||Chong Li, Jiancheng Wang, Yiguang Wang, Huile Gao, Gang Wei, Yongzhuo Huang, Haijun Yu, Yong Gan, Yongjun Wang, Lin Mei, Huabing Chen, Haiyan Hu, Zhiping Zhang, Yiguang Jin. Recent progress in drug delivery[J]. Acta Pharmaceutica Sinica B, 2019, 9(6): 1145-1162
|Recent progress in drug delivery
|Chong Lia, Jiancheng Wangb, Yiguang Wangb, Huile Gaoc, Gang Weid, Yongzhuo Huange, Haijun Yue, Yong Gane, Yongjun Wangf, Lin Meig, Huabing Chenh, Haiyan Hui, Zhiping Zhangj, Yiguang Jink
|a College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China;
b Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China;
c Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China;
d Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai 201203, China;
e Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
f School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;
g School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510275, China;
h School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China;
i School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China;
j School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;
k Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China
|Drug delivery systems (DDS) are defined as methods by which drugs are delivered to desired tissues, organs, cells and subcellular organs for drug release and absorption through a variety of drug carriers. Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility, drug aggregation, low bioavailability, poor biodistribution, lack of selectivity, or to reduce the side effects of therapeutic drugs. During 2015-2018, significant progress in the research on drug delivery systems has been achieved along with advances in related fields, such as pharmaceutical sciences, material sciences and biomedical sciences. This review provides a concise overview of current progress in this research area through its focus on the delivery strategies, construction techniques and specific examples. It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.
Drug delivery system
|Funds: This review paper was supported by the projects of National Natural Science Foundation of China (Grant Nos. 81773650, 81690264 and 81673376), the Drug Innovation Major Project of China (Grant No. 2018ZX09721003-004).
|Corresponding author: Jiancheng Wang
||1. Park K. Controlled drug delivery systems: past forward and future back. J Control Release 2014;190:3-8.
2. Barenholz Y. Doxil®-the first FDA-approved nano-drug: lessons learned. J Control Release 2012;160:117-34.
3. Kennon S, Tasch EG, Arm RN, Wig PP. The relationship between plaque scores and the development of caries in adult dentition. Clin Prev Dent 1979;1:26-31.
4. Li M, Shi KR, Tang X, Wei JJ, Cun XL, Chen XX, et al. pH-sensitive folic acid and dNP2 peptide dual-modified liposome for enhanced targeted chemotherapy of glioma. Eur J Pharm Sci 2018;124:240-8.
5. Zhang TH, Chen X, Xiao CS, Zhuang XL, Chen XS. Synthesis of a phenylboronic ester-linked PEG-lipid conjugate for ROS-responsive drug delivery. Polym Chem 2017;8:6209-16.
6. Chi YY, Yin XL, Sun KX, Feng SS, Liu JH, Chen DQ, et al. Redoxsensitive and hyaluronic acid functionalized liposomes for cytoplasmic drug delivery to osteosarcoma in animal models. J Control Release 2017;261:113-25.
7. Fouladi F, Steffen KJ, Mallik S. Enzyme-responsive liposomes for the delivery of anticancer drugs. Bioconjug Chem 2017;28:857-68.
8. Feng Y, Li NX, Yin HL, Chen TY, Yang Q, Wu M. Thermo-and pHresponsive, lipid-coated, mesoporous silica nanoparticle-based dual drug delivery system to improve the antitumor effect of hydrophobic drugs. Mol Pharm 2019;16:422-36.
9. Li QP, Li W, Di HX, Luo LH, Zhu CQ, Yang J, et al. A photosensitive liposome with NIR light triggered doxorubicin release as a combined photodynamic-chemo therapy system. J Control Release 2018;277:114-25.
10. Santos MA, Goertz DE, Hynynen K. Focused ultrasound hyperthermia mediated drug delivery using thermosensitive liposomes and visualized with in vivo two-photon microscopy. Theranostics 2017;7: 2718-31.
11. Salvatore A, Montis C, Berti D, Baglioni P. Multifunctional magnetoliposomes for sequential controlled release. ACS Nano 2016;10: 7749-60.
12. Deng W, Chen WJ, Clement S, Guller A, Zhao ZJ, Engel A, et al. Controlled gene and drug release from a liposomal delivery platform triggered by X-ray radiation. Nat Commun 2018;9:2713.
13. Rwei AY, Paris JL, Wang B, Wang WP, Axon CD, Vallet-Regí M, et al. Ultrasound-triggered local anaesthesia. Nat Biomed Eng 2017; 1:644-53.
14. Lv SX, Wu YC, Cai KM, He H, Li YJ, Lan M, et al. High drug loading and sub-quantitative loading efficiency of polymeric micelles driven by donor-receptor coordination interactions. J Am Chem Soc 2018;140:1235-8.
15. Wang TT, Wang DG, Liu JP, Feng B, Zhou FY, Zhang HW, et al. Acidity-triggered ligand-presenting nanoparticles to overcome sequential drug delivery barriers to tumors. Nano Lett 2017;17: 5429-36.
16. Li SP, Zhang YL, Wang J, Zhao Y, Ji TJ, Zhao X, et al. Nanoparticlemediated local depletion of tumour-associated platelets disrupts vascular barriers and augments drug accumulation in tumours. Nat Biomed Eng 2017;1:667-79.
17. Ling X, Chen X, Riddell IA, Tao W, Wang JQ, Hollett G, et al. Glutathione-scavenging poly(disulfide amide) nanoparticles for the effective delivery of Pt(IV) prodrugs and reversal of cisplatin resistance. Nano Lett 2018;18:4618-25.
18. Qian CG, Feng PJ, Yu JC, Chen YL, Hu QY, Sun WJ, et al. Anaerobe-inspired anticancer nanovesicles. Angew Chem Int Ed 2017;56:2588-93.
19. Deng ZY, Qian YF, Yu YQ, Liu GH, Hu JM, Zhang GY, et al. Engineering intracellular delivery nanocarriers and nanoreactors from oxidation-responsive polymersomes via synchronized bilayer crosslinking and permeabilizing inside live cells. J Am Chem Soc 2016; 138:10452-66.
20. Guo ZQ, Zou YL, He H, Rao JM, Ji SS, Cui XN, et al. Bifunctional platinated nanoparticles for photoinduced tumor ablation. Adv Mater 2016;28:10155-64.
21. Ye SY, Rao JM, Qiu SH, Zhao JL, He H, Yan ZL, et al. Rational design of conjugated photosensitizers with controllable photoconversion for dually cooperative phototherapy. Adv Mater 2018;30: 1801216.
