efficacy with minimum influence on non-target sites [51].”
Background
Engineered mesenchymal stem cell-derived extracellular vesicles constitute a versatile platform for targeted drug delivery
Meng, W., Wang, L., Du, X., Xie, M., Yang, F., Li, F., Wu, Z. E., Gan, J., Wei, H., Cao, C. Q., et al. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.09.037 · Cited by 60
Chemical and biological engineering strategies to make and modify next-generation hydrogel biomaterials
Gharios, R., Francis, R. M., & DeForest, C. A. (2023) · Matter · doi:10.1016/j.matt.2023.10.012 · Cited by 60
Advancements in Skin‐Mediated Drug Delivery: Mechanisms, Techniques, and Applications
Lee, D. H., Lim, S., Kwak, S. S., & Kim, J. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202302375 · Cited by 72
Remote control of mechanochemical reactions under physiological conditions using biocompatible focused ultrasound
Yao, Y., McFadden, M. E., Luo, S. M., Barber, R. W., Kang, E., Bar‐Zion, A., Smith, C. A. B., Jin, Z., Legendre, M. G., Ling, B., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2309822120 · Cited by 58
CytoDirect: A Nucleic Acid Nanodevice for Specific and Efficient Delivery of Functional Payloads to the Cytoplasm
Lu, Y., Xu, Y., Al‐Amin, M., Jiang, S., Sample, M., Prasad, A., Stephanopoulos, N., Šulc, P., & Yan, H. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c07491 · Cited by 57
Peptide-Drug Conjugates: Design, Chemistry, and Drug Delivery System as a Novel Cancer Theranostic
Rizvi, S. F. A., Zhang, L., Zhang, H., & Fang, Q. (2024) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.3c00269 · Cited by 57
Microfluidic Preparation of Gelatin Methacryloyl Microgels as Local Drug Delivery Vehicles for Hearing Loss Therapy
Wang, J., Wang, C., Wang, Q., Zhang, Z., Wang, H., Wang, S., Chi, Z., Shang, L., Wang, W., & Shu, Y. (2022) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.2c11647 · Cited by 56
Stabilizing RNA Nanovaccines with Transformable Hyaluronan Dynamic Hydrogel for Durable Cancer Immunotherapy
Jia, F., Huang, W., Yin, Y., Jiang, Y., Yang, Q., Huang, H., Nie, G., & Wang, H. (2022) · Advanced Functional Materials · doi:10.1002/adfm.202204636 · Cited by 56
Design and characterization of matrix metalloproteinase-responsive hydrogels for the treatment of inflammatory skin diseases
Noddeland, H. K., Lind, M. L., Jensen, L. B., Petersson, K., Skak‐Nielsen, T., Larsen, F. H., Malmsten, M., & Heinz, A. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.12.015 · Cited by 56
Emerging frontiers in drug delivery with special focus on novel techniques for targeted therapies
Yu, L., Liu, S., Jia, S., & Xu, F. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115049 · Cited by 59
Enhancing drug loading and release with hydroxyapatite nanoparticles for efficient drug delivery: A review synthesis methods, surface ion effects, and clinical prospects
Safitri, N., Rauf, N., & Tahir, D. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.105092 · Cited by 56
Targeted protein delivery based on stimuli‐triggered nanomedicine
Liu, J., Zhou, Y., Lyu, Q., Yao, X., & Wang, W. (2023) · Exploration · doi:10.1002/exp.20230025 · Cited by 56
Personalized Medicine in Mitochondrial Health and Disease: Molecular Basis of Therapeutic Approaches Based on Nutritional Supplements and Their Analogs
Tragni, V., Primiano, G., Tummolo, A., Beltrame, L. C., Piana, G. L., Sgobba, M. N., Cavalluzzi, M. M., Paterno, G., Gorgoglione, R., Volpicella, M., et al. (2022) · Molecules · doi:10.3390/molecules27113494 · Cited by 55
Nuclear SPHK2/S1P induces oxidative stress and NLRP3 inflammasome activation via promoting p53 acetylation in lipopolysaccharide-induced acute lung injury
Gong, L., Shen, Y., Wang, S., Wang, X., Ji, H., Wu, X., Hu, L., & Zhu, L. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01320-5 · Cited by 59
“Although it may have potential therapeutic implications, many targeted antibodies and small-molecule inhibitors are also associated with organ impairment because of off-target toxicity [40].”
