Drug delivery interfaces in the 21st century: from science fiction ideas to viable technologies.

Early science fiction envisioned the future of drug delivery as targeted micrometer-scale submarines and "cyborg" body parts. Here we describe the progression of the field toward technologies that are now beginning to capture aspects of this early vision. Specifically, we focus on the two most prominent types of systems in drug delivery: the intravascular micro/nano drug carriers for delivery to the site of pathology and drug-loaded implantable devices that facilitate release with the predefined kinetics or in response to a specific cue. We discuss the unmet clinical needs that inspire these designs, the physiological factors that pose difficult challenges for their realization, and viable technologies that promise robust solutions. We also offer a perspective on where drug delivery may be in the next 50 years based on expected advances in material engineering and in the context of future diagnostics.

[1]  J. Carmena Advances in Neuroprosthetic Learning and Control , 2013, PLoS biology.

[2]  Daniel G Anderson,et al.  Injectable nano-network for glucose-mediated insulin delivery. , 2013, ACS nano.

[3]  Dennis E Discher,et al.  Minimal " Self " Peptides That Inhibit Phagocytic Clearance and Enhance Delivery of Nanoparticles References and Notes , 2022 .

[4]  Z. John Shen,et al.  Review of Silicon Power Semiconductor Technologies for Power Supply on Chip and Power Supply in Package Applications , 2013, IEEE Transactions on Power Electronics.

[5]  B. Brown,et al.  Expanded applications, shifting paradigms and an improved understanding of host-biomaterial interactions. , 2013, Acta biomaterialia.

[6]  M. Masuda,et al.  Proteomic approaches to the discovery of cancer biomarkers for early detection and personalized medicine. , 2013, Japanese journal of clinical oncology.

[7]  P. Gualtieri,et al.  Clustering and turbulence modulation in particle laden shear flows , 2011, Journal of Fluid Mechanics.

[8]  Arianna Menciassi,et al.  Wearable and implantable pancreas substitutes , 2013, Journal of Artificial Organs.

[9]  Sergio Martinoia,et al.  Modular Neuronal Assemblies Embodied in a Closed-Loop Environment: Toward Future Integration of Brains and Machines , 2012, Front. Neural Circuits.

[10]  Samuel I Stupp,et al.  Advances in cryogenic transmission electron microscopy for the characterization of dynamic self-assembling nanostructures. , 2012, Current opinion in colloid & interface science.

[11]  Rajiv Ranganathan,et al.  The Body-Machine Interface: A New Perspective on an Old Theme , 2012, Journal of motor behavior.

[12]  D. Ingber,et al.  Shear-Activated Nanotherapeutics for Drug Targeting to Obstructed Blood Vessels , 2012, Science.

[13]  Jianzhong Lin,et al.  Nanoparticle Migration in a Fully Developed Turbulent Pipe Flow Considering the Particle Coagulation , 2012 .

[14]  Mihai Irimia-Vladu,et al.  Green and biodegradable electronics , 2012 .

[15]  C. Bettinger,et al.  Biomaterials‐Based Electronics: Polymers and Interfaces for Biology and Medicine , 2012, Advanced healthcare materials.

[16]  Robert Langer,et al.  Materials for Diabetes Therapeutics , 2012, Advanced healthcare materials.

[17]  Percy A. Knolle,et al.  Living in the liver: hepatic infections , 2012, Nature Reviews Immunology.

[18]  Robert Langer,et al.  First-in-Human Testing of a Wirelessly Controlled Drug Delivery Microchip , 2012, Science Translational Medicine.

[19]  S. Wan,et al.  Effect of teriparatide on bone mineral density and fracture in postmenopausal osteoporosis: meta‐analysis of randomised controlled trials , 2012, International journal of clinical practice.

[20]  N. Jørgensen,et al.  Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans , 2012, Scandinavian journal of clinical and laboratory investigation.

[21]  S M Moghimi,et al.  Factors controlling nanoparticle pharmacokinetics: an integrated analysis and perspective. , 2012, Annual review of pharmacology and toxicology.

[22]  P. Flatt,et al.  Emerging Applications of Metabolomic and Genomic Profiling in Diabetic Clinical Medicine , 2011, Diabetes Care.

[23]  D. Gold,et al.  Factors Associated with Persistence with Teriparatide Therapy: Results from the DANCE Observational Study. , 2011, Journal of osteoporosis.

