Is the oral route possible for peptide and protein drug delivery?
Abstract
Oral delivery of peptides and proteins remains an attractive alternative to parenteral delivery and has challenged various attempts at delivery development. Incorporation of new tools into the delivery systems that can raise membrane permeability of macromolecules is essential to attain high oral bioavailability that is acceptable in clinical applications. In developing oral protein delivery systems with high bioavailability, three practical approaches might be most helpful: (1) modification of the physicochemical properties of macromolecules; (2) addition of novel function to macromolecules; or (3) use of improved delivery carriers. Clearly, it is essential that these approaches maintain the biological activity of the proteins.
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The limited bioavailability of orally administered mAbs is due to limited penetration across the intestinal epithelium and susceptibility to enzymatic degradation by proteases and peptidases in the intestinal lumen.
“The limited bioavailability of orally administered mAbs is due to their limited penetration across the intestinal epithelium16 and susceptibility to enzymatic degradation by proteases and peptidases in the intestinal lumen.17”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [16]
Cites
In Vivo Protein Transduction: Delivery of a Biologically Active Protein into the Mouse
Schwarze, S. R., Ho, A. L., Vocero-Akbani, A. M., & Dowdy, S. F. (1999) · Science · doi:10.1126/science.285.5433.1569 · Cited by 2,418 · see citing works
Lewin, M., Carlesso, N., Tung, C., Tang, X. S., Cory, D. G., Scadden, D. T., & Weissleder, R. (2000) · Nature Biotechnology · doi:10.1038/74464 · Cited by 1,716 · see citing works
Tat-mediated delivery of heterologous proteins into cells.
Fawell, S. E., Seery, J., Daikh, Y., Moore, C., Chen, L. L., Pepinsky, B., & Barsoum, J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.2.664 · Cited by 1,225 · see citing works
Protein drug stability: a formulation challenge
Frøkjær, S., & Otzen, D. E. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1695 · Cited by 1,102 · see citing works
The Mechanism of Uptake of Biodegradable Microparticles in Caco-2 Cells Is Size Dependent
Desai, M. P., Labhasetwar, V., Walter, E., Levy, R. J., & Amidon, G. L. (1997) · Pharmaceutical Research · doi:10.1023/a:1012126301290 · Cited by 858 · see citing works
Cell-penetrating peptides: mechanism and kinetics of cargo delivery
Zorko, M., & Langel, Ü. (2005) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2004.10.010 · Cited by 799 · see citing works
Torchilin, V. P., Rammohan, R., Weissig, V., & Levchenko, T. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151247498 · Cited by 777 · see citing works
Pan, Y., Li, Y.-J., Zhao, H.-Y., Zheng, J.-M., Xu, H., Wei, G., Hao, J.-S., & Fu-de, C. (2002) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(02)00486-6 · Cited by 686 · see citing works
Thiomers: A new generation of mucoadhesive polymers
Bernkop‐Schnürch, A. (2005) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2005.07.002 · Cited by 610 · see citing works
Close-Range Electrostatic Interactions in Proteins
Kumar, S., & Nussinov, R. (2002) · ChemBioChem · doi:10.1002/1439-7633(20020703)3:7 · Cited by 548 · see citing works
Challenges for the oral delivery of macromolecules
Goldberg, M. F., & Gómez-Orellana, I. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1067 · Cited by 545 · see citing works
Oral Delivery of Peptide Drugs
Hamman, J. H., Enslin, G. M., & Kotz, A. F. (2005) · BioDrugs · doi:10.2165/00063030-200519030-00003 · Cited by 504 · see citing works
Polymeric micelles for drug delivery
Aliabadi, H. M., & Lavasanifar, A. (2005) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.3.1.139 · Cited by 450 · see citing works
Tkachenko, A. G., Xie, H., Liu, Y., Coleman, D. M., Ryan, J. A., Glomm, W. R., Shipton, M. K., Franzen, S., & Feldheim, D. L. (2004) · Bioconjugate Chemistry · doi:10.1021/bc034189q · Cited by 449 · see citing works
P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement
Varma, M. V. S. (2003) · Pharmacological Research · doi:10.1016/s1043-6618(03)00158-0 · Cited by 420 · see citing works
Damgé, C., Michel, C., Aprahamian, M., & Couvreur, P. (1988) · Diabetes · doi:10.2337/diab.37.2.246 · Cited by 390 · see citing works
Peptide and protein drug delivery to and into tumors: challenges and solutions
Torchilin, V. P., & Lukyanov, A. N. (2003) · Drug Discovery Today · doi:10.1016/s1359-6446(03)02623-0 · Cited by 363 · see citing works
