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Drug Delivery: Localized and Systemic Therapeutic Strategies with Polymer Systems

  • Scott CampbellEmail author
  • Niels Smeets
Living reference work entry
Part of the Polymers and Polymeric Composites: A Reference Series book series (POPOC)

Abstract

This chapter expands upon some of the basic concepts regarding drug delivery and takes a tour through various regions of the body that are commonly treated locally with controlled release systems, investigating current research and commercial strategies involving the use of polymeric systems within each region after briefly describing the biology and the typical biological targets of each region. This section includes drug delivery throughout the gastrointestinal tract and to the skin, lungs, brain, and eye, along with several others. The use of polymeric materials for systemic controlled release is then briefly described and thoroughly investigated in a case study on the most common target of systemically delivered nanomedicines: cancer. The chapter concludes with a perspective on where the field of drug delivery is headed in the future.

List of Abbreviations

AMD

Age-related macular degeneration

AMF

Alternating magnetic field

AMT

Adsorptive-mediated transcytosis

APC

Antigen-presenting cells

BA

Bioavailability

BBB

Blood-brain barrier

BCNU

1,3-bis(2-Chloroethyl)-1-nitrosourea

BRB

Blood-retinal barrier

CNS

Central nervous system

COPD

Chronic obstructive pulmonary disease

CPT

Camptothecin

DNA

Deoxyribonucleic acid

Dox

Doxorubicin

DSPE

Distearoylphosphatidylethanolamine

EGF

Epidermal growth factor

EPR

Enhanced permeability and retention

EVA

Ethylene vinyl acetate

F(ab′)2

Dimers of Fabs

Fab

Antigen-binding fragments

FDA

U.S. Food and Drug Administration

FGF

Fibroblast growth factor

GI

Gastrointestinal

GM-CSF

Granulocyte-macrophage colony-stimulating factor

HA

Hyaluronic acid

HGH

Human growth hormone

HIV

Human immunodeficiency virus

HPV

Human papillomavirus

IGF-1

Insulin-like growth factor

IgG

Immunoglobulin G

IR

Infrared

LbL

Layer-by-layer

LCST

Lower critical solution temperature

LRP

Low-density lipoprotein receptor-related protein

MPEG

Methyl ether poly(ethylene glycol)

MPS

Mononuclear phagocyte system

MRI

Magnetic resonance imaging

NCS

Nanotoxicological classification system

NIPAM

N-Isopropyl acrylamide

PAMAM

Polyamidoamine

PBA

Phenyl boronic acid

PBAE

Poly(β-amino ester)

PCL

Polycaprolactone

PDGF

Platelet-derived growth factor

PDMS

Polydimethylsiloxane

PEG

Poly(ethylene glycol)

PEI

Poly(ethylene imine)

PEM

Polyelectrolyte multilayers

PEO

Poly(ethylene oxide)

PHEMA

Poly(2-hydroxyethyl methacrylate)

PLGA

Poly(lactic acid-co-glycolic acid)

PMMA

poly(methyl methacrylate)

PNIPAM

Poly(N-isopropyl acrylamide)

POEGMA

Poly(oligoethylene glycol methacrylate)

PPO

Poly(propylene oxide)