[24]  Chao Zhong,et al.  A polysaccharide bioprotonic field-effect transistor. , 2011, Nature communications.

[25]  V. Yang,et al.  Magnetically-enabled and MR-monitored selective brain tumor protein delivery in rats via magnetic nanocarriers. , 2011, Biomaterials.

[26]  Mary E Napier,et al.  More effective nanomedicines through particle design. , 2011, Small.

[27]  Ronnie H. Fang,et al.  Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform , 2011, Proceedings of the National Academy of Sciences.

[28]  D. Patel,et al.  Principles of pharmacology. , 2011, Pediatric clinics of North America.

[29]  Joseph M. DeSimone,et al.  Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles , 2011, Proceedings of the National Academy of Sciences.

[30]  Patrick A Tresco,et al.  Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays. , 2011, Progress in brain research.

[31]  Gerd Schneider,et al.  Three-dimensional cellular ultrastructure resolved by X-ray microscopy , 2010, Nature Methods.

[32]  Justin A. Blanco,et al.  Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics. , 2010, Nature materials.

[33]  M. Berggren,et al.  Organic electronics for precise delivery of neurotransmitters to modulate mammalian sensory function. , 2009, Nature materials.

[34]  Richard D. Leapman,et al.  Nanoscale 3D cellular imaging by axial scanning transmission electron tomography , 2009, Nature Methods.

[35]  Parag Aggarwal,et al.  Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. , 2009, Advanced drug delivery reviews.

[36]  Giovanni De Micheli,et al.  An Outlook on Design Technologies for Future Integrated Systems , 2009, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[37]  F. Collins,et al.  The HapMap and genome-wide association studies in diagnosis and therapy. , 2009, Annual review of medicine.

[38]  P. Roschger,et al.  Treatment of Osteoporosis with Parathyroid Hormone and Teriparatide , 2009, Calcified Tissue International.

[39]  Andrew Leis,et al.  Visualizing cells at the nanoscale. , 2009, Trends in biochemical sciences.

[40]  G. Woodruff,et al.  BLOOD FLOW IN ARTERIES , 2009 .

[41]  H. Merkle,et al.  PEGylation as a tool for the biomedical engineering of surface modified microparticles. , 2008, Journal of pharmaceutical sciences.

[42]  M. McGirt,et al.  Use of Gliadel (BCNU) Wafer in the Surgical Treatment of Malignant Glioma: A 10-Year Institutional Experience , 2008, Annals of Surgical Oncology.

[43]  David F. Williams On the mechanisms of biocompatibility. , 2008, Biomaterials.

[44]  Dong-Yol Yang,et al.  Advances in 3D nano/microfabrication using two-photon initiated polymerization , 2008 .

[45]  James M. Anderson,et al.  Foreign body reaction to biomaterials. , 2008, Seminars in immunology.

[46]  Joseph M DeSimone,et al.  Shape-specific, monodisperse nano-molding of protein particles. , 2008, Journal of the American Chemical Society.

[47]  B. Clarke,et al.  Effect of Recombinant Human Parathyroid Hormone (1-84) on Vertebral Fracture and Bone Mineral Density in Postmenopausal Women with Osteoporosis: A Randomized Trial , 2008 .

[48]  M. Kameneva,et al.  Mechanical degradation of drag reducing polymers in suspensions of blood cells and rigid particles. , 2008, Biorheology.

[49]  V. Lukyanenko Delivery of nano-objects to functional sub-domains of healthy and failing cardiac myocytes. , 2007, Nanomedicine.

[50]  James G. Grote,et al.  Organic field-effect transistors and memory elements using deoxyribonucleic acid (DNA) gate dielectric , 2007 .

[51]  Georg Jakopic,et al.  Two-photon 3D lithography: A Versatile Fabrication Method for Com- plex 3D Shapes and Optical Interconnects within the Scope of Innovative Industrial Applications , 2007 .

[52]  M. Bawendi,et al.  Renal clearance of quantum dots , 2007, Nature Biotechnology.

[53]  N. Laperriere,et al.  Gliadel wafers in the treatment of malignant glioma: a systematic review , 2007, Current oncology.

[54]  D. Northfelt,et al.  Pegylated liposomal doxorubicin in the treatment of AIDS-related Kaposi’s sarcoma , 2007, International journal of nanomedicine.