Background
Nanomaterial-Driven Precision Immunomodulation: A New Paradigm in Therapeutic Interventions
Aljabali, A. A. A., Obeid, M. A., Gammoh, O., El‐Tanani, M., Mishra, V. K., Mishra, Y., Kapre, S., Palakurthi, S. S., Hassan, S. S., Nawn, D., et al. (2024) · Cancers · doi:10.3390/cancers16112030 · Cited by 62
“To fully realize this potential, it is crucial to address the challenges associated with achieving the desired release profiles, minimizing off-target effects, and ensuring optimal biocompatibility in triggered-release systems [139].”
Background
Rhamnolipid-coated W/O/W double emulsion nanoparticles for efficient delivery of doxorubicin/erlotinib and combination chemotherapy
Lee, Y., Lee, D., Park, E. Y., Jang, S.-Y., Cheon, S. Y., Han, S., & Koo, H. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-01160-4 · Cited by 54
Red Blood Cell Inspired Strategies for Drug Delivery: Emerging Concepts and New Advances
Zhang, E., Phan, P., Algarni, H. A., & Zhao, Z. (2022) · Pharmaceutical Research · doi:10.1007/s11095-022-03328-5 · Cited by 56
Biodegradable silica nanocapsules enable efficient nuclear-targeted delivery of native proteins for cancer therapy
Du, W., Du, S., Dong, X., Bai, H., Jiang, J., Hao, S., Yang, F., Xiao, Q., Zhang, B., Ge, J., et al. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122000 · Cited by 54
Sterically chained amino acid-rich water-soluble carbon quantum dots as a robust tumor-targeted drug delivery platform
Xie, W., Wang, H., Xu, H., Su, W., Yuan, T., Chang, J., Bai, Y., Fan, Y., Zhang, Y., Li, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57531-0 · Cited by 58
Selenium-Based Drug Development for Antioxidant and Anticancer Activity
Debnath, S., Agarwal, A., Kumar, N. R., & Bedi, A. (2022) · Future Pharmacology · doi:10.3390/futurepharmacol2040036 · Cited by 55
Targeted Delivery of Zinc Ion Derived by Pseudopolyrotaxane Gel Polymer Electrolyte for Long-Life Zn Anode
Wu, K., Zhan, S., Liu, W., Liu, X., Ning, F., Liu, Y., Zhang, J., & Jin, Y. (2023) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.2c20194 · Cited by 53
Advances in nanotechnology versus stem cell therapy for the theranostics of Huntington's disease
Channa, G. M., Hassan, D., Zeeshan, M., Ruiz-Pulido, G., Ebrahimi, N., Mobashar, A., Pourmadadi, M., Rahdar, A., Sargazi, S., Fathi‐karkan, S., et al. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.104774 · Cited by 53
β-Glucan—A promising immunocyte-targeting drug delivery vehicle: Superiority, applications and future prospects
He, L., Zhu, Z., & Qi, C. (2024) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2024.122252 · Cited by 55
Localized, on-demand, sustained drug delivery from biopolymer-based materials
Wu, J., Shaidani, S., Theodossiou, S. K., Hartzell, E. J., & Kaplan, D. L. (2022) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2022.2110582 · Cited by 53
“Challenges with local delivery of small molecules, protein and peptides, antibodies, and nucleic acids [64].”