Tight junction modulation and its relationship to drug delivery
SALAMA, N., EDDINGTON, N., & FASANO, A. (2006) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2006.01.003 · Cited by 357 · see citing works
Emerging Trends in Oral Delivery of Peptide and Protein Drugs
Mahato, R. I., Narang, A. S., Thoma, L. A., & Miller, D. D. (2003) · Critical Reviews in Therapeutic Drug Carrier Systems · doi:10.1615/critrevtherdrugcarriersyst.v20.i23.30 · Cited by 352 · see citing works
Camenisch, G., Alsenz, J., Waterbeemd, H. V. D., & Folkers, G. (1998) · European Journal of Pharmaceutical Sciences · doi:10.1016/s0928-0987(97)10019-7 · Cited by 348 · see citing works
Transmucosal macromolecular drug delivery
Prego, C., García-Fuentes, M., Torres, D., & Alonso, M. J. (2004) · Journal of Controlled Release · doi:10.1016/j.jconrel.2004.07.030 · Cited by 339 · see citing works
Takeuchi, H., Matsui, Y., Yamamoto, H., & Kawashimà, Y. (2003) · Journal of Controlled Release · doi:10.1016/s0168-3659(02)00411-x · Cited by 289 · see citing works
Targeted prodrug design to optimize drug delivery
Han, H.-K., & Amidon, G. L. (2000) · AAPS PharmSci · doi:10.1208/ps020106 · Cited by 277 · see citing works
Tseng, Y., Liu, J., & Hong, R. (2002) · Molecular Pharmacology · doi:10.1124/mol.62.4.864 · Cited by 241 · see citing works
Pharmacological activity of peroral chitosan–insulin nanoparticles in diabetic rats
Ma, Z., Lim, T. M., & Lim, L. Y. (2005) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2004.12.025 · Cited by 231 · see citing works
Enhancing paracellular permeability by modulating epithelial tight junctions
Ward, P., Tippin, T. K., & Thakker, D. R. (2000) · Pharmaceutical Science & Technology Today · doi:10.1016/s1461-5347(00)00302-3 · Cited by 227 · see citing works
Keynote review: intestinal Peyer's patch M cells and oral vaccine targeting
Brayden, D. J., Jepson, M. A., & Baird, A. W. (2005) · Drug Discovery Today · doi:10.1016/s1359-6446(05)03536-1 · Cited by 224 · see citing works
Kawashima, Y., Yamamoto, H., 洋文, 竹., & Kuno, Y. (2000) · Pharmaceutical Development and Technology · doi:10.1081/pdt-100100522 · Cited by 215 · see citing works
Basu, A., Yang, K., Wang, M., Liu, S., Chintala, R., Palm, T., Zhao, H., Peng, P., Wu, D., Zhang, Z., et al. (2006) · Bioconjugate Chemistry · doi:10.1021/bc050322y · Cited by 213 · see citing works
Chances and pitfalls of cell penetrating peptides for cellular drug delivery
Tréhin, R., & Merkle, H. P. (2004) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2004.02.018 · Cited by 200 · see citing works
Tat-Conjugated PAMAM Dendrimers as Delivery Agents for Antisense and siRNA Oligonucleotides
Kang, H. M., DeLong, R. K., Fisher, M. H., & Juliano, R. L. (2005) · Pharmaceutical Research · doi:10.1007/s11095-005-8330-5 · Cited by 197 · see citing works
Vivès, É. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.09.032 · Cited by 196 · see citing works
Morishita, M., Goto, T., Nakamura, K., Lowman, A. M., Takayama, K., & Peppas, N. A. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.10.029 · Cited by 191 · see citing works
Self-citationGarcía-Fuentes, M., Prego, C., Torres, D., & Alonso, M. J. (2005) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2005.02.008 · Cited by 171 · see citing works
Self-assembled “nanocubicle” as a carrier for peroral insulin delivery
Chung, H. J., Kim, J. H., Um, J. Y., Kwon, I. C., & Jeong, S. Y. (2002) · Diabetologia · doi:10.1007/s00125-001-0751-z · Cited by 166 · see citing works
Shakweh, M., Besnard, M., Nicolas, V., & Fattal, E. (2005) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2005.04.006 · Cited by 161 · see citing works
Development of acrylic-based copolymers for oral insulin delivery
Foss, A. C., Goto, T., Morishita, M., & Peppas, N. A. (2003) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(03)00145-0 · Cited by 161 · see citing works
Self-citationFlux Measurements across Caco-2 Monolayers May Predict Transport in Human Large Intestinal Tissue
Rubas, W., Cromwell, M. E. M., Shahrokh, Z., Villagran, J., Nguyen, T. N. Q., Wellton, M., Nguyen, T.-H., & Mrsny, R. J. (1996) · Journal of Pharmaceutical Sciences · doi:10.1021/js950267+ · Cited by 160 · see citing works
Salamat‐Miller, N., & Johnston, T. P. (2005) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2005.01.022 · Cited by 156 · see citing works
Issues in Oral Nanoparticle Drug Carrier Uptake and Targeting
Florence, A. T. (2004) · Journal of drug targeting · doi:10.1080/10611860410001693706 · Cited by 147 · see citing works