[55]  David B Resnik,et al.  Ethics in nanomedicine. , 2007, Nanomedicine.

[56]  S. Libutti,et al.  Pulsed-High Intensity Focused Ultrasound and Low Temperature–Sensitive Liposomes for Enhanced Targeted Drug Delivery and Antitumor Effect , 2007, Clinical Cancer Research.

[57]  D. Discher,et al.  Shape effects of filaments versus spherical particles in flow and drug delivery. , 2007, Nature nanotechnology.

[58]  R. Lindsay,et al.  Effect of Recombinant Human Parathyroid Hormone (1-84) on Vertebral Fracture and Bone Mineral Density in Postmenopausal Women with Osteoporosis , 2007, Annals of Internal Medicine.

[59]  Dong-Yol Yang,et al.  Ultraprecise microreproduction of a three-dimensional artistic sculpture by multipath scanning method in two-photon photopolymerization , 2007 .

[60]  Victor Frenkel,et al.  Pulsed-high intensity focused ultrasound enhanced tPA mediated thrombolysis in a novel in vivo clot model, a pilot study. , 2007, Thrombosis research.

[61]  Robin L. Jones,et al.  Anthracycline cardiotoxicity , 2006, Expert opinion on drug safety.

[62]  Rein V. Ulijn,et al.  Enzyme-responsive materials: a new class of smart biomaterials , 2006 .

[63]  Robert Langer,et al.  Nanoparticle–aptamer bioconjugates for cancer targeting , 2006, Expert opinion on drug delivery.

[64]  V. Frenkel,et al.  Delivery of liposomal doxorubicin (Doxil) in a breast cancer tumor model: investigation of potential enhancement by pulsed-high intensity focused ultrasound exposure. , 2006, Academic radiology.

[65]  John T Santini,et al.  Chronic, programmed polypeptide delivery from an implanted, multireservoir microchip device , 2006, Nature Biotechnology.

[66]  Dakrong Pissuwan,et al.  Therapeutic possibilities of plasmonically heated gold nanoparticles. , 2006, Trends in biotechnology.

[67]  R. Hovorka Continuous glucose monitoring and closed‐loop systems , 2006, Diabetic medicine : a journal of the British Diabetic Association.

[68]  J. Reginster,et al.  Osteoporosis: a still increasing prevalence. , 2005, Bone.

[69]  Z. Ram,et al.  Gliadel® wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial , 2006, Acta Neurochirurgica.

[70]  John T Santini,et al.  Electrothermally activated microchips for implantable drug delivery and biosensing. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[71]  R. Mebius,et al.  Structure and function of the spleen , 2005, Nature Reviews Immunology.

[72]  Joseph M DeSimone,et al.  Direct fabrication and harvesting of monodisperse, shape-specific nanobiomaterials. , 2005, Journal of the American Chemical Society.

[73]  C. Porter,et al.  Subcutaneous drug delivery and the role of the lymphatics. , 2005, Drug discovery today. Technologies.

[74]  R. Langer,et al.  Smart Biomaterials , 2004, Science.

[75]  D. P. O'Neal,et al.  Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. , 2004, Cancer letters.

[76]  R. Langer,et al.  Designing materials for biology and medicine , 2004, Nature.

[77]  A. Santoro,et al.  Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[78]  Liying Wang,et al.  The Transport Barrier of Epithelia: A Comparative Study on Membrane Permeability and Charge Selectivity in the Rabbit , 1992, Pharmaceutical Research.

[79]  C. Binder,et al.  Pharmacokinetics of continuous subcutaneous insulin infusion , 1983, Diabetologia.

[80]  Robert Langer,et al.  Multi-pulse drug delivery from a resorbable polymeric microchip device , 2003, Nature materials.

[81]  Z. Ram,et al.  A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. , 2003, Neuro-oncology.

[82]  Jayanth Panyam,et al.  Biodegradable nanoparticles for drug and gene delivery to cells and tissue. , 2003, Advanced drug delivery reviews.

[83]  M. Rubin,et al.  New anabolic therapies in osteoporosis , 2002, Endocrinology and metabolism clinics of North America.

[84]  E. Beard,et al.  The American Society of Health System Pharmacists. , 2001, JONA's Healthcare Law, Ethics, and Regulation.

[85]  M. Swartz,et al.  The physiology of the lymphatic system. , 2001, Advanced drug delivery reviews.