22. Gao HL, He Q. The interaction of nanoparticles with plasma proteins and the consequent influence on nanoparticles behavior. Expert Opin Drug Deliv 2014;11:409-20.
23. Guan XW, Guo ZP, Wang TH, Lin L, Chen J, Tian HY, et al. A pHresponsive detachable PEG shielding strategy for gene delivery system in cancer therapy. Biomacromolecules 2017;18:1342-9.
24. Zeng Y, Zhou ZX, Fan MM, Gong T, Zhang ZR, Sun X. PEGylated cationic vectors containing a protease-sensitive peptide as a miRNA delivery system for treating breast cancer. Mol Pharm 2017;14: 81-92.
25. Gao HL, Zhang QY, Yu ZQ, He Q. Cell-penetrating peptide-based intelligent liposomal systems for enhanced drug delivery. Curr Pharm Biotechnol 2014;15:210-9.
26. Chen XL, Liu LS, Jiang C. Charge-reversal nanoparticles: novel targeted drug delivery carriers. Acta Pharm Sin B 2016;6:261-7.
27. Lv GX, Guo WS, Zhang W, Zhang TB, Li SY, Chen SZ, et al. Nearinfrared emission CuInS/ZnS quantum dots: all-in-one theranostic nanomedicines with intrinsic fluorescence/photoacoustic imaging for tumor phototherapy. ACS Nano 2016;10:9637-45.
28. Wang S, Huang P, Chen XY. Hierarchical targeting strategy for enhanced tumor tissue accumulation/retention and cellular internalization. Adv Mater 2016;28:7340-64.
29. Liu R, Xiao W, Hu C, Xie R, Gao HL. Theranostic size-reducible and no donor conjugated gold nanocluster fabricated hyaluronic acid nanoparticle with optimal size for combinational treatment of breast cancer and lung metastasis. J Control Release 2018;278:127-39.
30. Hu C, Cun XL, Ruan SB, Liu R, Xiao W, Yang XT, et al. Enzymetriggered size shrink and laser-enhanced NO release nanoparticles for deep tumor penetration and combination therapy. Biomaterials 2018; 168:64-75.
31. Ruan SB, Hu C, Tang X, Cun XL, Xiao W, Shi KR, et al. Increased gold nanoparticle retention in brain tumors by in situ enzymeinduced aggregation. ACS Nano 2016;10:10086-98.
32. Zhang P, Xu XY, Chen YP, Xiao MQ, Feng B, Tian KX, et al. Protein corona between nanoparticles and bacterial proteins in activated sludge: characterization and effect on nanoparticle aggregation. Bioresour Technol 2018;250:10-6.
33. Yang PP, Luo Q, Qi GB, Gao YJ, Li BN, Zhang JP, et al. Host materials transformable in tumor microenvironment for homing theranostics. Adv Mater 2017;29:1605869.
34. Subbiah V, Grilley-Olson JE, Combest AJ, Sharma N, Tran RH, Bobe I, et al. Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) plus gemcitabine in patients with advanced solid tumors. Clin Cancer Res 2018;24:43-51.
35. Zhang M, Liu EG, Cui Y, Huang YZ. Nanotechnology-based combination therapy for overcoming multidrug-resistant cancer. Cancer Biol Med 2017;14:212-27.
36. Peng HG, Chen BF, Huang W, Tang YB, Jiang YF, Zhang WY, et al. Reprogramming tumor-associated macrophages to reverse EGFRT790M resistance by dual-targeting codelivery of gefitinib/vorinostat. Nano Lett 2017;17:7684-90.
37. Kang XJ, Wang HY, Peng HG, Chen BF, Zhang WY, Wu AH, et al. Codelivery of dihydroartemisinin and doxorubicin in mannosylated liposomes for drug-resistant colon cancer therapy. Acta Pharmacol Sin 2017;38:885-96.
38. Kang XJ, Zheng ZN, Liu ZH, Wang HY, Zhao YG, Zhang WY, et al. Liposomal codelivery of doxorubicin and andrographolide inhibits breast cancer growth and metastasis. Mol Pharm 2018; 15:1618-26.
39. Kemp JA, Shim MS, Heo CY, Kwon YJ. “Combo” nanomedicine: co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy. Adv Drug Deliv Rev 2016;98:3-18.
40. Krauss AC, Gao X, Li L, Manning ML, Patel P, Fu WT, et al. FDA approval summary: (daunorubicin and cytarabine) liposome for injection for the treatment of adults with high-risk acute myeloid leukemia. Clin Cancer Res 2019;25:2685-90.
41. Cheng W, Nie JP, Gao NS, Liu G, Tao W, Xiao XJ, et al. A multifunctional nanoplatform against multidrug resistant cancer: merging the best of targeted chemo/gene/photothermal therapy. Adv Funct Mater 2017;27:1704135.
42. Zhang FW, Ni QQ, Jacobson O, Cheng SY, Liao A, Wang ZT, et al. Polymeric nanoparticles with a glutathione-sensitive heterodimeric multifunctional prodrug for in vivo drug monitoring and synergistic cancer therapy. Angew Chem Int Ed 2018;57:7066-70.
43. Mura S, Nicolas J, Couvreur P. Stimuli-responsive nanocarriers for drug delivery. Nat Mater 2013;12:991-1003.
44. Qiao H, Cui ZW, Yang SB, Ji DK, Wang YG, Yang Y, et al. Targeting osteocytes to attenuate early breast cancer bone metastasis by theranostic upconversion nanoparticles with responsive plumbagin release. ACS Nano 2017;11:7259-73.
45. Arranja AG, Pathak V, Lammers T, Shi Y. Tumor-targeted nanomedicines for cancer theranostics. Pharmacol Res 2017;115: 87-95.
46. Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer 2011;11: 671-7.
47. Li Y, Wang YG, Huang G, Gao JM. Cooperativity principles in selfassembled nanomedicine. Chem Rev 2018;118:5359-91.
48. Wang YG, Zhou KJ, Huang G, Hensley C, Huang XN, Ma XP, et al. A nanoparticle-based strategy for the imaging of a broad range of tumours by nonlinear amplification of microenvironment signals. Nat Mater 2014;13:204-12.
49. Zhao T, Huang G, Li Y, Yang SC, Ramezani S, Lin ZQ, et al. A transistor-like pH nanoprobe for tumour detection and image-guided surgery. Nat Biomed Eng 2016;1:0006.