Ptx

Paclitaxel

PVA

Polyvinyl alcohol

RGD

Arginine-glycine-aspartic acid

RNA

Ribonucleic acid

SC

Subcutaneous

scFv

Single-chain fragment variables

siRNA

Small-interfering RNA

SPIONs

Superparamagnetic iron oxide nanoparticles

Tg

Glass transition temperature

TGF-β1

Transforming growth factor

UV

Ultraviolet

VPPT

Volume phase transition temperature

References

  1. 1.
    N. Huebsch, C.J. Kearney, X. Zhao, J. Kim, C.A. Cezar, Z. Suo, D.J. Mooney, Ultrasound-triggered disruption and self-healing of reversibly cross-linked hydrogels for drug delivery and enhanced chemotherapy. Proc. Natl. Acad. Sci. U. S. A. 111, 9762–9767 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    D. Maitland, S.B. Campbell, J. Chen, T. Hoare, Controlling the resolution and duration of pulsatile release from injectable magnetic “plum pudding” nanocomposite hydrogels. RSC Adv. 6, 15770–15781 (2016)CrossRefGoogle Scholar
  3. 3.
    S.V. Sastry, J.R. Nyshadham, J.A. Fix, Recent technological advances in oral drug delivery – a review. Pharm. Sci. Technol. Today 3, 138–145 (2000)PubMedCrossRefGoogle Scholar
  4. 4.
    L.M. Ensign, R. Cone, J. Hanes, Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers. Adv. Drug Deliv. Rev. 64, 557–570 (2012)PubMedCrossRefGoogle Scholar
  5. 5.
    E.M. Pridgen, F. Alexis, O.C. Farokhzad, Polymeric nanoparticle technologies for oral drug delivery challenges of oral delivery. Clin. Gastroenterol. Hepatol. 12, 1605–1610 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    R. Langer, Drug delivery and targeting. Nature 392, 5–10 (1998)PubMedGoogle Scholar
  7. 7.
    K. Sonaje, K. Lin, S. Wey, C. Lin, T. Yeh, H. Nguyen, C. Hsu, T. Yen, J. Juang, H. Sung, Biodistribution, pharmacodynamics and pharmacokinetics of insulin analogues in a rat model: oral delivery using pH-responsive nanoparticles vs. subcutaneous injection. Biomaterials 31, 6849–6858 (2010)PubMedCrossRefGoogle Scholar
  8. 8.
    Q. Xu, L.M. Ensign, N.J. Boylan, A. Schon, X. Gong, J.-C. Yang, N.W. Lamb, S. Cai, T. Yu, E. Freire, J. Hanes, Impact of surface polyethylene glycol (PEG) density on biodegradable nanoparticle transport in mucus ex vivo and distribution in vivo. ACS Nano 9, 9217–9227 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    K.Y. Win, S. Feng, Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. Biomaterials 26, 2713–2722 (2005)PubMedCrossRefGoogle Scholar
  10. 10.
    E. Cochran, C. Musso, P. Gorden, The use of U-500 in patients with extreme insulin resistance. Diabetes Care 28, 1240–1244 (2005)PubMedCrossRefGoogle Scholar
  11. 11.
    M. Chen, K. Sonaje, K. Chen, H. Sung, A review of the prospects for polymeric nanoparticle platforms in oral insulin delivery. Biomaterials 32, 9826–9838 (2011)PubMedCrossRefGoogle Scholar
  12. 12.
    L.T. Kuhn, Biomaterials, in Introduction to Biomedical Engineering, 4th edn., ed. by J. Enderle, S. Blanchard, J. Bronzino (Elsevier Academic, Burlington, 2005)Google Scholar
  13. 13.
    N.A. Peppas, P. Bures, W. Leobandung, H. Ichikawa, Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm. 50, 27–46 (2000)PubMedCrossRefGoogle Scholar
  14. 14.
    Y. Kim, J. Park, M.R. Prausnitz, Microneedles for drug and vaccine delivery. Adv. Drug Deliv. Rev. 64, 1547–1568 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    M.R. Prausnitz, R. Langer, Transdermal drug delivery. Nat. Biotechnol. 26, 1261–1268 (2008)PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    N.R. Mathias, M.A. Hussain, Non-invasive systemic drug delivery: developability considerations for alternate routes of administration. J. Pharm. Sci. 99, 1–20 (2010)PubMedCrossRefGoogle Scholar
  17. 17.
    J.J. Norman, J.M. Arya, M.A. McClain, P.M. Frew, M.I. Meltzer, M.R. Prausnitz, Microneedle patches: usability and acceptability for self-vaccination against influenza. Vaccine 32, 1856–1862 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    E.M. Saurer, R.M. Flessner, S.P. Sullivan, M.R. Prausnitz, D.M. Lynn, Layer-by-layer assembly of DNA- and protein-containing films on microneedles for drug delivery to the skin. Biomacromolecules 11, 3136–3143 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    B.P.C. Demuth, X. Su, R.E. Samuel, P.T. Hammond, D.J. Irvine, Nano-layered microneedles for transcutaneous delivery of polymer nanoparticles and plasmid DNA. Adv. Mater. 22, 4851–4856 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    M. Kim, B. Jung, J. Park, Hydrogel swelling as a trigger to release biodegradable polymer microneedles in skin. Biomaterials 33, 668–678 (2012)PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    G. Wiedermann, Patient compliance in the use of Vivotif Berna vaccine, typhoid vaccine, live oral Ty21a. J. Travel Med. 5, 1–2 (1998)PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    J.S. Boateng, K.H. Matthews, H.N.E. Stevens, G.M. Eccleston, Wound healing dressings and drug delivery systems: a review. J. Pharm. Sci. 97, 2892–2923 (2008)PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    H. Ueno, T. Mori, T. Fujinaga, Topical formulations and wound healing applications of chitosan. Adv. Drug Deliv. Rev. 52, 105–115 (2001)PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Y. Sawadal, M. Ara, T. Yotsuyanagi, K. Sonet, Treatment of dermal depth burn wounds with an antimicrobial agent-releasing silicone gel sheet. Burns 16, 347–352 (1990)CrossRefGoogle Scholar
  25. 25.
    A.C. Lee, H. Leem, J. Lee, K. Chan, Reversal of silver sulfadiazine-impaired wound healing by epidermal growth factor. Biomaterials 26, 4670–4676 (2005)PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    S. Park, J. Koo, H. Suh, Evaluation of antibiotic-loaded collagen-hyaluronic acid matrix as a skin substitute. Biomaterials 25, 3689–3698 (2004)PubMedCrossRefGoogle Scholar
  27. 27.