[86]  H. Maeda The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. , 2001, Advances in enzyme regulation.

[87]  C. E. Stiles,et al.  Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density. , 2000, Journal of biomedical materials research.

[88]  R. Müller,et al.  Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[89]  R Panchagnula,et al.  Biopharmaceutics and pharmacokinetics in drug research. , 2000, International journal of pharmaceutics.

[90]  E. Bonora,et al.  Fasting plasma glucose variability predicts 10-year survival of type 2 diabetic patients: the Verona Diabetes Study. , 2000, Diabetes care.

[91]  W. Duckworth,et al.  Insulin degradation: progress and potential. , 1998, Endocrine reviews.

[92]  W. Rodrigueza,et al.  Structural and metabolic consequences of liposome-lipoprotein interactions. , 1998, Advanced Drug Delivery Reviews.

[93]  R. Jain,et al.  Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[94]  R. Lindsay,et al.  Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis , 1997, The Lancet.

[95]  H. D. Liggitt,et al.  Factors influencing the efficiency of cationic liposome-mediated intravenous gene delivery , 1997, Nature Biotechnology.

[96]  R Langer,et al.  Characterization of glucose-mediated insulin release from implantable polymers. , 1996, Journal of pharmaceutical sciences.

[97]  P. Volberding,et al.  Doxorubicin Encapsulated in Liposomes Containing Surface‐Bound Polyethylene Glycol: Pharmacokinetics, Tumor Localization, and Safety in Patients with AIDS‐Related Kaposi's Sarcoma , 1996, Journal of clinical pharmacology.

[98]  Y. Barenholz,et al.  Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. , 1994, Cancer research.

[99]  和田 八三久 Materials science. , 1973, Science.

[100]  G L Amidon,et al.  Absorption of peptide and peptidomimetic drugs. , 1994, Annual review of pharmacology and toxicology.

[101]  J. Hock,et al.  Effects of continuous and intermittent administration and inhibition of resorption on the anabolic response of bone to parathyroid hormone , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[102]  J. Kost,et al.  Responsive polymer systems for controlled delivery of therapeutics. , 1992, Trends in biotechnology.

[103]  S. Davis,et al.  Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating. , 1991, Biochemical and biophysical research communications.

[104]  R. Langer Polymer implants for drug delivery in the brain , 1991 .

[105]  C. Haanen,et al.  Clinical Pharmacokinetics of Doxorubicin , 1988, Clinical pharmacokinetics.

[106]  E. Edelman,et al.  Controlled Release of Insulin From Polymer Matrices: Control of Diabetes in Rats , 1986, Diabetes.

[107]  F. Bellisle,et al.  Cephalic phase of insulin secretion and food stimulation in humans: a new perspective. , 1985, The American journal of physiology.

[108]  T. M. Hayes,et al.  COMPARATIVE STUDY OF SUBCUTANEOUS, INTRAMUSCULAR, AND INTRAVENOUS ADMINISTRATION OF HUMAN INSULIN , 1981, The Lancet.

[109]  J. Wagner,et al.  History of pharmacokinetics. , 1981, Pharmacology & therapeutics.

[110]  R. Langer,et al.  Polymers for the sustained release of proteins and other macromolecules , 1976, Nature.

[111]  H N Sabbah,et al.  Turbulent Blood Flow in the Ascending Aorta of Humans with Normal and Diseased Aortic Valves , 1976, Circulation research.

[112]  D. Long,et al.  Silicone Rubber: A New Diffusion Property Useful for General Anesthesia , 1966, Science.

[113]  Duran Cg,et al.  COMBINING THE ANTIDEPRESSANT DRUGS. , 1965 .

[114]  J. Folkman,et al.  THE USE OF SILICONE RUBBER AS A CARRIER FOR PROLONGED DRUG THERAPY. , 1964, The Journal of surgical research.

[115]  S. Rose,et al.  A continuous long-term injector. , 1955, The Australian journal of experimental biology and medical science.

[116]  S. de Jongh,et al.  The influence of divided doses of drugs on the duration of effect and integral of effect. , 1950, Acta physiologica et pharmacologica Neerlandica.

[117]  A. G. V. van GEMERT,et al.  Optimal dosage of drugs. , 1950, Acta physiologica et pharmacologica Neerlandica.

[118]  U. G. Dailey Cancer,Facts and Figures about. , 2022, Journal of the National Medical Association.