MORISHITA, M., Morishita, I., TAKAYAMA, K., Machida, Y., & NAGAI, T. (1993) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.16.68 · Cited by 141 · see citing works
Self-citationReversible lipidization for the oral delivery of salmon calcitonin
Wang, J., Chow, D. D., Heiati, H., & Shen, W. (2003) · Journal of Controlled Release · doi:10.1016/s0168-3659(03)00008-7 · Cited by 125 · see citing works
Insulin-cell penetrating peptide hybrids with improved intestinal absorption efficiency
Liang, J. F., & Yang, V. C.-M. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.07.142 · Cited by 124 · see citing works
Bai, Y., Ann, D. K., & Shen, W. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500062102 · Cited by 123 · see citing works
Damgé, C., Michel, C., Aprahamian, M., et al. (1988) · Diabetes · doi:10.2337/diabetes.37.2.246 · Cited by 123 · see citing works
Enhanced heparan sulfate proteoglycan-mediated uptake of cell-penetrating peptide-modified liposomes
Marty, C., Meylan, C., Schott, H. N., Ballmer‐Hofer, K., & Schwendener, R. A. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4166-0 · Cited by 118 · see citing works
Development and in vivo evaluation of an oral insulin–PEG delivery system
Calceti, P., Salmaso, S., Walker, G. F., & Bernkop‐Schnürch, A. (2004) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2004.03.015 · Cited by 114 · see citing works
Synthesis of Palmitoyl Derivatives of Insulin and Their Biological Activities
Hashimoto, M., Takada, K., Kiso, Y., & Muranishi, S. (1989) · Pharmaceutical Research · doi:10.1023/a:1015992828666 · Cited by 112 · see citing works
Yoo, H. S., & Park, T. G. (2003) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10573 · Cited by 111 · see citing works
Intestinal uptake and biodistribution of novel polymeric micelles after oral administration
Mathot, F., van Beijsterveldt, L., Véronique Préat, A., Brewster, M. E., & Ariën, A. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.11.012 · Cited by 101 · see citing works
Oral Delivery of Proteins: Progress and Prognostication
Shah, R. B., Ahsan, F., & Khan, M. A. (2002) · Critical Reviews in Therapeutic Drug Carrier Systems · doi:10.1615/critrevtherdrugcarriersyst.v19.i2.20 · Cited by 100 · see citing works
Folate receptor mediated intracellular protein delivery using PLL–PEG–FOL conjugate
Kim, S. H., Jeong, J. H., Joe, C. O., & Park, T. G. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.01.006 · Cited by 98 · see citing works
Kipnes, M. S., Dandona, P., Tripathy, D., Still, J., & Kosutic, G. (2003) · Diabetes Care · doi:10.2337/diacare.26.2.421 · Cited by 96 · see citing works
Bendayan, M., Ziv, E., Gingras, D., Ben-Sasson, R., Bar-On, H., & Kidron, M. (1994) · Diabetologia · doi:10.1007/s001250050081 · Cited by 90 · see citing works
Yuan, X., Harada, A., Yamasaki, Y., & Kataoka, K. (2005) · Langmuir · doi:10.1021/la0488811 · Cited by 88 · see citing works
Novel Approaches for Oral Delivery of Macromolecules
Fasano, A. (1998) · Journal of Pharmaceutical Sciences · doi:10.1021/js980076h · Cited by 86 · see citing works
Takenobu, T., Tomizawa, K., Matsushita, M., Li, S. T., Moriwaki, A., Lu, Y., & Matsui, H. (2002) · PubMed · Cited by 85 · see citing works
Datta, K., Sundberg, C. J., Karumanchi, S. A., & Mukhopadhyay, D. (2001) · PubMed · Cited by 78 · see citing works
A novel per‐oral insulin formulation: proof of concept study in non‐diabetic subjects
Kidron, M., Dinh, S. M., Menachem, Y., Abbas, R., Variano, B., Goldberg, M., Arbit, E., & Bar-On, H. (2004) · Diabetic Medicine · doi:10.1111/j.1464-5491.2004.01160.x · Cited by 74 · see citing works
Trojan p16 peptide suppresses pancreatic cancer growth and prolongs survival in mice.
Hosotani, R., Miyamoto, Y., Fujimoto, K., Doi, R., Otaka, A., Fujii, N., & Imamura, M. (2002) · PubMed · Cited by 67 · see citing works
Aoki, Y., Morishita, M., Asai, K., Akikusa, B., Hosoda, S., & Takayama, K. (2005) · Pharmaceutical Research · doi:10.1007/s11095-005-6137-z · Cited by 66 · see citing works
Self-citationUse of Targeting Agents to Increase Uptake and Localization of Drugs to the Intestinal Epithelium
Russell-Jones, G. J. (2004) · Journal of drug targeting · doi:10.1080/10611860410001693760 · Cited by 66 · see citing works
Optimized chemical structure of nanoparticles as carriers for oral delivery of salmon calcitonin
Sakuma, S., Suzuki, N., Sudo, R., Hiwatari, K., Kishida, A., & Akashi, M. (2002) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(02)00113-8 · Cited by 63 · see citing works