    H. Storrie, D.J. Mooney, Sustained delivery of plasmid DNA from polymeric scaffolds for tissue engineering. Adv. Drug Deliv. Rev. 58, 500–514 (2006)PubMedCrossRefGoogle Scholar
  28. 28.
    M.M. Bailey, C.J. Berkland, Nanoparticle formulations in pulmonary drug delivery. Med. Res. Rev. 29, 196–212 (2008)CrossRefGoogle Scholar
  29. 29.
    J.S. Patil, S. Sarasija, Pulmonary drug delivery strategies: a concise, systematic review. Lung India 29, 44–49 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    D.A. Edwards, J. Hanes, G. Caponetti, J. Hrkach, A. Ben-Jebria, M. Lou Eskew, J. Mintzes, D. Deaver, N. Lotan, R. Langer, Large porous particles for pulmonary drug delivery. Science 276, 1868–1871 (1997)PubMedCrossRefGoogle Scholar
  31. 31.
    E. Rytting, J. Nguyen, X. Wang, T. Kissel, Biodegradable polymeric nanocarriers for pulmonary drug delivery. Expert Opin. Drug Deliv. 5, 629–639 (2008)PubMedCrossRefGoogle Scholar
  32. 32.
    M. Beck-Broichsitter, O.M. Merkel, T. Kissel, Controlled pulmonary drug and gene delivery using polymeric nano-carriers. J. Control. Release 161, 214–224 (2012)PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    F. Ungaro, I. Angelo, A. Miro, M.I. La Rotonda, F. Quaglia, Engineered PLGA nano- and micro-carriers for pulmonary delivery: challenges and promises. J. Pharm. Pharmacol. 64, 1217–1235 (2012)PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    M. Paranjpe, C.C. Müller-Goymann, Nanoparticle-mediated pulmonary drug delivery: a review. Int. J. Mol. Sci. 15, 5852–5873 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    J.S. Patton, C.S. Fishburn, J.G. Weers, The lungs as a portal of entry for systemic drug delivery. Proc. Am. Thorac. Soc. 1, 338–344 (2004)PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    J.C. Sung, D.J. Padilla, L. Garcia-Contreras, J.L. Verberkmoes, D. Durbin, C.A. Peloquin, K.J. Elbert, A.J. Hickey, D.A. Edwards, Formulation and pharmacokinetics of self-assembled rifampicin nanoparticle systems for pulmonary delivery. Pharm. Res. 26, 1847–1855 (2009)PubMedCrossRefGoogle Scholar
  37. 37.
    M. Dutt, G.K. Khuller, Chemotherapy of Mycobacterium tuberculosis infections in mice with a combination of isoniazid and rifampicin entrapped in poly(dl-lactide-co-glycolide) microparticles. J. Antimicrob. Chemother. 47, 829–835 (2001)PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    M. Dutt, G.K. Khuller, Sustained release of isoniazid from a single injectable dose of poly(dl-lactide-co-glycolide) microparticles as a therapeutic approach towards tuberculosis. Int. J. Antimicrob. Agents 17, 115–122 (2001)PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    I.M. El-Sherbiny, S. McGill, H.D.C. Smyth, Swellable microparticles as carriers for sustained pulmonary drug delivery. J. Pharm. Sci. 99, 2343–2356 (2010)PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    E. Kleemann, M. Neu, N. Jekel, L. Fink, T. Schmehl, T. Gessler, W. Seeger, T. Kissel, Nano-carriers for DNA delivery to the lung based upon a TAT-derived peptide covalently coupled to PEG–PEI. J. Control. Release 109, 299–316 (2005)PubMedCrossRefGoogle Scholar
  41. 41.
    J. Nguyen, T.W.J. Steele, O. Merkel, R. Reul, T. Kissel, Fast degrading polyesters as siRNA nano-carriers for pulmonary gene therapy. J. Control. Release 132, 243–251 (2008)PubMedCrossRefGoogle Scholar
  42. 42.
    W. Zhang, H. Yang, X. Kong, S. Mohapatra, H.S. Juan-Vergara, G. Hellermann, S. Behera, R. Singam, R.F. Lockey, S.S. Mohapatra, Inhibition of respiratory syncytial virus infection with intranasal siRNA nanoparticles targeting the viral NS1 gene. Nat. Med. 11, 56–62 (2005)PubMedCrossRefGoogle Scholar
  43. 43.
    X. Kong, W. Zhang, R.F. Lockey, A. Auais, G. Piedimonte, S.S. Mohapatra, Respiratory syncytial virus infection in Fischer 344 rats is attenuated by short interfering RNA against the RSV-NS1 gene. Genet. Vaccines Ther. 5, 1–8 (2007)CrossRefGoogle Scholar
  44. 44.
    H. Yamamoto, Y. Kuno, S. Sugimoto, H. Takeuchi, Y. Kawashima, Surface-modified PLGA nanosphere with chitosan improved pulmonary delivery of calcitonin by mucoadhesion and opening of the intercellular tight junctions. J. Control. Release 102, 373–381 (2005)PubMedCrossRefGoogle Scholar
  45. 45.
    K.K. Gill, S. Nazzal, A. Kaddoumi, Paclitaxel loaded PEG5000–DSPE micelles as pulmonary delivery platform: formulation characterization, tissue distribution, plasma pharmacokinetics, and toxicological evaluation. Eur. J. Pharm. Biopharm. 79, 276–284 (2011)PubMedCrossRefGoogle Scholar
  46. 46.
    S. Wohlfart, S. Gelperina, J. Kreuter, Transport of drugs across the blood – brain barrier by nanoparticles. J. Control. Release 161, 264–273 (2012)PubMedCrossRefGoogle Scholar
  47. 47.
    P.R. Lockman, R.J. Mumper, M.A. Khan, D.D. Allen, Nanoparticle technology for drug delivery across the blood-brain barrier. Drug Dev. Ind. Pharm. 28, 1–13 (2002)PubMedCrossRefGoogle Scholar
  48. 48.
    M. Elsabahy, K.L. Wooley, Design of polymeric nanoparticles for biomedical delivery applications. Chem. Soc. Rev. 41, 2545–2561 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    H.-L. Liu, M.-Y. Hua, P.-Y. Chen, P.-C. Chu, C.-H. Pan, H.-W. Yang, C.-Y. Huang, J.-J. Wang, T.-C. Yen, K.-C. Wei, Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment. Radiology 255, 415–425 (2010)PubMedCrossRefGoogle Scholar
  50. 50.
    J. Nicolas, S. Mura, D. Brambilla, N. Mackiewicz, P. Couvreur, Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery. Chem. Soc. Rev. 42, 1147–1235 (2013)PubMedCrossRefGoogle Scholar
  51. 51.
    Z. Pang, L. Feng, R. Hua, J. Chen, H. Gao, S. Pan, X. Jiang, P. Zhang, Lactoferrin-conjugated biodegradable polymersomes holding doxorubicin and tetrandrine for chemotherapy of glioma rats. Mol. Pharm. 7, 1995–2005 (2010)PubMedCrossRefGoogle Scholar
  52. 52.