50. Luo M, Wang H, Wang ZH, Cai HC, Lu ZG, Li Y, et al. A STINGactivating nanovaccine for cancer immunotherapy. Nat Nanotechnol 2017;12:648-54.
51. Xu XD, Wu J, Liu YL, Yu M, Zhao LL, Zhu X, et al. Ultra-pHresponsive and tumor-penetrating nanoplatform for targeted siRNA delivery with robust anti-cancer efficacy. Angew Chem Int Ed 2016; 55:7091-4.
52. Alkilany AM, Thompson LB, Boulos SP, Sisco PN, Murphy CJ. Gold nanorods: their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions. Adv Drug Deliv Rev 2012;64:190-9.
53. Shanmugam V, Selvakumar S, Yeh CS. Near-infrared lightresponsive nanomaterials in cancer therapeutics. Chem Soc Rev 2014;43:6254-87.
54. Morgan J, Oseroff AR. Mitochondria-based photodynamic anticancer therapy. Adv Drug Deliv Rev 2001;49:71-86.
55. Zhao X, Yang CX, Chen LG, Yan XP. Dual-stimuli responsive and reversibly activatable theranostic nanoprobe for precision tumortargeting and fluorescence-guided photothermal therapy. Nat Commun 2017;8:14998.
56. Xu ST, Zhu XY, Zhang C, Huang W, Zhou YF, Yan DY. Oxygen and Pt(II) self-generating conjugate for synergistic photo-chemo therapy of hypoxic tumor. Nat Commun 2018;9:2053.
57. Li XS, Kwon N, Guo T, Liu Z, Yoon J. Innovative strategies for hypoxic-tumor photodynamic therapy. Angew Chem Int Ed 2018;57: 11522-31.
58. Yue XL, Zhang Q, Dai ZF. Near-infrared light-activatable polymeric nanoformulations for combined therapy and imaging of cancer. Adv Drug Deliv Rev 2017;115:155-70.
59. Chen M, Liang XL, Gao C, Zhao RR, Zhang NS, Wang SM, et al. Ultrasound triggered conversion of porphyrin/camptothecinfluoroxyuridine triad microbubbles into nanoparticles overcomes multidrug resistance in colorectal cancer. ACS Nano 2018;12: 7312-26.
60. Shi JJ, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 2017;17:20-37.
61. Yu MK, Park J, Jon S. Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy. Theranostics 2012;2: 3-44.
62. Zou LL, Wang H, He B, Zeng LJ, Tan T, Cao HQ, et al. Current approaches of photothermal therapy in treating cancer metastasis with nanotherapeutics. Theranostics 2016;6:762-72.
63. Zhang PF, Liu G, Chen XY. Nanobiotechnology: cell membranebased delivery systems. Nano Today 2017;13:7-9.
64. Kumar S, Michael IJ, Park J, Granick S, Cho YK. Cloaked exosomes: biocompatible, durable, and degradable encapsulation. Small 2018; 14:1802052.
65. Ingato D, Edson JA, Zakharian M, Kwon YJ. Cancer cell-derived, drug-loaded nanovesicles induced by sulfhydryl-blocking for effective and safe cancer therapy. ACS Nano 2018;12:9568-77.
66. Xue JW, Zhao ZK, Zhang L, Xue LJ, Shen SY, Wen YJ, et al. Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence. Nat Nanotechnol 2017; 12:692-700.
67. Wu TT, Zhang D, Qiao Q, Qin XY, Yang CL, Kong M, et al. Biomimetic nanovesicles for enhanced antitumor activity of combinational photothermal and chemotherapy. Mol Pharm 2018;15: 1341-52.
68. Molinaro R, Corbo C, Martinez JO, Taraballi F, Evangelopoulos M, Minardi S, et al. Biomimetic proteolipid vesicles for targeting inflamed tissues. Nat Mater 2016;15:1037-46.
69. Xu C, Yang XY, Fu X, Tian R, Jacobson O, Wang ZT, et al. Converting red blood cells to efficient microreactors for blood detoxification. Adv Mater 2017;29:1603673.
70. Kaneti L, Bronshtein T, Malkah Dayan N, Kovregina I, Letko Khait N, Lupu-Haber Y, et al. Nanoghosts as a novel natural nonviral gene delivery platform safely targeting multiple cancers. Nano Lett 2016;16:1574-82.
71. Armstrong JPK, Holme MN, Stevens MM. Re-engineering extracellular vesicles as smart nanoscale therapeutics. ACS Nano 2017;11: 69-83.
72. Song QL, Yin YJ, Shang LH, Wu TT, Zhang D, Kong M, et al. Tumor microenvironment responsive nanogel for the combinatorial antitumor effect of chemotherapy and immunotherapy. Nano Lett 2017;17:6366-75.
73. Chen Z, Zhao PF, Luo ZY, Zheng MB, Tian H, Gong P, et al. Cancer cell membrane-biomimetic nanoparticles for homologous-targeting dual-modal imaging and photothermal therapy. ACS Nano 2016;10: 10049-57.
74. Kroll AV, Fang RH, Jiang Y, Zhou JR, Wei XL, Yu CL, et al. Nanoparticulate delivery of cancer cell membrane elicits multiantigenic antitumor immunity. Adv Mater 2017;29:1703969.
75. Kang T, Zhu QQ, Wei D, Feng JX, Yao JH, Jiang TZ, et al. Nanoparticles coated with neutrophil membranes can effectively treat cancer metastasis. ACS Nano 2017;11:1397-411.
76. Wu TT, Qi Y, Zhang D, Song QL, Yang CL, Hu XM, et al. Bone marrow dendritic cells derived microvesicles for combinational immunochemotherapy against tumor. Adv Funct Mater 2017;27: 1703191.
77. Usman WM, Pham TC, Kwok YY, Vu LT, Ma V, Peng BY, et al. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat Commun 2018;9:2359.
78. Kuai R, Ochyl LJ, Bahjat KS, Schwendeman A, Moon JJ. Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat Mater 2017;16:489-96.
79. Lizotte PH, Wen AM, Sheen MR, Fields J, Rojanasopondist P, Steinmetz NF, et al. In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer. Nat Nanotechnol 2016; 11:295-303.
80. Lebel ME, Chartrand K, Tarrab E, Savard P, Leclerc D, Lamarre A. Potentiating cancer immunotherapy using papaya mosaic virusderived nanoparticles. Nano Lett 2016;16:1826-32.