Intracellular delivery of antibodies using TAT fusion protein A
Mie, M., Takahashi, F., Funabashi, H., Yanagida, Y., Aizawa, M., & Kobatake, E. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.09.071 · Cited by 61 · see citing works
Prodrug strategies to enhance the intestinal absorption of peptides
Gangwar, S., Pauletti, G. M., Wang, B., Siahaan, T. J., Stella, V. J., & Borchardt, R. T. (1997) · Drug Discovery Today · doi:10.1016/s1359-6446(97)01011-8 · Cited by 50 · see citing works
BIOADHESIVE POLYMER SYSTEMS FOR PEPTIDE DELIVERY
Junginger, H. E. (1990) · Acta pharmaceutica technologica · Cited by 50 · see citing works
竹信, 俊. (2003) · Institutional Repositories DataBase (IRDB) · Cited by 44 · see citing works
Novel Mucosal Insulin Delivery Systems Based on Fusogenic Liposomes
Goto, T., Morishita, M., Nishimura, K., Nakanishi, M., Kato, A., Ehara, J., & Takayama, K. (2005) · Pharmaceutical Research · doi:10.1007/s11095-005-9175-7 · Cited by 42 · see citing works
Self-citationLim, C.-J., & Shen, W. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.05.001 · Cited by 39 · see citing works
Tozaki, H., Odoriba, T., Iseki, T., Taniguchi, T., Fujita, T., Murakami, M., Muranishi, S., & Yamamoto, A. (1998) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1998.tb04008.x · Cited by 37 · see citing works
Transport of IGF-I across epithelial cell monolayers
Bastian, S. E. P., WALTON, P. E., Ballard, F. J., & Belford, D. A. (1999) · Journal of Endocrinology · doi:10.1677/joe.0.1620361 · Cited by 34 · see citing works
Hichens, M. (1983) · Drug Metabolism Reviews · doi:10.3109/03602538308991382 · Cited by 30 · see citing works
Oral insulin delivery systems based on complexation polymer hydrogels
Morishita, M., Goto, T., Takayama, K., & Peppas, N. A. (2006) · Journal of Drug Delivery Science and Technology · doi:10.1016/s1773-2247(06)50003-6 · Cited by 27 · see citing works
Self-citationMizuma, T., Koyanagi, A., & Awazu, S. (2000) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(00)00051-9 · Cited by 21 · see citing works
Biomembrane Permeability of Peptides: Strategies to Improve Their Mucosal Uptake
Bernkop‐Schnürch, A., & Clausen, A. E. (2002) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557023406007 · Cited by 20 · see citing works
Yen, W.-C., & Lee, V. H. L. (1995) · Journal of Controlled Release · doi:10.1016/0168-3659(95)00055-d · Cited by 20 · see citing works
Flagged first, then by citations
6 of the 82 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies
Mitragotri, S., Burke, P. A., & Langer, R. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4363 · Cited by 1,702 · see citing works
Therapeutic efficacy of nanoparticles and routes of administration
Chenthamara, D., Sadhasivam, S., Ramakrishnan, S. G., Krishnaswamy, S., Essa, M. M., Lin, F., & Qoronfleh, M. W. (2019) · Biomaterials Research · doi:10.1186/s40824-019-0166-x · Cited by 1,073 · see citing works
pH-Responsive Nanoparticles for Drug Delivery
Gao, W., Chan, J. M., & Farokhzad, O. C. (2010) · Molecular Pharmaceutics · doi:10.1021/mp100253e · Cited by 1,044 · see citing works
Emerging Frontiers in Drug Delivery
Tibbitt, M. W., Dahlman, J. E., & Langer, R. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.5b09974 · Cited by 982 · see citing works
Basics and Recent Advances in Peptide and Protein Drug Delivery
Bruno, B. J., Miller, G. D., & Lim, C. S. (2013) · Therapeutic Delivery · doi:10.4155/tde.13.104 · Cited by 760 · see citing works
Non-invasive delivery strategies for biologics
Anselmo, A. C., Gokarn, Y. R., & Mitragotri, S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.183 · Cited by 671 · see citing works
Multifaceted Roles of Disulfide Bonds. Peptides as Therapeutics
Góngora‐Benítez, M., Tulla‐Puche, J., & Alberício, F. (2013) · Chemical Reviews · doi:10.1021/cr400031z · Cited by 658 · see citing works
Effect of the surface modification, size, and shape on cellular uptake of nanoparticles
Salatin, S., Dizaj, S. M., & Khosroushahi, A. Y. (2015) · Cell Biology International · doi:10.1002/cbin.10459 · Cited by 627 · see citing works
Alginate/Chitosan Nanoparticles are Effective for Oral Insulin Delivery
Sarmento, B. F. C. C., Ribeiro, A. J., Veiga, F., Sampaio, P., Neufeld, R., & Ferreira, D. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9367-4 · Cited by 618 · see citing works
The safety of chitosan as a pharmaceutical excipient
Baldrick, P. (2009) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2009.09.015 · Cited by 569 · see citing works