    Z. Pang, H. Gao, Y. Yu, L. Guo, J. Chen, S. Pan, J. Ren, Z. Wen, X. Jiang, Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin. Bioconjug. Chem. 22, 1171–1180 (2011)PubMedCrossRefGoogle Scholar
  53. 53.
    H. Gao, J. Qian, S. Cao, Z. Yang, Z. Pang, S. Pan, L. Fan, Z. Xi, X. Jiang, Precise glioma targeting of and penetration by aptamer and peptide dual-functioned nanoparticles. Biomaterials 33, 5115–5123 (2012)PubMedCrossRefGoogle Scholar
  54. 54.
    U. Bickel, T. Yoshikawa, W.M. Pardridge, Delivery of peptides and proteins through the blood–brain barrier. Adv. Drug Deliv. Rev. 46, 247–279 (2001)PubMedCrossRefGoogle Scholar
  55. 55.
    L. Illum, Nasal drug delivery – possibilities, problems and solutions. J. Control. Release 87, 187–198 (2003)PubMedCrossRefGoogle Scholar
  56. 56.
    J. Piazza, T. Hoare, L. Molinaro, K. Terpstra, J. Bhandari, P.R. Selvaganapathy, B. Gupta, R.K. Mishra, Haloperidol-loaded intranasally administered lectin functionalized poly(ethylene glycol)–block-poly (d,l)-lactic-co-glycolic acid (PEG-PLGA) nanoparticles for the treatment of schizophrenia. Eur. J. Pharm. Biopharm. 87, 30–39 (2014)PubMedCrossRefGoogle Scholar
  57. 57.
    F.J. Attenello, D. Mukherjee, G. Datoo, M.J. McGirt, E. Bohan, J.D. Weingart, A. Olivi, A. Quinones-Hinojosa, H. Brem, Use of Gliadel (BCNU) wafer in the surgical treatment of malignant glioma: a 10-year institutional experience. Ann. Surg. Oncol. 15, 2887–2893 (2008)PubMedCrossRefGoogle Scholar
  58. 58.
    H. Brem, S. Piantadosi, P.C. Burger, M. Walker, R. Selker, N.A. Vick, K. Black, M. Sisti, S. Brem, G. Mohr, P. Muller, R. Morawetz, S.C. Schold, Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345, 1008–1012 (1995)PubMedCrossRefGoogle Scholar
  59. 59.
    S. Kunwar, S. Chang, M. Westphal, M. Vogelbaum, J. Sampson, G. Barnett, M. Shaffrey, Z. Ram, J. Piepmeier, M. Prados, D. Croteau, C. Pedain, P. Leland, S.R. Husain, B.H. Joshi, R.K. Puri, Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma. Neuro Oncol. 12, 871–881 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    G.Y. Kim, B.M. Tyler, M.M. Tupper, J.M. Karp, R.S. Langer, H. Brem, M.J. Cima, Resorbable polymer microchips releasing BCNU inhibit tumor growth in the rat 9L flank model. J. Control. Release 123, 172–178 (2007)PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    U.B. Kompella, A.C. Amrite, R. Pacha, S.A. Durazo, Nanomedicines for back of the eye drug delivery, gene delivery, and imaging. Prog. Retin. Eye Res. 36, 172–198 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    M.E. Myles, D.M. Neumann, J.M. Hill, Recent progress in ocular drug delivery for posterior segment disease: emphasis on transscleral iontophoresis. Adv. Drug Deliv. Rev. 57, 2063–2079 (2005)PubMedCrossRefGoogle Scholar
  63. 63.
    M.N. Yasin, D. Svirskis, A. Seyfoddin, I.D. Rupenthal, Implants for drug delivery to the posterior segment of the eye: a focus on stimuli-responsive and tunable release systems. J. Control. Release 196, 208–221 (2014)PubMedCrossRefGoogle Scholar
  64. 64.
    Y. Chun, B. Chiang, X. Wu, M.R. Prausnitz, Ocular delivery of macromolecules. J. Control. Release 190, 172–181 (2014)CrossRefGoogle Scholar
  65. 65.
    E. Lavik, M.H. Kuehn, Y.H. Kwon, Novel drug delivery systems for glaucoma. Eye 25, 578–586 (2011)PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    N. Kuno, S. Fujii, Recent advances in ocular drug delivery systems. Polymers 3, 193–221 (2011)CrossRefGoogle Scholar
  67. 67.
    N. Nagai, H. Kaji, H. Onami, Y. Ishikawa, M. Nishizawa, A polymeric device for controlled transscleral multi-drug delivery to the posterior segment of the eye. Acta Biomater. 10, 680–687 (2014)PubMedCrossRefGoogle Scholar
  68. 68.
    M. Allansmith, A. De Ramus, D. Maurice, The dynamics of IgG in the cornea. Invest. Ophthalmol. Vis. Sci. 18, 947–955 (1979)PubMedGoogle Scholar
  69. 69.
    H. Sheardown, Critical role for drug delivery in the development of new ophthalmic treatments. Future Med. Chem. 4, 2123–2125 (2012)PubMedCrossRefGoogle Scholar
  70. 70.
    S.D. Fitzpatrick, M.A. Jafar Mazumder, F. Lasowski, L.E. Fitzpatrick, H. Sheardown, PNIPAAm-grafted-collagen as an injectable, in situ gelling, bioactive cell delivery scaffold. Biomacromolecules 11, 2261–2267 (2010)PubMedCrossRefGoogle Scholar
  71. 71.
    V. Delplace, S. Payne, M. Shoichet, Delivery strategies for treatment of age-related ocular diseases: from a biological understanding to biomaterial solutions. J. Control. Release 219, 652–668 (2015)PubMedCrossRefGoogle Scholar
  72. 72.
    T.R. Thrimawithana, S. Young, C.R. Bunt, C. Green, R.G. Alany, Drug delivery to the posterior segment of the eye. Drug Discov. Today 16, 270–277 (2011)PubMedCrossRefGoogle Scholar
  73. 73.
    F.M. Veronese, A. Mero, The impact of PEGylation on biological therapies. BioDrugs 22, 315–329 (2008)PubMedCrossRefGoogle Scholar
  74. 74.
    J. Jiang, J.S. Moore, H.F. Edelhauser, M.R. Prausnitz, Intrascleral drug delivery to the eye using hollow microneedles. Pharm. Res. 26, 399–403 (2009)CrossRefGoogle Scholar
  75. 75.
    S.R. Patel, A.S. Lin, H.F. Edelhauser, M.R. Prausnitz, Suprachoroidal drug delivery to the back of the eye using hollow microneedles. Pharm. Res. 28, 166–176 (2011)PubMedCrossRefGoogle Scholar
  76. 76.
    A.L. Gomes dos Santos, A. Bochot, A. Doyle, N. Tsapis, J. Siepmann, F. Siepmann, J. Schmaler, M. Besnard, F. Behar-Cohen, E. Fattal, Sustained release of nanosized complexes of polyethylenimine and anti-TGF-β2 oligonucleotide improves the outcome of glaucoma surgery. J. Control. Release 112, 369–381 (2006)PubMedCrossRefGoogle Scholar
  77. 77.
    T. Hoare, S.B. Campbell, W.-I. Wu, J. Yang, P.R. Selvaganapathy, A microinjection device for delivering in situ-gelling hydrogels for posterior segment drug delivery. Invest. Ophthalmol. Vis. Sci. 55, 478 (2014)Google Scholar