81. Johnsen KB, Bak M, Kempen PJ, Melander F, Burkhart A, Thomsen MS, et al. Antibody affinity and valency impact brain uptake of transferrin receptor-targeted gold nanoparticles. Theranostics 2018;8:3416-36.
82. Peng S, Wang YH, Li N, Li C. Enhanced cellular uptake and tumor penetration of nanoparticles by imprinting the “hidden” part of membrane receptors for targeted drug delivery. Chem Commun 2017; 53:11114-7.
83. Kedmi R, Veiga N, Ramishetti S, Goldsmith M, Rosenblum D, Dammes N, et al. A modular platform for targeted RNAi therapeutics. Nat Nanotechnol 2018;13:214-9.
84. Zheng YQ, Ji XY, Yu BC, Ji KL, Gallo D, Csizmadia E, et al. Enrichment-triggered prodrug activation demonstrated through mitochondria-targeted delivery of doxorubicin and carbon monoxide. Nat Chem 2018;10:787-94.
85. Scott LJ. Brentuximab vedotin: a review in CD30-positive hodgkin lymphoma. Drugs 2017;77:435-45.
86. Appelbaum FR, Bernstein ID. Gemtuzumab ozogamicin for acute myeloid leukemia. Blood 2017;130:2373-6.
87. Hurvitz SA, Martin M, Symmans WF, Jung KH, Huang CS, Thompson AM, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 2018;19: 115-26.
88. Oller-Salvia B, Sánchez-Navarro M, Ciudad S, Guiu M, ArranzGibert P, Garcia C, et al. MiniAp-4: a venom-inspired peptidomimetic for brain delivery. Angew Chem Int Ed 2016;55:572-5.
89. Guan J, Shen Q, Zhang Z, Jiang ZX, Yang Y, Lou MQ, et al. Enhanced immunocompatibility of ligand-targeted liposomes by attenuating natural IgM absorption. Nat Commun 2018;9:2982.
90. Sempkowski M, Zhu C, Menzenski MZ, Kevrekidis IG, Bruchertseifer F, Morgenstern A, et al. Sticky patches on lipid nanoparticles enable the selective targeting and killing of untargetable cancer cells. Langmuir 2016;32:8329-38.
91. Zhang Y, Deng CY, Liu S, Wu J, Chen ZB, Li C, et al. Active targeting of tumors through conformational epitope imprinting. Angew Chem Int Ed 2015;54:5157-60.
92. Liu S, Bi QY, Long YY, Li ZX, Bhattacharyya S, Li C. Inducible epitope imprinting: ’generating’ the required binding site in membrane receptors for targeted drug delivery. Nanoscale 2017;9: 5394-7.
93. Norman J, Madurawe RD, Moore CMV, Khan MA, Khairuzzaman A. A new chapter in pharmaceutical manufacturing: 3D-printed drug products. Adv Drug Deliv Rev 2017;108:39-50.
94. Giordano RA, Wu BM, Borland SW, Cima LG, Sachs EM, Cima MJ. Mechanical properties of dense polylactic acid structures fabricated by three dimensional printing. J Biomater Sci Polym Ed 1996;8: 63-75.
95. Talebian S, Foroughi J, Wade SJ, Vine KL, Dolatshahi-Pirouz A, Mehrali M, et al. Biopolymers for antitumor implantable drug delivery systems: recent advances and future outlook. Adv Mater 2018; 30:1706665.
96. Goyanes A, Buanz ABM, Basit AW, Gaisford S. Fused-filament 3D printing (3DP) for fabrication of tablets. Int J Pharm 2014;476: 88-92.
97. Khaled SA, Burley JC, Alexander MR, Yang J, Roberts CJ. 3D printing of five-in-one dose combination polypill with defined immediate and sustained release profiles. J Control Release 2015;217: 308-14.
98. Kyobula M, Adedeji A, Alexander MR, Saleh E, Wildman R, Ashcroft I, et al. 3D inkjet printing of tablets exploiting bespoke complex geometries for controlled and tuneable drug release. J Control Release 2017;261:207-15.
99. Gupta MK, Meng FB, Johnson BN, Kong YL, Tian LM, Yeh YW, et al. 3D printed programmable release capsules. Nano Lett 2015;15: 5321-9.
100. Yang FY, Su YC, Zhang JT, Dinunzio J, Leone A, Huang CB, et al. Rheology guided rational selection of processing temperature to prepare copovidone/nifedipine amorphous solid dispersions via hot melt extrusion (HME). Mol Pharm 2016;13:3494-505.
101. Bochmann ES, Neumann D, Gryczke A, Wagner KG. Micro-scale prediction method for API-solubility in polymeric matrices and process model for forming amorphous solid dispersion by hot-melt extrusion. Eur J Pharm Biopharm 2016;107:40-8.
102. Skowyra J, Pietrzak K, Alhnan MA. Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing. Eur J Pharm Sci 2015;68:11-7.
103. Holländer J, Genina N, Jukarainen H, Khajeheian M, Rosling A, Mäkilä E, et al. Three-dimensional printed PCL-based implantable prototypes of medical devices for controlled drug delivery. J Pharm Sci 2016;105:2665-76.
104. Goyanes A, Det-Amornrat U, Wang J, Basit AW, Gaisford S. 3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems. J Control Release 2016; 234:41-8.
105. Li QJ, Wen HY, Jia DY, Guan XY, Pan H, Yang Y, et al. Preparation and investigation of controlled-release glipizide novel oral device with three-dimensional printing. Int J Pharm 2017;525:5-11.
106. Boetker J, Water JJ, Aho J, Arnfast L, Bohr A, Rantanen J. Modifying release characteristics from 3D printed drug-eluting products. Eur J Pharm Sci 2016;90:47-52.
107. Goole J, Amighi K. 3D printing in pharmaceutics: a new tool for designing customized drug delivery systems. Int J Pharm 2016;499: 376-94.
108. Ma GJ, Wu CW. Microneedle, bio-microneedle and bio-inspired microneedle: a review. J Control Release 2017;251:11-23.
109. Kwon KM, Lim SM, Choi S, Kim DH, Jin HE, Jee G, et al. Microneedles: quick and easy delivery methods of vaccines. Clin Exp Vaccine Res 2017;6:156-9.
110. Yang HW, Ye L, Guo XD, Yang CL, Compans RW, Prausnitz MR. Ebola vaccination using a DNA vaccine coated on PLGA-PLL/γPGA nanoparticles administered using a microneedle patch. Adv Healthc Mater 2017;6:1600750.
111. Johnson KL, McCann CM, Wilkinson JL, Jones M, Tebo BM, West M, et al. Dissolved Mn(III) in water treatment works: prevalence and significance. Water Res 2018;140:181-90.