An overview of clinical and commercial impact of drug delivery systems
Anselmo, A. C., & Mitragotri, S. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.03.053 · Cited by 523 · see citing works
Design principles of food gels
Cao, Y., & Mezzenga, R. (2020) · Nature Food · doi:10.1038/s43016-019-0009-x · Cited by 510 · see citing works
pH-sensitive vesicles, polymeric micelles, and nanospheres prepared with polycarboxylates
Felber, A. E., Dufresne, M.-H., & Leroux, J. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.09.006 · Cited by 480 · see citing works
Current challenges in non-invasive insulin delivery systems: A comparative review
Khafagy, E., Morishita, M., Onuki, Y., & Takayama, K. (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.08.019 · Cited by 436 · see citing works
Self-citationCurrent state and challenges in developing oral vaccines
Ramirez, J. E. V., Sharpe, L. A., & Peppas, N. A. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.04.008 · Cited by 410 · see citing works
Self-citationOral delivery of proteins and peptides: Challenges, status quo and future perspectives
Zhu, Q., Chen, Z., Paul, P. K., Lü, Y., Wu, W., & Qi, J. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.04.001 · Cited by 366 · see citing works
Therapeutic applications of hydrogels in oral drug delivery
Sharpe, L. A., Daily, A. M., Horava, S. D., & Peppas, N. A. (2014) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.902047 · Cited by 354 · see citing works
Self-citationProgress in biopharmaceutical development
Kęsik-Brodacka, M. (2017) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.1617 · Cited by 354 · see citing works
Muheem, A., Shakeel, F., Jahangir, M. A., Anwar, M., Mallick, N., Jain, G. K., Warsi, M. H., & Ahmad, F. J. (2014) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2014.06.004 · Cited by 343 · see citing works
Phospholipids and Lipid-Based Formulations in Oral Drug Delivery
Fricker, G., Kromp, T., Wendel, A., Blume, A., Zirkel, J., Rebmann, H., Setzer, C., Quinkert, R., Martin, F. J., & Müller-Goymann, C. C. (2010) · Pharmaceutical Research · doi:10.1007/s11095-010-0130-x · Cited by 327 · see citing works
Drug delivery applications of chitin and chitosan: a review
Parhi, R. (2020) · Environmental Chemistry Letters · doi:10.1007/s10311-020-00963-5 · Cited by 311 · see citing works
Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development
Ovacik, M., & Lin, K. (2018) · Clinical and Translational Science · doi:10.1111/cts.12567 · Cited by 299 · see citing works
Anionic nanoparticles enable the oral delivery of proteins by enhancing intestinal permeability
Lamson, N. G., Berger, A. M., Fein, K. C., & Whitehead, K. A. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0465-5 · Cited by 297 · see citing works
Peptidomimetic therapeutics: scientific approaches and opportunities
Qvit, N., Rubin, S. J. S., Urban, T. J., Mochly‐Rosen, D., & Gross, E. R. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.11.003 · Cited by 276 · see citing works
Oral protein delivery: Current status and future prospect
Park, K., Kwon, I. C., & Park, K. (2010) · Reactive and Functional Polymers · doi:10.1016/j.reactfunctpolym.2010.10.002 · Cited by 266 · see citing works
Fan, J., Li, Z.-H., Liu, X., Zheng, D., Chen, Y., & Zhang, X. (2018) · Nano Letters · doi:10.1021/acs.nanolett.7b05323 · Cited by 264 · see citing works
Oral Bioavailability of Insulin Contained in Polysaccharide Nanoparticles
Sarmento, B. F. C. C., Ribeiro, A. J., Veiga, F., Ferreira, D., & Neufeld, R. J. (2007) · Biomacromolecules · doi:10.1021/bm0703923 · Cited by 260 · see citing works
Antimicrobial peptides – Advances in development of therapeutic applications
Luong, H. X., Tùng, T. T., & Tran, T. H. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118407 · Cited by 259 · see citing works
Niu, M., Lü, Y., Hovgaard, L., Guan, P., Tan, Y., Lian, R., Qi, J., & Wu, W. (2012) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2012.02.009 · Cited by 247 · see citing works
Oral Delivery of Biologics for Precision Medicine
Durán‐Lobato, M., Niu, Z., & Alonso, M. J. (2019) · Advanced Materials · doi:10.1002/adma.201901935 · Cited by 247 · see citing works
Polymer-based nanoparticles for oral insulin delivery: Revisited approaches
Fonte, P., Araújo, F., Silva, C., Pereira, C., Reis, S., Santos, H. A., & Sarmento, B. F. C. C. (2015) · Biotechnology Advances · doi:10.1016/j.biotechadv.2015.02.010 · Cited by 243 · see citing works
Subcutaneous delivery of monoclonal antibodies: How do we get there?