  78. 78.
    M. Patenaude, N.M.B. Smeets, T. Hoare, Designing injectable, covalently cross-linked hydrogels for biomedical applications. Macromol. Rapid Commun. 35(6), 1–20 (2014)PubMedCrossRefGoogle Scholar
  79. 79.
    G. Zhu, Y. Zhang, K. Wang, X. Zhao, H. Lian, H. Wang, J. Wu, Y. Hu, H. Guo, G. Zhu, Y. Zhang, K. Wang, X. Zhao, H. Lian, G. Zhu, Y. Zhang, K. Wang, X. Zhao, H. Lian, W. Wang, H. Wang, Visualized intravesical floating hydrogel encapsulating vaporized perfluoropentane for controlled drug release. Drug Deliv. 23, 2820–2826 (2016)PubMedCrossRefGoogle Scholar
  80. 80.
    D. Zhang, P. Sun, P. Li, A. Xue, X. Zhang, H. Zhang, X. Jin, A magnetic chitosan hydrogel for sustained and prolonged delivery of Bacillus Calmette-Guérin in the treatment of bladder cancer. Biomaterials 34, 10258–10266 (2013)PubMedCrossRefGoogle Scholar
  81. 81.
    Y.L. Traore, Y. Chen, A. Bernier, A. Ho, Impact of hydroxychloroquine-loaded polyurethane intravaginal rings on Lactobacilli. Antimicrob. Agents Chemother. 59, 7680–7686 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    E.A. Ho, Intravaginal rings as a novel platform for mucosal vaccination. Mol. Pharm. Org. Process Res. 1, 1–2 (2013)Google Scholar
  83. 83.
    S. Kim, Y. Chen, E.A. Ho, S. Liu, Reversibly pH-responsive polyurethane membranes for on-demand intravaginal drug delivery. Acta Biomater. 47, 100–112 (2017)PubMedCrossRefGoogle Scholar
  84. 84.
    S. Yang, Y. Chen, R. Ahmadie, E.A. Ho, Advancements in the field of intravaginal siRNA delivery. J. Control. Release 167, 29–39 (2013)PubMedCrossRefGoogle Scholar
  85. 85.
    W.C. Carlyle, J.B. McClain, A.R. Tzafriri, L. Bailey, G. Brett, P.M. Markham, J.R.L. Stanley, E.R. Edelman, Enhanced drug delivery capabilities from stents coated with absorbable polymer and crystalline drug. J. Control. Release 162, 561–567 (2015)CrossRefGoogle Scholar
  86. 86.
    L. Lei, S. Guo, W. Chen, H. Rong, F. Lu, Stents as a platform for drug delivery. Expert Opin. Drug Deliv. 8, 813–831 (2011)PubMedCrossRefGoogle Scholar
  87. 87.
    T. Keler, V. Ramakrishna, M. Fanger, Mannose receptor-targeted vaccines. Expert Opin. Biol. Ther. 4, 1953–1962 (2004)PubMedCrossRefGoogle Scholar
  88. 88.
    T. Sun, Y.S. Zhang, B. Pang, D.C. Hyun, M. Yang, Y. Xia, Engineered nanoparticles for drug delivery in cancer therapy. Angew. Chem. Int. Ed. 53, 12320–12364 (2014)Google Scholar
  89. 89.
    D. Hanahan, R.A. Weinberg, The hallmarks of cancer. Cell 100, 57–70 (2000)CrossRefGoogle Scholar
  90. 90.
    D. Peer, J.M. Karp, S. Hong, O.C. Farokhzad, R. Margalit, R. Langer, Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2, 751–760 (2007)PubMedCrossRefGoogle Scholar
  91. 91.
    R. Tong, D.S. Kohane, New strategies in cancer nanomedicine. Annu. Rev. Pharmacol. Toxicol. 56, 41–57 (2016)PubMedCrossRefGoogle Scholar
  92. 92.
    T.M. Allen, P.R. Cullis, Drug delivery systems: entering the mainstream. Science 303, 1818–1822 (2003)CrossRefGoogle Scholar
  93. 93.
    Y.H. Bae, K. Park, Targeted drug delivery to tumors: myths, reality and possibility. J. Control. Release 153, 198–205 (2012)CrossRefGoogle Scholar
  94. 94.
    A.A. Gabizon, Stealth liposomes and tumor targeting: one step further in the quest for the magic bullet. Clin. Cancer Res. 7, 223–225 (2001)PubMedGoogle Scholar
  95. 95.
    A.K. Iyer, G. Khaled, J. Fang, H. Maeda, Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov. Today 11, 812–818 (2006)PubMedCrossRefGoogle Scholar
  96. 96.
    G. Bergers, L.E. Benjamin, Tumorigenesis and the angiogenic switch. Nat. Rev. Cancer 3, 401–410 (2003)PubMedCrossRefGoogle Scholar
  97. 97.
    B. Haley, E. Frenkel, Nanoparticles for drug delivery in cancer treatment. Urol. Oncol. 26, 57–64 (2008)PubMedCrossRefGoogle Scholar
  98. 98.
    Y. Matsumura, H. Maeda, A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46, 6387–6392 (1986)PubMedGoogle Scholar
  99. 99.
    M.J. Alonso, Nanomedicines for overcoming biological barriers. Biomed. Pharmacother. 58, 168–172 (2004)PubMedCrossRefGoogle Scholar
  100. 100.
    R.K. Jain, T. Stylianopoulos, Delivering nanomedicine to solid tumors. Nat. Rev. Clin. Oncol. 7, 653–664 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    P. Decuzzi, S. Lee, B. Bhushan, M. Ferrari, A theoretical model for the margination of particles within blood vessels. Ann. Biomed. Eng. 33, 179–190 (2005)PubMedCrossRefGoogle Scholar
  102. 102.
    P. Decuzzi, R. Pasqualini, W. Arap, M. Ferrari, Intravascular delivery of particulate systems: does geometry really matter? Pharm. Res. 26, 235–243 (2009)PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    V.P. Torchilin, Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov. 4, 145–160 (2005)PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    H.M. Warenius, G. Galfre, N.M. Bleehen, C. Milstein, Attempted targeting of a monoclonal antibody in a human tumour xenograft system. Eur. J. Cancer Clin. Oncol. 17, 1009–1015 (1981)PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    D.E.L. De Menezes, L.M. Pilarski, T.M. Allen, In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-cell lymphoma. Cancer Res. 58, 3320–3331 (2000)Google Scholar
  106. 106.
    J.W. Park, K. Hong, D.B. Kirpotin, G. Colbern, R. Shalaby, J. Baselga, Y. Shao, U.B. Nielsen, J.D. Marks, D. Moore, D. Papahadjopoulos, C.C. Benz, Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery. Clin. Cancer Res. 8, 1172–1181 (2002)PubMedGoogle Scholar
  107. 107.
    J. Majoros, B.G. Orr, J.R. Baker, S. Hong, P.R. Leroueil, M.M.B. Holl, The binding avidity of a nanoparticle-based multivalent targeted drug delivery platform. Chem. Biol. 14, 107–115 (2007)PubMedCrossRefGoogle Scholar
  108. 108.