Background
Peptide-mediated liquid–liquid phase separation and biomolecular condensates
Li, G., Yuan, C., & Yan, X. (2025) · Soft Matter · doi:10.1039/d4sm01477d · Cited by 53
Nonviral delivery systems for antisense oligonucleotide therapeutics
Huang, S. Q., Hao, X., Li, Y., Wu, J., Xiang, D., & Luo, S. (2022) · Biomaterials Research · doi:10.1186/s40824-022-00292-4 · Cited by 53
Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery
Brar, H. K., Jose, J., Wu, Z., & Sharma, M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics15010059 · Cited by 50
Supramolecular nanoarchitectonics of phenolic-based nanofiller for controlled diffusion of versatile drugs in hydrogels
Pan, J., Liao, H., Gong, G., He, Y., Wang, Q., Qin, L., Zhang, Y., Ejima, H., Tardy, B. L., Richardson, J. J., et al. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.07.003 · Cited by 50
Rescue of dendritic cells from glycolysis inhibition improves cancer immunotherapy in mice
Inamdar, S., Suresh, A. P., Mangal, J. L., Ng, N. D., Sundem, A., Wu, C. W., Lintecum, K., Thumsi, A., Khodaei, T., Halim, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41016-z · Cited by 50
“However,these metabolites are small molecules that get consumed or diffuse away after administration in vivo 17,18 .”
A novel ROS-activable self-immolative prodrug for tumor-specific amplification of oxidative stress and enhancing chemotherapy of mitoxantrone
Zhang, H., Chen, W., Wang, J., Du, W., Wang, B., Song, L., Hu, Y. Z., & Ma, X. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121954 · Cited by 50
Accelerating therapeutic protein design with computational approaches toward the clinical stage
Chen, Z., Wang, X., Chen, X., Huang, J., Wang, C., Wang, J., & Wang, Z. (2023) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2023.04.027 · Cited by 49
“Although they offer high therapeutic efficacy and minimal side effects, their stability in biological environments is low, resulting in poor oral bioavailability [60].”
Background
More Than Pigments: The Potential of Astaxanthin and Bacterioruberin-Based Nanomedicines
Morilla, M. J., Ghosal, K., & Romero, E. L. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071828 · Cited by 50
“Nanomedicines consist of nanostructures loaded with different types of molecules; the first nanomedicine launched to the pharmaceutical market in 1995 was pegylated liposomal doxorubicin (Doxyl/Caelyx) [185].”
Background
Site-selected in situ polymerization for living cell surface engineering
Zhong, Y., Xu, L., Yang, C., Xu, L., Wang, G., Guo, Y., Cheng, S., Tian, X., Wang, C., Xie, R., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43161-x · Cited by 49
pNIPAm-Based pH and Thermoresponsive Copolymer Hydrogel for Hydrophobic and Hydrophilic Drug Delivery
Mohan, A., Santhamoorthy, M., Phan, T. T. V., & Kim, S. (2024) · Gels · doi:10.3390/gels10030184 · Cited by 49
“Block copolymers have been identified as an effective drug carrier among a variety of developed polymeric materials [3,4].”
Background
Nanofibrous supramolecular peptide hydrogels for controlled release of small-molecule drugs and biologics
Pogostin, B. H., Wu, S. X., Swierczynski, M. J., Pennington, C. L., Li, S., Vohidova, D., Seeley, E. H., Agrawal, A., Tang, C., Yu, M. H., et al. (2025) · Nature Nanotechnology · doi:10.1038/s41565-025-01981-6 · Cited by 53
“Drug delivery systems can enhance the therapeutic efficacy of pharmaceutical drugs by maintaining drug concentrations within narrow therapeutic windows, thereby extending the duration of drug exposure while alleviating side effects 1 .”
“One Stone, Four Birds” Ion Engineering to Fabricate Versatile Core–Shell Organosilica Nanoparticles for Intelligent Nanotheranostics
Yan, S., Sun, P., Niu, N., Zhang, Z., Xu, W., Zhao, S., Wang, L., Wang, D., & Tang, B. Z. (2022) · ACS Nano · doi:10.1021/acsnano.2c03550 · Cited by 48
Biotin conjugates in targeted drug delivery: is it mediated by a biotin transporter, a yet to be identified receptor, or (an)other unknown mechanism(s)?