Viola, M., Sequeira, J. A. D., Seiça, R. M. F., Veiga, F., Serra, J. P., Paiva‐Santos, A. C., & Ribeiro, A. J. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.08.001 · Cited by 238 · see citing works
Yuan, H., Chen, C., Chai, G., Du, Y., & Hu, F. (2013) · Molecular Pharmaceutics · doi:10.1021/mp300649z · Cited by 234 · see citing works
In vitro and in vivo delivery of therapeutic proteins using cell penetrating peptides
Bolhassani, A., Jafarzade, B. S., & Mardani, G. (2016) · Peptides · doi:10.1016/j.peptides.2016.11.011 · Cited by 234 · see citing works
Medina, R. A., Goeger, D. E., Hills, P., Mooberry, S. L., Huang, N., Romero, L. I., Ortega-Barría, E., Gerwick, W. H., & McPhail, K. L. (2008) · Journal of the American Chemical Society · doi:10.1021/ja801383f · Cited by 231 · see citing works
Clinical translation of long-acting drug delivery formulations
Li, W., Tang, J. T., Lee, D., Tice, T. R., Schwendeman, S. P., & Prausnitz, M. R. (2022) · Nature Reviews Materials · doi:10.1038/s41578-021-00405-w · Cited by 230 · see citing works
Expert opinion: Responsive polymer nanoparticles in cancer therapy
Liechty, W. B., & Peppas, N. A. (2011) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2011.08.004 · Cited by 226 · see citing works
Self-citationLopes, M., Shrestha, N., Correia, A., Shahbazi, M., Sarmento, B. F. C. C., Hirvonen, J. J., Veiga, F., Seiça, R. M. F., Ribeiro, A. J., & Santos, H. A. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.04.012 · Cited by 208 · see citing works
Cell penetrating peptides: the potent multi-cargo intracellular carriers
Kardani, K., Milani, A., Shabani, S. H., & Bolhassani, A. (2019) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2019.1676720 · Cited by 199 · see citing works
Granhall, C., Donsmark, M., Blicher, T. M., Golor, G., Søndergaard, F. L., Thomsen, M., & Bækdal, T. A. (2019) · Clinical Pharmacokinetics · doi:10.1007/s40262-018-0728-4 · Cited by 190 · see citing works
Ouyang, J., Deng, B., Zou, B., Li, Y., Bu, Q., Tian, Y., Chen, M., Chen, W., Kong, N., Chen, T., et al. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c02179 · Cited by 185 · see citing works
Mucoadhesive beads of gellan gum/pectin intended to controlled delivery of drugs
Prezotti, F. G., Cury, B. S. F., & Evangelista, R. C. (2014) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2014.07.021 · Cited by 180 · see citing works
Usefulness of cell-penetrating peptides to improve intestinal insulin absorption
Kamei, N., Morishita, M., Eda, Y., Ida, N., Nishio, R., & Takayama, K. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.08.001 · Cited by 177 · see citing works
Self-citationOral biodrug delivery using cell-penetrating peptide
Khafagy, E., & Morishita, M. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.12.014 · Cited by 173 · see citing works
Self-citationOral insulin delivery: existing barriers and current counter-strategies
Gedawy, A., Martinez, J., Al‐Salami, H., & Dass, C. R. (2017) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.12852 · Cited by 174 · see citing works
Diverse approaches for the enhancement of oral drug bioavailability
Fasinu, P. S., Pillay, V., Ndesendo, V. M. K., du Toit, L. C., & Choonara, Y. E. (2011) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.750 · Cited by 167 · see citing works
Leveraging Physiology for Precision Drug Delivery
Sun, W., Hu, Q., Ji, W., Wright, G., & Gu, Z. (2017) · Physiological Reviews · doi:10.1152/physrev.00015.2016 · Cited by 169 · see citing works
Phage display as a technology delivering on the promise of peptide drug discovery
Hamzeh‐Mivehroud, M., Alizadeh, A. A., Morris, M. B., Church, W. B., & Dastmalchi, S. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2013.09.001 · Cited by 163 · see citing works
Orally Active Peptides: Is There a Magic Bullet?
Räder, A. F. B., Weinmüller, M., Reichart, F., Schumacher‐Klinger, A., Merzbach, S., Gilon, C., Hoffman, A., & Kessler, H. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201807298 · Cited by 163 · see citing works
Wu, W., Niu, M., Lü, Y., & Hovgaard, L. (2011) · International Journal of Nanomedicine · doi:10.2147/ijn.s19917 · Cited by 159 · see citing works
Kirkby, M., Hutton, A. R. J., & Donnelly, R. F. (2020) · Pharmaceutical Research · doi:10.1007/s11095-020-02844-6 · Cited by 156 · see citing works
Oral peptide delivery: Translational challenges due to physiological effects
Tyagi, P., Pechenov, S., & Subramony, J. A. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.08.032 · Cited by 154 · see citing works
Solid lipid nanoparticles for enhanced oral absorption: A review
Salah, E., Abouelfetouh, M. M., Pan, Y., Chen, D., & Xie, S. (2020) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2020.111305 · Cited by 153 · see citing works
Nielsen, E. J. B., Yoshida, S., Kamei, N., Iwamae, R., Khafagy, E., Olsen, J., Rahbek, U. L., Pedersen, B. L., Takayama, K., & Takeda‐Morishita, M. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.06.022 · Cited by 151 · see citing works
Incorporating small molecules or biologics into nanofibers for optimized drug release: A review
Sebe, I., Szabó, P., Kállai-Szabó, B., & Zelkó, R. (2015) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2015.08.054 · Cited by 147 · see citing works
Microfabrication technologies for oral drug delivery
Sant, S., Tao, S. L., Fisher, O. Z., Xu, Q., Peppas, N. A., & Khademhosseini, A. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.11.013 · Cited by 143 · see citing works
Self-citationPEGylated nanomedicines: recent progress and remaining concerns
Vllasaliu, D., Fowler, R., & Stolnik, S. (2014) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.866651 · Cited by 137 · see citing works
Zhang, J., Tang, C., & Yin, C. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.01.079 · Cited by 137 · see citing works
Molecular engineering solutions for therapeutic peptide delivery
Acar, H., Ting, J., Srivastava, S., LaBelle, J. L., & Tirrell, M. (2017) · Chemical Society Reviews · doi:10.1039/c7cs00536a · Cited by 137 · see citing works
Novel Solid Lipid Nanoparticle with Endosomal Escape Function for Oral Delivery of Insulin