112. Than A, Liu CH, Chang H, Duong PK, Cheung CMG, Xu CJ, et al. Self-implantable double-layered micro-drug-reservoirs for efficient and controlled ocular drug delivery. Nat Commun 2018;9:4433.
113. Jin X, Zhu DD, Chen BZ, Ashfaq M, Guo XD. Insulin delivery systems combined with microneedle technology. Adv Drug Deliv Rev 2018;127:119-37.
114. Bhatnagar S, Dave K, Venuganti VVK. Microneedles in the clinic. J Control Release 2017;260:164-82.
115. Lee H, Choi TK, Lee YB, Cho HR, Ghaffari R, Wang L, et al. A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy. Nat Nanotechnol 2016;11:566-72.
116. Lee H, Song C, Hong YS, Kim MS, Cho HR, Kang T, et al. Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module. Sci Adv 2017;3:e1601314.
117. Yu JC, Zhang YQ, Ye YQ, DiSanto R, Sun WJ, Ranson D, et al. Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery. Proc Natl Acad Sci U S A 2015;112:8260-5.
118. Yu JC, Qian CG, Zhang YQ, Cui Z, Zhu Y, Shen QD, et al. Hypoxia and H2O2 dual-sensitive vesicles for enhanced glucose-responsive insulin delivery. Nano Lett 2017;17:733-9.
119. Tong Z, Zhou J, Zhong J, Tang Q, Lei Z, Luo H, et al. Glucose-and H2O2-responsive polymeric vesicles integrated with microneedle patches for glucose-sensitive transcutaneous delivery of insulin in diabetic rats. ACS Appl Mater Interfaces 2018;10:20014-24.
120. Zhang YQ, Yu JC, Wang JQ, Hanne NJ, Cui Z, Qian CG, et al. Thrombin-responsive transcutaneous patch for auto-anticoagulant regulation. Adv Mater 2017;29:1604043.
121. Hirobe S, Azukizawa H, Hanafusa T, Matsuo K, Quan YS, Kamiyama F, et al. Clinical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch. Biomaterials 2015;57:50-8.
122. Arya J, Henry S, Kalluri H, McAllister DV, Pewin WP, Prausnitz MR. Tolerability, usability and acceptability of dissolving microneedle patch administration in human subjects. Biomaterials 2017;128:1-7.
123. Malamatari M, Taylor KMG, Malamataris S, Douroumis D, Kachrimanis K. Pharmaceutical nanocrystals: production by wet milling and applications. Drug Discov Today 2018;23:534-47.
124. Sigfridsson K, Skantze P, Skantze U, Svensson L, Löfgren L, Nordell P, et al. Nanocrystal formulations of a poorly soluble drug. 2. Evaluation of nanocrystal liver uptake and distribution after intravenous administration to mice. Int J Pharm 2017;524:248-56.
125. Bi C, Miao XQ, Chow SF, Wu WJ, Yan R, Liao YH, et al. Particle size effect of curcumin nanosuspensions on cytotoxicity, cellular internalization, in vivo pharmacokinetics and biodistribution. Nanomedicine 2017;13:943-53.
126. Abdelaziz HM, Gaber M, Abd-Elwakil MM, Mabrouk MT, Elgohary MM, Kamel NM, et al. Inhalable particulate drug delivery systems for lung cancer therapy: nanoparticles, microparticles, nanocomposites and nanoaggregates. J Control Release 2018;269:374-92.
127. Yang L, Hong J, Di J, Guo Y, Han M, Liu M, et al. 10-Hydroxycamptothecin (HCPT) nanosuspensions stabilized by mPEG1000-HCPT conjugate: high stabilizing efficiency and improved antitumor efficacy. Int J Nanomed 2017;12:3681-95.
128. Li YJ, Hong JY, Li HW, Qi XY, Guo YF, Han MH, et al. Genkwanin nanosuspensions: a novel and potential antitumor drug in breast carcinoma therapy. Drug Deliv 2017;24:1491-500.
129. Hadiwinoto GD, Lip Kwok PC, Lakerveld R. A review on recent technologies for the manufacture of pulmonary drugs. Ther Deliv 2018;9:47-70.
130. Hidalgo A, Cruz A, Pérez-Gil J. Pulmonary surfactant and nanocarriers: toxicity versus combined nanomedical applications. Biochim Biophys Acta 2017;1859:1740-8.
131. Khurana LK, Singh R, Singh H, Sharma M. Systematic development and optimization of an in-situ gelling system for moxifloxacin ocular nanosuspension using high-pressure homogenization with an improved encapsulation efficiency. Curr Pharm Des 2018;24: 1434-45.
132. Maged A, Mahmoud AA, Ghorab MM. Nano spray drying technique as a novel approach to formulate stable econazole nitrate nanosuspension formulations for ocular use. Mol Pharm 2016;13: 2951-65.
133. Romero GB, Keck CM, Müller RH, Bou-Chacra NA. Development of cationic nanocrystals for ocular delivery. Eur J Pharm Biopharm 2016;107:215-22.
134. Pelikh O, Stahr PL, Huang J, Gerst M, Scholz P, Dietrich H, et al. Nanocrystals for improved dermal drug delivery. Eur J Pharm Biopharm 2018;128:170-8.
135. Pireddu R, Caddeo C, Valenti D, Marongiu F, Scano A, Ennas G, et al. Diclofenac acid nanocrystals as an effective strategy to reduce in vivo skin inflammation by improving dermal drug bioavailability. Colloids Surf B Biointerfaces 2016;143:64-70.
136. Suri GS, Kaur A, Sen T. A recent trend of drug-nanoparticles in suspension for the application in drug delivery. Nanomedicine 2016; 11:2861-76.
137. Chang TL, Zhan HL, Liang DN, Liang JF. Nanocrystal technology for drug formulation and delivery. Front Chem Sci Eng 2015;9:1-14.
138. Romero GB, Keck CM, Müller RH. Simple low-cost miniaturization approach for pharmaceutical nanocrystals production. Int J Pharm 2016;501:236-44.
139. Han XF, Wang ML, Ma ZH, Xue P, Wang YJ. A new approach to produce drug nanosuspensions CO2-assisted effervescence to produce drug nanosuspensions. Colloids Surf B Biointerfaces 2016;143: 107-10.
140. Wang YL, Han XF, Wang J, Wang YJ. Preparation, characterization and in vivo evaluation of amorphous tacrolimus nanosuspensions produced using CO2-assisted in situ nanoamorphization method. Int J Pharm 2016;505:35-41.