Tripathi, R. S., Guglani, A., Ghorpade, R., & Wang, B. (2023) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2023.2276663 · Cited by 51
Recent Developments in Metallic Degradable Micromotors for Biomedical and Environmental Remediation Applications
Dutta, S., Noh, S., Sanchis‐Gual, R., Chen, X., Pané, S., Nelson, B. J., & Choi, H. (2023) · Nano-Micro Letters · doi:10.1007/s40820-023-01259-3 · Cited by 49
“First-generation drug carriers relied on passive diffusion and natural body fluid flow for drug delivery [51–53].”
Background
Unraveling the Role of the Tumor Extracellular Matrix to Inform Nanoparticle Design for Nanomedicine
Cassani, M., Fernandes, S., Pagliari, S., Cavalieri, F., Caruso, F., & Forte, G. (2025) · Advanced Science · doi:10.1002/advs.202409898 · Cited by 48
Polymeric Systems for the Controlled Release of Flavonoids
Pecorini, G., Ferraro, E., & Puppi, D. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020628 · Cited by 50
“, functionalization of other polymers with PEG, has become very important since it permits the extension of the circulation half-life of many proteins and reduces their immunogenicity [38].”
BackgroundInfluential
Amyloid-β/Tau burden and neuroinflammation dual-targeted nanomedicines synergistically restore memory and recognition of Alzheimer’s disease mice
Zhang, L. L., Hou, S., Movahedi, F., Li, Z., Li, L., Hu, J., Jia, Y., Huang, Y., Zhu, J., Sun, X., et al. (2023) · Nano Today · doi:10.1016/j.nantod.2023.101788 · Cited by 50
Role of long non-coding RNAs in cancer: From subcellular localization to nanoparticle-mediated targeted regulation
Wei, C., Ya, X., Shen, Q., Li, R., Xiao, X., Saw, P. E., & Xu, X. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.07.009 · Cited by 51
A review on tunable multi-functional Prussian blue nanoparticles; their promising biological applications & future directions
Shukla, M., Verma, N. V., Mohanta, Z., Tripathi, S., & Pandya, A. (2023) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2023.215414 · Cited by 47
Synthetic Biology‐Based Engineering Cells for Drug Delivery
Yi, W., Hu, S., Qian, X., Yan, W., & Li, Y. (2025) · Exploration · doi:10.1002/exp.20240095 · Cited by 49
“However, their complex isolation and purification, strong immunogenicity, intricate crystal structure, and challenges in crossing biological barriers have limited their application [47–49].”
Dual tumor- and subcellular-targeted photodynamic therapy using glucose-functionalized MoS2 nanoflakes for multidrug-resistant tumor ablation
Xu, S., Zhang, P., Heing‐Becker, I., Zhang, J., Tang, P., Bej, R., Bhatia, S., Zhong, Y., & Haag, R. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121844 · Cited by 46
Recent advances in extracellular vesicle-based organic nanotherapeutic drugs for precision cancer therapy
Nguyen, V.-N., Dao, T. N. T., Cho, M., Jeong, H., Nguyen-Le, M.-T., Shin, Y. M., & Yoon, J. (2022) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2022.215006 · Cited by 46
A Bimetallic Polymerization Network for Effective Increase in Labile Iron Pool and Robust Activation of cGAS/STING Induces Ferroptosis‐Based Tumor Immunotherapy
Wang, Z., Zhou, P., Li, Y., Zhang, D., Chu, F., Feng, Y., Pan, B., & Gao, F. (2023) · Small · doi:10.1002/smll.202308397 · Cited by 46
Organ/Cell-Selective Intracellular Delivery of Biologics via N-Acetylated Galactosamine-Functionalized Polydisulfide Conjugates
Lu, J., Dai, Y., He, Y., Zhang, T., Zhang, J., Chen, X., Jiang, C., & Lu, H. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.3c11914 · Cited by 47
Polymer-mediated protein/peptide therapeutic stabilization: Current progress and future directions
Sivasankaran, R. P., Snell, K., Kunkel, G. E., Georgiou, P. G., Puente, E. G., & Maynard, H. D. (2024) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2024.101867 · Cited by 54