    D. Peer, P. Zhu, C.V. Carmen, J. Lieberman, M. Shimaoka, Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1. Proc. Natl. Acad. Sci. U. S. A. 104, 4095–4100 (2007)PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    O.C. Farokhzad, J. Cheng, B.A. Teply, I. Sherifi, S. Jon, P. Kantoff, J.P. Richie, R. Langer, Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc. Natl. Acad. Sci. U. S. A. 103, 6315–6320 (2006)PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Y.N. Dou, J. Zheng, W.D. Foltz, R. Weersink, N. Chaudary, D.A. Jaffray, C. Allen, Heat-activated thermosensitive liposomal cisplatin (HTLC) results in effective growth delay of cervical carcinoma in mice. J. Control. Release 178, 69–78 (2014)PubMedCrossRefGoogle Scholar
  111. 111.
    S. Heilmann, S. Küchler, C. Wischke, A. Lendlein, C. Stein, M. Schäfer-Korting, A thermosensitive morphine-containing hydrogel for the treatment of large-scale skin wounds. Int. J. Pharm. 444, 96–102 (2013)PubMedCrossRefGoogle Scholar
  112. 112.
    R. Pelton, Temperature-sensitive aqueous microgels. Adv. Colloid Interface Sci. 85, 1–33 (2000)PubMedCrossRefGoogle Scholar
  113. 113.
    C. Ju, R. Mo, J. Xue, L. Zhang, Z. Zhao, L. Xue, Q. Ping, C. Zhang, Sequential intra-intercellular nanoparticle delivery system for deep tumor penetration. Angew. Chem. Int. Ed. 53, 6253–6258 (2014)CrossRefGoogle Scholar
  114. 114.
    C.L. Lay, J.N. Kumar, C.K. Liu, X. Lu, Y. Liu, A rocket-like encapsulation and delivery system with two-stage booster layers: pH-responsive poly(methacrylic acid)/poly(ethylene glycol) complex-coated hollow silica vesicles. Macromol. Rapid Commun. 34, 1563–1568 (2013)PubMedCrossRefGoogle Scholar
  115. 115.
    X. Yao, L. Chen, X. Chen, C. He, J. Zhang, X. Chen, Metallo-supramolecular nanogels for intracellular pH-responsive drug release. Macromol. Rapid Commun. 35, 1697–1705 (2014)PubMedCrossRefGoogle Scholar
  116. 116.
    T. Hoare, R. Pelton, Charge-switching, amphoteric glucose-responsive microgels with physiological swelling activity. Biomacromolecules 9, 733–740 (2008)PubMedCrossRefGoogle Scholar
  117. 117.
    A. Matsumoto, K. Yamamoto, R. Yoshida, K. Kataoka, T. Aoyagi, Y. Miyahara, A totally synthetic glucose responsive gel operating in physiological aqueous conditions. Chem. Commun. 46, 2203–2205 (2010)CrossRefGoogle Scholar
  118. 118.
    S. Mura, J. Nicolas, P. Couvreur, Stimuli-responsive nanocarriers for drug delivery. Nat. Mater. 12, 991–1003 (2013)PubMedCrossRefGoogle Scholar
  119. 119.
    S. Merino, C. Martin, K. Kostarelos, M. Prato, E. Vazquez, Nanocomposite hydrogels: 3D polymer-nanoparticle synergies for on-demand drug delivery. ACS Nano 9, 4686–4697 (2015)PubMedCrossRefGoogle Scholar
  120. 120.
    S. Laurent, D. Forge, M. Port, A. Roch, C. Robic, L. Vander Elst, R.N. Muller, Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem. Rev. 108, 2064–2110 (2008)PubMedCrossRefGoogle Scholar
  121. 121.
    M. Sepantafar, R. Maheronnaghsh, H. Mohammadi, F. Radmanesh, M.M. Hasani-Sadrabadi, M. Ebrahimi, Engineered hydrogels in cancer therapy and diagnosis. Trends Biotechnol. 35, 1074–1087 (2017)PubMedCrossRefGoogle Scholar
  122. 122.
    T. Tagami, W.D. Foltz, M.J. Ernsting, C.M. Lee, I.F. Tannock, J.P. May, S. Li, MRI monitoring of intratumoral drug delivery and prediction of the therapeutic effect with a multifunctional thermosensitive liposome. Biomaterials 32, 6570–6578 (2011)PubMedCrossRefGoogle Scholar
  123. 123.
    S. Lee, H. Park, J. Choi, Y.N. Park, C. Yun, H. Yoo, Multifunctional nanoparticles for targeted chemophotothermal treatment of cancer cells. Angew. Chem. Int. Ed. 50, 7581–7586 (2011)CrossRefGoogle Scholar
  124. 124.
    P. Wust, B. Hildebrandt, G. Sreenivasa, B. Rau, J. Gellermann, H. Riess, R. Felix, P.M. Schlag, Review. Hyperthermia in combined treatment of cancer. Lancet Oncol. 3, 487–497 (2002)PubMedCrossRefGoogle Scholar
  125. 125.
    I. Hilger, W.A. Kaiser, Iron oxide-based nanostructures for MRI and magnetic hyperthermia. Nanomedicine 7, 1443–1459 (2012)PubMedCrossRefGoogle Scholar
  126. 126.
    P. Pradhan, J. Giri, F. Rieken, C. Koch, O. Mykhaylyk, M. Döblinger, R. Banerjee, D. Bahadur, C. Plank, Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy. J. Control. Release 142, 108–121 (2010)PubMedCrossRefGoogle Scholar
  127. 127.
    B. Thiesen, A. Jordan, Clinical applications of magnetic nanoparticles for hyperthermia. Int. J. Hyperthermia 24, 467–474 (2008)PubMedCrossRefGoogle Scholar
  128. 128.
    J. Gautier, E. Allard-Vannier, E. Munnier, M. Soucé, I. Chourpa, Recent advances in theranostic nanocarriers of doxorubicin based on iron oxide and gold nanoparticles. J. Control. Release 169, 48–61 (2013)PubMedCrossRefGoogle Scholar
  129. 129.
    C.S. Brazel, Magnetothermally-responsive nanomaterials: combining magnetic nanostructures and thermally-sensitive polymers for triggered drug release. Pharm. Res. 26, 644–656 (2009)PubMedCrossRefGoogle Scholar
  130. 130.
    S. Hu, S. Chen, X. Gao, Multifunctional nanocapsules for simultaneous encapsulation of hydrophilic and hydrophobic compounds and on-demand release. ACS Nano 6, 2558–2565 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    M. Mahmoudi, S. Sant, B. Wang, S. Laurent, T. Sen, Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy. Adv. Drug Deliv. Rev. 63, 24–46 (2011)PubMedCrossRefGoogle Scholar
  132. 132.
    W.-H. Chiang, V.T. Ho, H.-H. Chen, W.-C. Huang, Y.-F. Huang, S.-C. Lin, C.-S. Chern, H.-C. Chiu, Superparamagnetic hollow hybrid nanogels as a potential guidable vehicle system of stimuli-mediated MR imaging and multiple cancer therapeutics. Langmuir 29, 6434–6443 (2013)PubMedCrossRefGoogle Scholar
  133. 133.
    Z. Deng, Z. Zhen, X. Hu, S. Wu, Z. Xu, P.K. Chu, Hollow chitosan-silica nanospheres as pH-sensitive targeted delivery carriers in breast cancer therapy. Biomaterials 32, 4976–4986 (2011)PubMedCrossRefGoogle Scholar