141. Amly W, Karaman R. Recent updates in utilizing prodrugs in drug delivery (2013-2015). Exp Opin Drug Deliv 2016;13:571-91.
142. Du L, Jia JW, Ge PJ, Jin YG. Self-assemblies of 50-cholesteryl-ethylphosphoryl zidovudine. Colloid Surf B Biointerfaces 2016;148: 385-91.
143. Gaudin A, Yemisci M, Eroglu H, Lepetre-Mouelhi S, Turkoglu OF, Dönmez-Demir B, et al. Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury. Nat Nanotechnol 2014;9:1054-62.
144. Sarett SM, Werfel TA, Chandra I, Jackson MA, Kavanaugh TE, Hattaway ME, et al. Hydrophobic interactions between polymeric carrier and palmitic acid-conjugated siRNA improve PEGylated polyplex stability and enhance in vivo pharmacokinetics and tumor gene silencing. Biomaterials 2016;97:122-32.
145. Du L, Zhang BL, Lei YJ, Wang S, Jin YG. Long-circulating and liver-targeted nanoassemblies of cyclic phosphoryl N-dodecanoyl gemcitabine for the treatment of hepatocellular carcinoma. Biomed Pharmacother 2016;79:208-14.
146. Cheetham AG, Zhang PC, Lin YA, Lock LL, Cui HG. Supramolecular nanostructures formed by anticancer drug assembly. J Am Chem Soc 2013;135:2907-10.
147. Couvreur P, Stella B, Reddy LH, Hillaireau H, Dubernet C, Desmaële D, et al. Squalenoyl nanomedicines as potential therapeutics. Nano Lett 2006;6:2544-8.
148. Huang XX, Liao WB, Xie ZH, Chen DS, Zhang CY. A pHresponsive prodrug delivery system self-assembled from acid-labile doxorubicin-conjugated amphiphilic pH-sensitive block copolymers. Mater Sci Eng C 2018;90:27-37.
149. Zuo J, Tong L, Du L, Yang M, Jin YG. Biomimetic nanoassemblies of 1-O-octodecyl-2-conjugated linoleoyl-sn-glycero-3-phosphatidyl gemcitabine with phospholipase A2-triggered degradation for the treatment of cancer. Colloids Surf B Biointerfaces 2017;152:467-74.
150. Luo C, Sun J, Sun BJ, Liu D, Miao L, Goodwin TJ, et al. Facile fabrication of tumor redox-sensitive nanoassemblies of smallmolecule oleate prodrug as potent chemotherapeutic nanomedicine. Small 2016;12:6353-62.
151. Rautio J, Kumpulainen H, Heimbach T, Oliyai R, Oh D, Järvinen T, et al. Prodrugs: design and clinical applications. Nat Rev Drug Discov 2008;7:255-70.
152. Du L, Wu LL, Jin YG, Jia JW, Li M, Wang Y. Self-assembled drug delivery systems. Part 7: hepatocyte-targeted nanoassemblies of an adefovir lipid derivative with cytochrome P450-triggered drug release. Int J Pharm 2014;472:1e9.
153. Zhang JM, Song HJ, Ji SL, Wang XM, Huang PS, Zhang CN, et al. NO prodrug-conjugated, self-assembled, pH-responsive and galactose receptor targeted nanoparticles for co-delivery of nitric oxide and doxorubicin. Nanoscale 2018;10:4179e88.
154. Han LQ, Wang TQ, Wu JL, Yin XL, Fang H, Zhang N. A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy. Int J Nanomed 2016;11:6003e22.
155. Luo C, Sun J, Liu D, Sun BJ, Miao L, Musetti S, et al. Selfassembled redox dual-responsive prodrug-nanosystem formed by single thioether-bridged paclitaxel-fatty acid conjugate for cancer chemotherapy. Nano Lett 2016;16:5401e8.
156. Meng H, Zou Y, Zhong P, Meng FH, Zhang J, Cheng R, et al. A smart nano-prodrug platform with reactive drug loading, superb stability, and fast responsive drug release for targeted cancer therapy. Macromol Biosci 2017;17:1600518.
157. Huang D, Zhuang YP, Shen H, Yang F, Wang X, Wu DC. Acetallinked PEGylated paclitaxel prodrugs forming free-paclitaxel-loaded pH-responsive micelles with high drug loading capacity and improved drug delivery. Mater Sci Eng C 2018;82:60e8.
158. Tao W, Zhu XB, Yu XH, Zeng XW, Xiao QL, Zhang XD, et al. Black phosphorus nanosheets as a robust delivery platform for cancer theranostics. Adv Mater 2017;29:1603276.
159. Zhou YX, Quan GL, Wu QL, Zhang XX, Niu BY, Wu BY, et al. Mesoporous silica nanoparticles for drug and gene delivery. Acta Pharm Sin B 2018;8:165e77.
160. Zeng XW, Liu G, Tao W, Ma Y, Zhang XD, He F, et al. A drug-selfgated mesoporous antitumor nanoplatform based on pH-sensitive dynamic covalent bond. Adv Funct Mater 2017;27:1605985.
161. Ji XY, Kong N, Wang JQ, Li WL, Xiao YL, Gan ST, et al. A novel top-down synthesis of ultrathin 2D boron nanosheets for multimodal imaging-guided cancer therapy. Adv Mater 2018;36:1803031.
162. Kim CK, Ghosh P, Rotello VM. Multimodal drug delivery using gold nanoparticles. Nanoscale 2009;1:61e7.
163. El-Sherbiny IM, Elbaz NM, Sedki M, Elgammal A, Yacoub MH. Magnetic nanoparticles-based drug and gene delivery systems for the treatment of pulmonary diseases. Nanomedicine 2017;12: 387e402.
164. Yao J, Li PF, Li L, Yang M. Biochemistry and biomedicine of quantum dots: from biodetection to bioimaging, drug discovery, diagnostics, and therapy. Acta Biomater 2018;74:36e55.
165. Liu JQ, Cui L, Losic D. Graphene and graphene oxide as new nanocarriers for drug delivery applications. Acta Biomater 2013;9: 9243e57.
166. Xu TT, Xu XY, Gu Y, Fang L, Cao F. Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery. Int J Nanomed 2018;13:917e37.
167. Liang RZ, Wei M, Evans DG, Duan X. Inorganic nanomaterials for bioimaging, targeted drug delivery and therapeutics. Chem Commun 2014;50:14071e81.
168. Chen TT, Yi JT, Zhao YY, Chu X. Biomineralized metal-organic framework nanoparticles enable intracellular delivery and endolysosomal release of native active proteins. J Am Chem Soc 2018; 140:9912e20.
169. He B, Shi YJ, Liang YQ, Yang AP, Fan ZP, Yuan L, et al. Singlewalled carbon-nanohorns improve biocompatibility over nanotubes by triggering less protein-initiated pyroptosis and apoptosis in macrophages. Nat Commun 2018;9:2393.
170. Schleich N, Po C, Jacobs D, Ucakar B, Gallez B, Danhier F, et al. Comparison of active, passive and magnetic targeting to tumors of multifunctional paclitaxel/SPIO-loaded nanoparticles for tumor imaging and therapy. J Control Release 2014;194:82e91.
171. Chen F, Zhao ER, Hableel G, Hu T, Kim T, Li JT, et al. Increasing the efficacy of stem cell therapy via triple-function inorganic nanoparticles. ACS Nano 2019;13:6605e17.
172. Gao WX, Hu YL, Xu L, Liu MC, Wu HY, He B. Dual pH and glucose sensitive gel gated mesoporous silica nanoparticles for drug delivery. Chin Chem Lett 2018;29:1795e8.
173. Cheng W, Liang CY, Xu L, Liu G, Gao NS, Tao W, et al. TPGSfunctionalized polydopamine-modified mesoporous silica as drug nanocarriers for enhanced lung cancer chemotherapy against multidrug resistance. Small 2017;13:1700623.
174. Quan GL, Pan X, Wang ZH, Wu QL, Li G, Dian LH, et al. Erratum to: lactosaminated mesoporous silica nanoparticles for asialoglycoprotein receptor targeted anticancer drug delivery. J Nanobiotechnol 2015;13:89.
175. Shen DK, Yang JP, Li XM, Zhou L, Zhang RY, Li W, et al. Biphase stratification approach to three-dimensional dendritic biodegradable mesoporous silica nanospheres. Nano Lett 2014;14:923e32.
176. Choi E, Kim S. Surface pH buffering to promote degradation of mesoporous silica nanoparticles under a physiological condition. J Colloid Interface Sci 2019;533:463e70.
177. Song Y, Li Y, Xu Q, Liu Z. Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery: advances, challenges, and outlook. Int J Nanomed 2016;12:87e110.
178. Su JH, Sun HP, Meng QS, Zhang PC, Yin Q, Li YP. Enhanced blood suspensibility and laser-activated tumor-specific drug release of theranostic mesoporous silica nanoparticles by functionalizing with erythrocyte membranes. Theranostics 2017;7:523e37.
179. Chai SQ, Guo Y, Zhang ZY, Chai Z, Ma YR, Qi LM. Cyclodextringated mesoporous silica nanoparticles as drug carriers for red lightinduced drug release. Nanotechnology 2017;28:145101.
180. Zhao YT, Wang HY, Huang H, Xiao QL, Xu YH, Guo ZN, et al. Surface coordination of black phosphorus for robust air and water stability. Angew Chem Int Ed 2016;55:5003e7.
181. Zeng XW, Luo MM, Liu G, Wang XS, Tao W, Lin YX, et al. Polydopamine-modified black phosphorous nanocapsule with enhanced stability and photothermal performance for tumor multimodal treatments. Adv Sci 2018;5:1800510.
182. Morrison C. Alnylam prepares to land first RNAi drug approval. Nat Rev Drug Discov 2018;17:156e7.
183. Khalil IA, Yamada Y, Harashima H. Optimization of siRNA delivery to target sites: issues and future directions. Expert Opin Drug Deliv 2018;15:1053e65.
184. Wang HX, Song ZY, Lao YH, Xu X, Gong J, Cheng D, et al. Nonviral gene editing via CRISPR/Cas9 delivery by membranedisruptive and endosomolytic helical polypeptide. Proc Natl Acad Sci U S A 2018;115:4903e8.
185. Guan XW, Guo ZP, Lin L, Chen J, Tian HY, Chen XS. Ultrasensitive pH triggered charge/size dual-rebound gene delivery system. Nano Lett 2016;16:6823e31.
186. Zou Y, Zheng M, Yang WJ, Meng FH, Miyata K, Kim HJ, et al. Virus-mimicking chimaeric polymersomes boost targeted cancer siRNA therapy in vivo. Adv Mater 2017;29:1703285.
187. Li L, Muñozculla M, Carmona U, Lopez MP, Yang F, Trigueros C, et al. Ferritin-mediated siRNA delivery and gene silencing in human tumor and primary cells. Biomaterials 2016;98:143e51.
188. Xu XD, Saw PE, Tao W, Li YJ, Ji XY, Yu M, et al. Tumor microenvironment-responsive multistaged nanoplatform for systemic RNAi and cancer therapy. Nano Lett 2017;17:4427e35.
189. Wang B, Ding YP, Zhao XZ, Han XX, Yang N, Zhang YL, et al. Delivery of small interfering RNA against Nogo-B receptor via tumor-acidity responsive nanoparticles for tumor vessel normalization and metastasis suppression. Biomaterials 2018;175:110e22.
190. Chen Y, Gao DY, Huang L. In vivo delivery of miRNAs for cancer therapy: challenges and strategies. Adv Drug Deliv Rev 2015;81: 128e41.
191. He SF, Fan WW, Wu N, Zhu JJ, Miao YQ, Miao XR, et al. Lipidbased liquid crystalline nanoparticles facilitate cytosolic delivery of siRNA via structural transformation. Nano Lett 2018;18:2411e9.
192. Wang H, Agarwal P, Zhao ST, Yu JH, Lu XB, He XM. A nearinfrared laser-activated “Nanobomb” for breaking the barriers to microRNA delivery. Adv Mater 2016;28:347e55.
193. He H, Zheng N, Song ZY, Kim KH, Yao C, Zhang RJ, et al. Suppression of hepatic inflammation via systemic siRNA delivery by membrane-disruptive and endosomolytic helical polypeptide hybrid nanoparticles. ACS Nano 2016;10:1859e70.
194. Morrison C. Fresh from the biotech pipeline-2017. Nat Biotechnol 2018;36:131e6.
195. Viola M, Sequeira J, Seiça R, Veiga F, Serra J, Santos AC, et al. Subcutaneous delivery of monoclonal antibodies: how do we get there?. J Control Release 2018;286:301e14.
196. Ye C, Chi H. A review of recent progress in drug and protein encapsulation: approaches, applications and challenges. Mater Sci Eng C 2018;83:233e46.
197. Sahoo JK, VandenBerg MA, Webber MJ. Injectable network biomaterials via molecular or colloidal self-assembly. Adv Drug Deliv Rev 2018;127:185e207.
198. Wagner AM, Gran MP, Peppas NA. Designing the new generation of intelligent biocompatible carriers for protein and peptide delivery. Acta Pharm Sin B 2018;8:147e64.
199. Lakkireddy HR, Urmann M, Besenius M, Werner U, Haack T, Brun P, et al. Oral delivery of diabetes peptidesdcomparing standard formulations incorporating functional excipients and nanotechnologies in the translational context. Adv Drug Deliv Rev 2016;106: 196e222.
200. Koetting MC, Guido JF, Gupta M, Zhang A, Peppas NA. pHresponsive and enzymatically-responsive hydrogel microparticles for the oral delivery of therapeutic proteins: effects of protein size, crosslinking density, and hydrogel degradation on protein delivery. J Control Release 2016;221:18e25.
201. Mahmood A, Bernkop-Schnürch A. SEDDS: a game changing approach for the oral administration of hydrophilic macromolecular drugs. Adv Drug Deliv Rev 2018;142:91e101.
202. Batista P, Castro PM, Madureira AR, Sarmento B, Pintado M. Recent insights in the use of nanocarriers for the oral delivery of bioactive proteins and peptides. Peptides 2018;101:112e23.
203. Maisel K, Ensign L, Reddy M, Cone R, Hanes J. Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse. J Control Release 2015;197:48e57.
204. Wu JW, Zheng YX, Liu M, Shan W, Zhang ZR, Huang Y. Biomimetic viruslike and charge reversible nanoparticles to sequentially overcome mucus and epithelial barriers for oral insulin delivery. ACS Appl Mater Interfaces 2018;10:9916e28.
205. Yu MR, Wang JL, Yang YW, Zhu CL, Su Q, Guo SY, et al. Rotationfacilitated rapid transport of nanorods in mucosal tissues. Nano Lett 2016;16:7176e82.
206. Yu MR, Xu L, Tian FL, Su Q, Zheng N, Yang YW, et al. Rapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers. Nat Commun 2018;9:2607.
207. Pridgen EM, Alexis F, Kuo TT, Levy-Nissenbaum E, Karnik R, Blumberg RS, et al. Transepithelial transport of Fc-targeted nanoparticles by the neonatal Fc receptor for oral delivery. Sci Transl Med 2013;5:213ra167.
208. Kim KS, Suzuki K, Cho H, Youn YS, Bae YH. Oral nanoparticles exhibit specific high-efficiency intestinal uptake and lymphatic transport. ACS Nano 2018;12:8893e900.
209. Al-Hilal TA, Park J, Alam F, Chung SW, Park JW, Kim K, et al. Oligomeric bile acid-mediated oral delivery of low molecular weight heparin. J Control Release 2014;175:17e24.
210. Shan W, Zhu X, Liu M, Li L, Zhong JJ, Sun W, et al. Overcoming the diffusion barrier of mucus and absorption barrier of epithelium by self-assembled nanoparticles for oral delivery of insulin. ACS Nano 2015;9:2345e56.
211. Fan WW, Xia DN, Zhu QL, Li XY, He SF, Zhu CL, et al. Functional nanoparticles exploit the bile acid pathway to overcome multiple barriers of the intestinal epithelium for oral insulin delivery. Biomaterials 2018;151:13e23.
212. Moroz E, Matoori S, Leroux JC. Oral delivery of macromolecular drugs: where we are after almost 100 years of attempts. Adv Drug Deliv Rev 2016;101:108e21.
213. Chuang EY, Nguyen GTH, Su FY, Lin KJ, Chen CT, Mi FL, et al. Combination therapy via oral co-administration of insulin- and exendin-4-loaded nanoparticles to treat type 2 diabetic rats undergoing OGTT. Biomaterials 2013;34:7994e8001.
214. de Kruijf W, Ehrhardt C. Inhalation delivery of complex drugs-the next steps. Curr Opin Pharmacol 2017;36:52e7.
215. Bodier-Montagutelli E, Mayor A, Vecellio L, Respaud R, HeuzeVourc’h N. Designing inhaled protein therapeutics for topical lung delivery: what are the next steps?. Expert Opin Drug Deliv 2018;15: 729e36.
216. Mandal A, Pal D, Agrahari V, Trinh HM, Joseph M, Mitra AK. Ocular delivery of proteins and peptides: challenges and novel formulation approaches. Adv Drug Deliv Rev 2018;126:67e95.
217. Thwala LN, Pre át V, Csaba NS. Emerging delivery platforms for mucosal administration of biopharmaceuticals: a critical update on nasal, pulmonary and oral routes. Expert Opin Drug Deliv 2017;14: 23e36.
218. Ye YQ, Yu JC, Wen D, Kahkoska AR, Gu Z. Polymeric microneedles for transdermal protein delivery. Adv Drug Deliv Rev 2018;127: 106e18.
219. Yu JC, Zhang YQ, Kahkoska AR, Gu Z. Bioresponsive transcutaneous patches. Curr Opin Biotechnol 2017;48:28e32.
220. Hu XL, Yu JC, Qian CG, Lu Y, Kahkoska AR, Xie ZG, et al. H2O2- responsive vesicles integrated with transcutaneous patches for glucose-mediated insulin delivery. ACS Nano 2017;11:613e20.
221. Qiu C, Wei W, Sun J, Zhang HT, Ding JS, Wang JC, et al. Systemic delivery of siRNA by hyaluronan-functionalized calcium phosphate nanoparticles for tumor-targeted therapy. Nanoscale 2016;8: 13033e44.
222. Wang C, Ye YQ, Hochu GM, Sadeghifar H, Gu Z. Enhanced cancer immunotherapy by microneedle patch-assisted delivery of Anti-PD1 antibody. Nano Lett 2016;16:2334e40.
223. Ehlerding EB, England CG, Majewski RL, Valdovinos HF, Jiang DW, Liu G, et al. ImmunoPET imaging of CTLA-4 expression in mouse models of non-small cell lung cancer. Mol Pharm 2017;14: 1782e9.
224. Wang C, Sun WJ, Wright G, Wang AZ, Gu Z. Inflammation-triggered cancer immunotherapy by programmed delivery of CpG and Anti-PD1 antibody. Adv Mater 2016;28:8912e20.