Overcoming Cancer Drug Resistance with Nanoparticle Strategies for Key Protein Inhibition
Yoo, H., Kim, Y., Kim, J., Cho, H., & Kim, K. (2024) · Molecules · doi:10.3390/molecules29173994 · Cited by 50
Recent Advances in Degradable Biomedical Polymers for Prevention, Diagnosis and Treatment of Diseases
Zhang, S., Fang, H., & Tian, H. (2024) · Biomacromolecules · doi:10.1021/acs.biomac.4c01193 · Cited by 49
Regenerative medicine: Hydrogels and mesoporous silica nanoparticles
Pablos, J. L., Lozano, D., Manzano, M., & Vallet‐Regí, M. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101342 · Cited by 46
Delivering on the promise of recombinant silk-inspired proteins for drug delivery
González‐Obeso, C., Hartzell, E. J., Scheel, R. A., & Kaplan, D. L. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114622 · Cited by 44
Phosphorothioated DNA Engineered Liposomes as a General Platform for Stimuli‐Responsive Cell‐Specific Intracellular Delivery and Genome Editing
An, Y., Chen, X., He, J., Ge, Y., Liu, Q. L., Men, D., Xu, K., & Li, D. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202303973 · Cited by 47
Satellite‐Type Sulfur Atom Distribution in Trithiocarbonate Bond‐Bridged Dimeric Prodrug Nanoassemblies: Achieving Both Stability and Activatability
Li, L., Liu, T., Zuo, S., Li, Y., Zhao, E., Lu, Q., Wang, D., Sun, Y., He, Z., Sun, B., et al. (2023) · Advanced Materials · doi:10.1002/adma.202310633 · Cited by 45
Exquisite Vesicular Nanomedicine by Paclitaxel Mediated Co‐assembly with Camptothecin Prodrug
Zhou, Z., Du, C., Zhang, Q., Yu, G., Zhang, F., & Chen, X. S. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202108658 · Cited by 44
Targeting ROS-induced osteoblast senescence and RANKL production by Prussian blue nanozyme based gene editing platform to reverse osteoporosis
Li, K., Hu, S., Huang, J., Shi, Y., Lin, W., Liu, X., Mao, W., Wu, C., Pan, C., Xu, Z., et al. (2023) · Nano Today · doi:10.1016/j.nantod.2023.101839 · Cited by 43
Metal‐Phenolic Network Directed Coating of Single Probiotic Cell Followed by Photoinitiated Thiol‐Ene Click Fortification to Enhance Oral Therapy
Fang, T., & Liu, S. (2023) · Small · doi:10.1002/smll.202308146 · Cited by 44
Metal–Phenolic‐Mediated Assembly of Functional Small Molecules into Nanoparticles: Assembly and Bioapplications
Chen, J., Cortez‐Jugo, C., Kim, C., Lin, Z., Wang, T., Rose, R. D., Xu, W., Wang, Z., Gu, Y., & Caruso, F. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202319583 · Cited by 44
Tailoring drug delivery systems by microfluidics for tumor therapy
Zhang, Q., Kuang, G., Wang, L., Fan, L., & Zhao, Y. (2024) · Materials Today · doi:10.1016/j.mattod.2024.01.004 · Cited by 45
Oral targeted drug delivery to post-gastrointestinal sites
Han, R., He, H., Lü, Y., Lu, H., Shen, S., & Wu, W. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.04.047 · Cited by 46
Engineered multi-domain lipid nanoparticles for targeted delivery
Liu, Z., Chen, J., Xu, M., Ho, S., Wei, Y., Ho, H., & Yong, K. (2025) · Chemical Society Reviews · doi:10.1039/d4cs00891j · Cited by 63
Designer Liposomic Nanocarriers Are Effective Biofilm Eradicators
Kluzek, M., Oppenheimer‐Shaanan, Y., Dadosh, T., Morandi, M. I., Avinoam, O., Raanan, C., Goldsmith, M., Goldberg, R., & Klein, J. E. (2022) · ACS Nano · doi:10.1021/acsnano.2c04232 · Cited by 43
Mechanical stimulation on a microfluidic device to highly enhance small extracellular vesicle secretion of mesenchymal stem cells
Hao, R., Hu, S., Zhang, H., Chen, X., Yu, Z., Ren, J., Guo, H., & Yang, H. (2022) · Materials Today Bio · doi:10.1016/j.mtbio.2022.100527 · Cited by 46
“NCT04084951), generating engineered cell vaccines for cancer immunotherapy ex vivo [58,59].”