  134. 134.
    K. Hyun, J. Kim, S. Mun, H. Shin, M. Sang, S. Park, H. Lee, R. Park, I. Kim, K. Kim, I. Chan, S. Young, D. Sung, Tumoral acidic pH-responsive MPEG-poly(β-amino ester) polymeric micelles for cancer targeting therapy. J. Control. Release 144, 259–266 (2010)CrossRefGoogle Scholar
  135. 135.
    G. Hui Gao, M. Jung Park, Y. Li, G. Ho Im, J. Kim, H. Nyun Kim, J. Won Lee, P. Jeon, O. Young Bang, J. Hee Lee, D. Sung Lee, The use of pH-sensitive positively charged polymeric micelles for protein delivery. Biomaterials 33, 9157–9164 (2012)CrossRefGoogle Scholar
  136. 136.
    W. Wu, T. Zhou, A. Berliner, P. Banerjee, S. Zhou, Smart core−shell hybrid nanogels with Ag nanoparticle core for cancer cell imaging and gel shell for pH-regulated drug delivery. Chem. Mater. 22, 1966–1976 (2010)CrossRefGoogle Scholar
  137. 137.
    M.E.R. O’Brien, N. Wigler, M. Inbar, R. Rosso, E. Grischke, A. Santoro, R. Catane, D.G. Kieback, P. Tomczak, S.P. Ackland, F. Orlandi, L. Mellars, L. Alland, C. Tendler, 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. Ann. Oncol. 15, 440–449 (2004)PubMedCrossRefGoogle Scholar
  138. 138.
    K.S. Lee, H.C. Chung, S.A. Im, Y.H. Park, C.S. Kim, S.-B. Kim, S.Y. Rha, M.Y. Lee, J. Ro, Multicenter phase II trial of Genexol-PM, a Cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer. Breast Cancer Res. Treat. 108, 241–250 (2008)PubMedCrossRefGoogle Scholar
  139. 139.
    P.A. Dinndorf, J. Gootenberg, M.H. Cohen, P. Keegan, R. Pazdur, FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist 12, 991–998 (2007)PubMedCrossRefGoogle Scholar
  140. 140.
    T. Okusaka, S. Okada, H. Ueno, M. Ikeda, R. Iwata, H. Furukawa, K. Takayasu, N. Moriyama, T. Sato, K. Sato, Transcatheter arterial embolization with zinostatin stimalamer for hepatocellular carcinoma. Oncology 62, 228–233 (2002)PubMedCrossRefGoogle Scholar
  141. 141.
    Q. Song, S.D. Merajver, J.Z. Li, Cancer classification in the genomic era: five contemporary problems. Hum. Genomics 9, 1–8 (2015)CrossRefGoogle Scholar
  142. 142.
    L.K. Fung, W.M. Saltzman, Polymeric implants for cancer chemotherapy. Adv. Drug Deliv. Rev. 26, 209–230 (1997)PubMedCrossRefGoogle Scholar
  143. 143.
    P.N. Schlegel, Efficacy and safety of histrelin subdermal implant in patients with advanced prostate cancer. J. Urol. 175, 1353–1358 (2006)PubMedCrossRefGoogle Scholar
  144. 144.
    D.J. Overstreet, D. Dutta, S.E. Stabenfeldt, B.L. Vernon, Injectable hydrogels. J. Polym. Sci. B Polym. Phys. 50, 881–903 (2012)CrossRefGoogle Scholar
  145. 145.
    Y. Li, J. Rodrigues, H. Tomás, Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications. Chem. Soc. Rev. 41, 2193–2221 (2012)PubMedCrossRefGoogle Scholar
  146. 146.
    P. Huang, Y. Zhang, W. Wang, J. Zhou, Y. Sun, J. Liu, D. Kong, J. Liu, A. Dong, Co-delivery of doxorubicin and 131 I by thermosensitive micellar-hydrogel for enhanced in situ synergetic chemoradiotherapy. J. Control. Release 220, 456–464 (2015)PubMedCrossRefGoogle Scholar
  147. 147.
    L. Gu, D.J. Mooney, Biomaterials and emerging anticancer therapeutics: engineering the microenvironment. Nat. Rev. Cancer 16, 56–66 (2016)PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    H. Hu, Z. Lin, B. He, W. Dai, X. Wang, J. Wang, X. Zhang, H. Zhang, Q. Zhang, A novel localized co-delivery system with lapatinib microparticles and paclitaxel nanoparticles in a peritumorally injectable in situ hydrogel. J. Control. Release 220, 189–200 (2015)PubMedCrossRefGoogle Scholar
  149. 149.
    D. Weissglas-Volkov, N. Oliva, E. Friedman, N. Artzi, A. Gilam, N. Shomron, Local microRNA delivery targets Palladin and prevents metastatic breast cancer. Nat. Commun. 7, 12868 (2016)PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    S.B. Campbell, T. Hoare, Externally addressable hydrogel nanocomposites for biomedical applications. Curr. Opin. Chem. Eng. 4, 1–10 (2014)CrossRefGoogle Scholar
  151. 151.
    S.B. Campbell, M. Patenaude, T. Hoare, Injectable superparamagnets: highly elastic and degradable poly(N-isopropylacrylamide)-superparamagnetic iron oxide nanoparticle (SPION) composite hydrogels. Biomacromolecules 14, 644–653 (2013)PubMedCrossRefGoogle Scholar
  152. 152.
    L.E. Strong, S.N. Dahotre, J.L. West, Hydrogel-nanoparticle composites for optically modulated cancer therapeutic delivery. J. Control. Release 178, 63–68 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    B.C. Youan, Chronopharmaceutical drug delivery systems: hurdles, hype or hope? Adv. Drug Deliv. Rev. 62, 898–903 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    R. Tong, H.D. Hemmati, R. Langer, D.S. Kohane, Photoswitchable nanoparticles for triggered tissue penetration and drug delivery. J. Am. Chem. Soc. 134, 8848–8855 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    S. Campbell, D. Maitland, T. Hoare, Enhanced pulsatile drug release from injectable magnetic hydrogels with embedded thermosensitive microgels. ACS Macro Lett. 4, 312–316 (2015)CrossRefGoogle Scholar
  156. 156.
    P.W. Kantoff, C.S. Higano, N.D. Shore, E.R. Berger, E.J. Small, D.F. Penson, C.H. Redfern, A.C. Ferrari, R. Dreicer, R.B. Sims, Y. Xu, D. Ph, M.W. Frohlich, P.F. Schellhammer, Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363, 411–422 (2012)CrossRefGoogle Scholar
  157. 157.
    O. Hamid, C. Robert, A. Daud, F.S. Hodi, W.-J. Hwu, R. Kefford, J.D. Wolchok, P. Hersey, R.W. Joseph, J.S. Weber, R. Dronca, T.C. Gangadhar, A. Patnaik, H. Zarour, A.M. Joshua, K. Gergich, J. Elassaiss-Schaap, A. Algazi, C. Mateus, P. Boasberg, P.C. Tumeh, B. Chmielowski, S.W. Ebbinghaus, X.N. Li, S.P. Kang, A. Ribas, Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 369, 134–144 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    M.A. Postow, J. Chesney, A.C. Pavlick, C. Robert, K. Grossmann, D. McDermott, G.P. Linette, N. Meyer, J.K. Giguere, D. Minor, A.K. Salama, M. Taylor, P.A. Ott, L.M. Rollin, C. Horak, P. Gagnier, J.D. Wolchok, F.S. Hodi, Nivolumab and Ipilimumab versus Ipilimumab in untreated melanoma. N. Engl. J. Med. 372, 2006–2017 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    O.A. Ali, N. Huebsch, L. Cao, G. Dranoff, D.J. Mooney, Infection-mimicking materials to program dendritic cells in situ. Nat. Mater. 8, 151–158 (2009)PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    S.T. Koshy, D.J. Mooney, Biomaterials for enhancing anti-cancer immunity. Curr. Opin. Biotechnol. 40, 1–8 (2016)PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    O.A. Ali, D. Emerich, G. Dranoff, D.J. Mooney, In situ regulation of DC subsets and T cells mediates tumor regression in mice. Sci. Transl. Med. 1, 1–10 (2009)CrossRefGoogle Scholar
  162. 162.
    P. Duewell, U. Kisser, K. Heckelsmiller, S. Hoves, P. Stoitzner, S. Koernig, A.B.. Morelli, B.E. Clausen, M. Dauer, A. Eigler, D. Anz, C. Bourquin, E. Maraskovsky, S. Endres, M. Schnurr, ISCOMATRIX adjuvant combines immune activation with antigen delivery to dendritic cells in vivo leading to effective cross-priming of CD8+ T cells. J. Immunol. 187, 55–63 (2015)CrossRefGoogle Scholar
  163. 163.
    S.A. Bencherif, R.W. Sands, O.A. Ali, W.A. Li, S.A. Lewin, T.M. Braschler, T. Shih, C.S. Verbeke, D. Bhatta, G. Dranoff, D.J. Mooney, Injectable cryogel-based whole-cell cancer vaccines. Nat. Commun. 6, 1–13 (2015)CrossRefGoogle Scholar
  164. 164.
    A.Z. Wang, R. Langer, O.C. Farokhzad, Nanoparticle delivery of cancer drugs. Annu. Rev. Med. 63, 185–198 (2012)PubMedCrossRefGoogle Scholar
  165. 165.
    M.E. Davis, J.E. Zuckerman, C.H.J. Choi, D. Seligson, A. Tolcher, C.A. Alabi, Y. Yen, J.D. Heidel, A. Ribas, Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464, 1067–1070 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    R. Farra, N.F. Sheppard Jr., L. McCabe, R.M. Neer, J.M. Anderson, J.T. Santini Jr., M.J. Cima, R. Langer, First-in-human testing of a wirelessly controlled drug delivery microchip. Sci. Transl. Med. 4, 122ra121 (2012)CrossRefGoogle Scholar
  167. 167.
    J. Li, D.J. Mooney, Designing hydrogels for controlled drug delivery. Nat. Rev. Mater. 1, 1–18 (2016)Google Scholar
  168. 168.
    E. Blanco, H. Shen, M. Ferrari, Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 33, 941–951 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    G. Oberdorster, Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology. J. Intern. Med. 267, 89–105 (2009)CrossRefGoogle Scholar
  170. 170.
    C.M. Keck, R.H. Müller, Nanotoxicological classification system (NCS) – a guide for the risk-benefit assessment of nanoparticulate drug delivery systems. Eur. J. Pharm. Biopharm. 84, 445–448 (2013)PubMedCrossRefGoogle Scholar
  171. 171.
    D. Huh, D.C. Leslie, D. Benjamin, J.P. Fraser, S. Jurek, A. Geraldine, K.S. Thorneloe, M. Allen, D.E. Ingber, A. Human Disease, Model of drug toxicity – induced pulmonary edema in a lung-on-a-chip microdevice. Sci. Transl. Med. 4, 1–8 (2012)CrossRefGoogle Scholar
  172. 172.
    J.A. Doudna, E. Charpentier, The new frontier of genome engineering with CRISPR-Cas9. Science 346, 1258096-1–1258096-9 (2014)CrossRefGoogle Scholar
  173. 173.
    A.J. Vegas, O. Veiseh, M. Gürtler, J.R. Millman, F.W. Pagliuca, A.R. Bader, J.C. Doloff, J. Li, M. Chen, K. Olejnik, H.H. Tam, S. Jhunjhunwala, E. Langan, S. Aresta-DaSilva, S. Gandham, J.J. McGarrigle, M.A. Bochenek, J. Hollister-Lock, J. Oberholzer, D.L. Greiner, G.C. Weir, D.A. Melton, R. Langer, D.G. Anderson, Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat. Med. 22, 306–311 (2016)PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    O. Veiseh, J.C. Dolo, M. Ma, A.J. Vegas, H.H. Tam, A.R. Bader, J. Li, E. Langan, J. Wycko, W.S. Loo, S. Jhunjhunwala, A. Chiu, S. Siebert, K. Tang, J. Hollister-Lock, S. Aresta-Dasilva, M. Bochenek, J. Mendoza-Elias, Y. Wang, M. Qi, D.M. Lavin, M. Chen, N. Dholakia, R. Thakrar, I. Lacík, G.C. Weir, J. Oberholzer, D.L. Greiner, R. Langer, Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat. Mater. 14, 643–652 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  175. 175.
    A.J. Vegas, O. Veiseh, J.C. Doloff, M. Ma, H.H. Tam, K. Bratlie, J. Li, A.R. Bader, E. Langan, K. Olejnik, P. Fenton, J.W. Kang, J. Hollister-Locke, M.A. Bochenek, A. Chiu, S. Siebert, K. Tang, S. Jhunjhunwala, S. Aresta-DaSilva, N. Dholakia, R. Thakrar, T. Vietti, M. Chen, J. Cohen, K. Siniakowicz, M. Qi, J. McGarrigle, A.C. Graham, S. Lyle, D.M. Harlan, D.L. Greiner, J. Oberholzer, G.C. Weir, R. Langer, Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat. Biotechnol. 34, 345–352 (2016)PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Y. Zhu, T. Tchkonia, T. Pirtskhalava, A.C. Gower, H. Ding, N. Giorgadze, A.K. Palmer, Y. Ikeno, G.B. Hubbard, S.P.O. Hara, N.F. Larusso, D. Jordan, C.M. Roos, G.C. Verzosa, K. Nathan, J.D. Wren, J.N. Farr, M.B. Stout, S.J. McGowan, A.U. Gurkar, J. Zhao, A. Dorronsoro, Y.Y. Ling, S. Amira, D.C. Navarro, T. Sano, D. Paul, L.J. Niedernhofer, J.L. Kirkland, The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14, 644–658 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  177. 177.
    D.J. Baker, T. Wijshake, T. Tchkonia, N.K. Lebrasseur, B.G. Childs, B. Van De Sluis, J.L. Kirkland, J.M. Van Deursen, Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232–236 (2011)PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    D. Patra, S. Sengupta, W. Duan, H. Zhang, R. Pavlick, A. Sen, Intelligent, self-powered, drug delivery systems. Nanoscale 5, 1273–1283 (2013)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Chemical EngineeringMcMaster UniversityHamiltonCanada
  2. 2.EcoSynthetixBurlingtonCanada

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