Xu, Y., Zheng, Y., Wu, L., Zhu, X., Zhang, Z., & Huang, Y. (2018) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.8b00507 · Cited by 137 · see citing works
Recent progress in design and preparation of glucose-responsive insulin delivery systems
Shen, D., Yu, H., Wang, L., Khan, A., Haq, F., Chen, X., Huang, Q. Y., & Teng, L. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.02.014 · Cited by 136 · see citing works
Cell-penetrating peptides in protein mimicry and cancer therapeutics
Zorko, M., Jones, S., & Langel, Ü. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114044 · Cited by 136 · see citing works
Delivery and therapeutic applications of gene editing technologies ZFNs, TALENs, and CRISPR/Cas9
LaFountaine, J. S., Fathe, K., & Smyth, H. D. C. (2015) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2015.08.029 · Cited by 137 · see citing works
Chitosan nanoparticles: a contribution to nanomedicine
Peniche, H., & Peniche-Covas, C. (2011) · Polymer International · doi:10.1002/pi.3056 · Cited by 132 · see citing works
Plant-Derived Bioactive Peptides: A Treatment to Cure Diabetes
Patil, S. P., Goswami, A., Kalia, K., & Kate, A. S. (2019) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-019-09899-z · Cited by 129 · see citing works
Vesicles from Pluronic/poly(lactic acid) block copolymers as new carriers for oral insulin delivery
Xiong, X. Y., Li, Y. P., Li, Z. L., Zhou, C. L., Tam, K. C., Liu, Z. Y., & Xie, G. X. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.04.004 · Cited by 128 · see citing works
Oral colon delivery of insulin with the aid of functional adjuvants
Maroni, A., Zema, L., Curto, M. D. D., Foppoli, A. A., & Gazzaniga, A. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.10.006 · Cited by 127 · see citing works
Electrostatic Self-Assembled Chitosan-Pectin Nano- and Microparticles for Insulin Delivery
Maciel, V. B. V., Yoshida, C. M. P., Pereira, S., Goycoolea, F. M., & Franco, T. T. (2017) · Molecules · doi:10.3390/molecules22101707 · Cited by 125 · see citing works
Koetting, M. C., Guido, J. F., Gupta, M., Zhang, A., & Peppas, N. A. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.11.023 · Cited by 123 · see citing works
Self-citationFacilitated nanoscale delivery of insulin across intestinal membrane models
Woitiski, C. B., Sarmento, B. F. C. C., Carvalho, R. A., Neufeld, R. J., & Veiga, F. (2011) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2011.04.003 · Cited by 121 · see citing works
Rao, S., & Prestidge, C. A. (2016) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2016.1151872 · Cited by 119 · see citing works
Kamei, N., Morishita, M., & Takayama, K. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2009.02.015 · Cited by 119 · see citing works
Self-citationPharmacological effect of orally delivered insulin facilitated by multilayered stable nanoparticles
Woitiski, C. B., Neufeld, R. J., Veiga, F., Carvalho, R. A., & Figueiredo, I. V. (2010) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2010.08.009 · Cited by 115 · see citing works
Novel strategies in the oral delivery of antidiabetic peptide drugs – Insulin, GLP 1 and its analogs
Ismail, R., & Csóka, I. (2017) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2017.03.015 · Cited by 115 · see citing works
Polymeric nanoparticle system to target activated microglia/macrophages in spinal cord injury
Papa, S., Ferrari, R., Paola, M. D., Rossi, F., Mariani, A., Caron, I., Sammali, E., Peviani, M., Dell’Oro, V., Colombo, C., et al. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.11.001 · Cited by 113 · see citing works
Araújo, F., Shrestha, N., Shahbazi, M., Liu, D., Herranz‐Blanco, B., Mäkilä, E. M., Salonen, J., Hirvonen, J. J., Granja, P. L., Sarmento, B. F. C. C., et al. (2015) · ACS Nano · doi:10.1021/acsnano.5b02762 · Cited by 110 · see citing works
Kang, B.-S., Choi, J., Lee, S., Lee, J.-K., Kim, T., Jang, W. S., Tunsirikongkon, A., Kim, J., & Park, J. (2016) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2016.12.009 · Cited by 109 · see citing works
Novel Platforms for Oral Drug Delivery
Colombo, P., Sonvico, F., Colombo, G., & Bettini, R. (2009) · Pharmaceutical Research · doi:10.1007/s11095-008-9803-0 · Cited by 108 · see citing works
PEG–PLA–PEG block copolymeric nanoparticles for oral immunization against hepatitis B
Jain, A., Goyal, A. K., Mishra, N., Vaidya, B., Mangal, S., & Vyas, S. P. (2009) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2009.12.013 · Cited by 108 · see citing works
Potroz, M. G., Mundargi, R. C., Gillissen, J. J. J., Tan, E., Meker, S., Park, J. H., Jung, H., Park, S.-H., Cho, D., Bang, S. I., et al. (2017) · Advanced Functional Materials · doi:10.1002/adfm.201700270 · Cited by 107 · see citing works
Antimicrobial peptides are degraded by the cytosolic proteases of human erythrocytes
Starr, C. G., & Wimley, W. C. (2017) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2017.09.008 · Cited by 108 · see citing works
Lipid-based nanosuspensions for oral delivery of peptides, a critical review
Dumont, C., Bourgeois, S., Fessi, H., & Jannin, V. (2018) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2018.02.038 · Cited by 107 · see citing works
Stimuli responsive drug delivery application of polymer and silica in biomedicine
Gulzar, A., Gai, S., Yang, P., Li, C., Ansari, M. B., & Lin, J. (2015) · Journal of Materials Chemistry B · doi:10.1039/c5tb00757g · Cited by 106 · see citing works
Lin, C., & Anseth, K. S. (2009) · Biomacromolecules · doi:10.1021/bm900420f · Cited by 106 · see citing works
Peptides as drug delivery vehicles across biological barriers
Ghosh, D., Peng, X., Leal, J., & Mohanty, R. P. (2017) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-017-0374-0 · Cited by 106 · see citing works
Kim, M. S., Park, S. J., Gu, B. K., & Kim, C. (2012) · Applied Surface Science · doi:10.1016/j.apsusc.2012.01.010 · Cited by 106 · see citing works
Chime, S. A. (2013) · African Journal of Pharmacy and Pharmacology · doi:10.5897/ajppx2013.0004 · Cited by 105 · see citing works
Lee, J., & Lee, K. Y. (2009) · Pharmaceutical Research · doi:10.1007/s11095-009-9884-4 · Cited by 105 · see citing works
How to design the surface of peptide-loaded nanoparticles for efficient oral bioavailability?
Malhaire, H., Gimel, J.-C., Roger, E., Benoît, J., & Lagarce, F. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.03.011 · Cited by 102 · see citing works
Administration strategies for proteins and peptides
Ibraheem, D., Elaı̈ssari, A., & Fessi, H. (2014) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2014.10.059 · Cited by 101 · see citing works
Li, P., Tan, A., Prestidge, C. A., Nielsen, H. M., & Müllertz, A. (2014) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2014.10.039 · Cited by 100 · see citing works
Clinical Pharmacology and Interplay of Immune Checkpoint Agents: A Yin-Yang Balance
Géraud, A., Gougis, P., Vozy, A., Anquetil, C., Allenbach, Y., Romano, E., Funck‐Brentano, E., Moslehi, J. J., Johnson, D. B., & Salem, J. (2020) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-022820-093805 · Cited by 94 · see citing works
Khafagy, E., Morishita, M., Kamei, N., Eda, Y., Ikeno, Y., & Takayama, K. (2009) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2009.07.022 · Cited by 94 · see citing works
Self-citationEffects of the Preparation Process on the Properties of Amorphous Solid Dispersions
Huang, S., & Williams, R. O. (2017) · AAPS PharmSciTech · doi:10.1208/s12249-017-0861-7 · Cited by 93 · see citing works
Local delivery of proteins and the use of self-assembling peptides
Segers, V. F. M., & Lee, R. T. (2007) · Drug Discovery Today · doi:10.1016/j.drudis.2007.05.003 · Cited by 92 · see citing works
Self-emulsifying drug delivery systems in oral (poly)peptide drug delivery
Leonavičiǖtė, G., & Bernkop‐Schnürch, A. (2015) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2015.1068287 · Cited by 90 · see citing works
Sun, H., Meng, F., Cheng, R., Deng, C., & Zhong, Z. (2014) · Acta Biomaterialia · doi:10.1016/j.actbio.2014.01.010 · Cited by 86 · see citing works
Recent insights in the use of nanocarriers for the oral delivery of bioactive proteins and peptides
Batista, P., Castro, P. M., Madureira, A. R., Sarmento, B. F. C. C., & Pintado, M. (2018) · Peptides · doi:10.1016/j.peptides.2018.01.002 · Cited by 86 · see citing works
The future of open- and closed-loop insulin delivery systems
Farmer, T. G., Edgar, T. F., & Peppas, N. A. (2007) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.60.1.0001 · Cited by 86 · see citing works
Self-citationPolyelectrolyte complexes as prospective carriers for the oral delivery of protein therapeutics
Bourganis, V., Karamanidou, T., Kammona, O., & Kiparissides, C. A. (2016) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2016.11.005 · Cited by 84 · see citing works
- Authors
- Morishita, M., & Peppas, N. A.
- Affiliations
- Hoshi University (JP)
- The University of Texas at Austin (US)
- Corresponding author
- Morishita, Mariko
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2006-10
- Volume
- 11
- Issue
- 19-20
- Pages
- 905-910
- ISSN
- 1359-6446 (ISSN-L)
- OpenAlex
- W2055249600
- Cited by
- 515
- References
- 82
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 12 · 2023: 21 · 2022: 21 · 2021: 17 · 2020: 33 · 2019: 34 · 2018: 26 · 2017: 37 · 2016: 35 · 2015: 33 · 2014: 43 · 2013: 40 · 2012: 30
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Discovery Today (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Life Sciences › Agricultural and Biological Sciences › Food Science › Proteins in Food Systems
- Keywords
- oral drug delivery, peptide therapeutics, protein drugs, oral bioavailability, membrane permeability, carrier proteins, bioactivity retention
- MeSH terms
- Administration, Oral, Animals, Humans, Peptides, Proteins, Drug Delivery Systems
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