Background
The potential application of encapsulated exosomes: A new approach to increase exosomes therapeutic efficacy
Hazrati, A., Mirsanei, Z., Heidari, N., Malekpour, K., Rahmani-Kukia, N., Abbasi, A., & Soudi, S. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114615 · Cited by 43
Storming the gate: New approaches for targeting the dynamic tight junction for improved drug delivery
Ramirez-Velez, I., & Belardi, B. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114905 · Cited by 46
Reactive Oxygen Species-Sensitive Biodegradable Mesoporous Silica Nanoparticles Harboring TheraVac Elicit Tumor-Specific Immunity for Colon Tumor Treatment
Huang, Y., Nahar, S., Alam, M. M., Hu, S., McVicar, D. W., & Yang, D. (2023) · ACS Nano · doi:10.1021/acsnano.3c03195 · Cited by 43
Polymer mechanochemistry in drug delivery: From controlled release to precise activation
Shi, Z., Hu, Y. M., & Li, X. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.10.042 · Cited by 44
Potentials of ionic liquids to overcome physical and biological barriers
Beaven, E., Kumar, R., An, J. M., Mendoza, H., Sutradhar, S. C., Choi, W., Narayan, M., Lee, Y.-K., & Nurunnabi, M. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115157 · Cited by 46
A battery-free nanofluidic intracellular delivery patch for internal organs
Yin, D., Wang, P., Hao, Y., Yue, W. W., Jiang, X., Yao, K., Wang, Y., Hang, X., Xiao, A., Zhou, J., et al. (2025) · Nature · doi:10.1038/s41586-025-08943-x · Cited by 48

Authors: Vargason, A. M., Anselmo, A. C., & Mitragotri, S.
Affiliations: University of North Carolina at Chapel Hill (US)
Harvard University (US)
Corresponding author: Mitragotri, Samir
ORCID: Vargason, Ava M.
Anselmo, Aaron C.
Mitragotri, Samir
Venue: Nature Biomedical Engineering
Publisher: Springer Science and Business Media LLC
Published: 2021-04-01
Volume: 5
Issue: 9
Pages: 951-967
ISSN: 2157-846X (ISSN-L)
DOI: 10.1038/s41551-021-00698-w
OpenAlex: W3143156272
Cited by: 1,361
References: 275
Citations by year: 2026: 170 · 2025: 314 · 2024: 366 · 2023: 293 · 2022: 170 · 2021: 48
FWCI: 19.23
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Biomedical Engineering (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation (DGE-1650116)
U.S. Department of Health & Human Services | National Institutes of Health (R35GM137898, 1R01HL143806-01)
United States Department of Defense | Defense Threat Reduction Agency (HDTRA1-15-1-0045)
U.S. Department of Defense (W81XWH-19-2-0011)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords: drug delivery technology, small molecules, macromolecules, nucleic acids, proteins, immunoglobulins, medication adherence
MeSH terms: Pharmaceutical Preparations, Humans, Nucleic Acids, Peptides, Proteins, Drug Delivery Systems

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The evolution of commercial drug delivery technologies

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks