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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Cell-Penetrating Peptides as a Potential Drug Delivery System for Effective Treatment of Diabetes

Author(s): Mallikarjuna Korivi, Yue-Wern Huang and Betty R. Liu*

Volume 27, Issue 6, 2021

Published on: 18 October, 2020

Page: [816 - 825] Pages: 10

DOI: 10.2174/1381612826666201019102640

Price: $65

Abstract

Background/Purpose: Type 2 diabetes (T2D) is characterized by hyperglycemia resulting from the body’s inability to produce and/or use insulin. Patients with T2D often have hyperinsulinemia, dyslipidemia, inflammation, and oxidative stress, which then lead to hypertension, chronic kidney disease, cardiovascular disease, and increased risk of morbidity and mortality (9th leading cause globally). Insulin and related pharmacological therapies are widely used to manage T2D, despite their limitations. Efficient drug delivery systems (DDS) that control drug kinetics may decrease side effects, allow for efficient targeting, and increase the bioavailability of drugs to achieve maximum therapeutic benefits. Thus, the development of effective DDS is crucial to beat diabetes.

Methods: Here, we introduced a highly bioavailable vector, cell-penetrating peptides (CPPs), as a powerful DDS to overcome limitations of free drug administration.

Results: CPPs are short peptides that serve as a potent tool for delivering therapeutic agents across cell membranes. Various cargoes, including proteins, DNA, RNA, liposomes, therapeutic molecules, and nanomaterials, generally retain their bioactivity upon entering cells. The mechanisms of CPPs/cargoes intracellular entry are classified into two parts: endocytic pathways and direct membrane translocation. In this article, we focus on the applications of CPPs/therapeutic agents in the treatment of diabetes. Hypoglycemic drugs with CPPs intervention can enhance therapeutic effectiveness, and CPP-mediated drug delivery can facilitate the actions of insulin. Numerous studies indicate that CPPs can effectively deliver insulin, produce synergistic effects with immunosuppressants for successful pancreatic islet xenotransplantation, prolong pharmacokinetics, and retard diabetic nephropathy.

Conclusion: We suggest that CPPs can be a new generation of drug delivery systems for effective treatment and management of diabetes and diabetes-associated complications.

Keywords: Cell-penetrating peptides (CPPs), diabetes, drug delivery system (DDS), hyperglycemia, metabolic syndrome (MetS), type 2 diabetes (T2D).

« Previous Next »
[1]
Mendrick DL, Diehl AM, Topor LS, et al. Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic. Toxicol Sci 2018; 162(1): 36-42.
[http://dx.doi.org/10.1093/toxsci/kfx233] [PMID: 29106690]
[2]
Saklayen MG. The Global Epidemic of the Metabolic Syndrome. Curr Hypertens Rep 2018; 20(2): 12.
[http://dx.doi.org/10.1007/s11906-018-0812-z] [PMID: 29480368]
[3]
Ballantyne CM, Hoogeveen RC, McNeill AM, et al. Metabolic syndrome risk for cardiovascular disease and diabetes in the ARIC study. Int J Obes 2008; 32(Suppl. 2): S21-4.
[http://dx.doi.org/10.1038/ijo.2008.31] [PMID: 18469836]
[4]
Adeghate E, Schattner P, Dunn E. An update on the etiology and epidemiology of diabetes mellitus. Ann N Y Acad Sci 2006; 1084: 1-29.
[http://dx.doi.org/10.1196/annals.1372.029] [PMID: 17151290]
[5]
Lustig RH, Schmidt LA, Brindis CD. Public health: The toxic truth about sugar. Nature 2012; 482(7383): 27-9.
[http://dx.doi.org/10.1038/482027a] [PMID: 22297952]
[6]
Beltrán-Sánchez H, Harhay MO, Harhay MM, McElligott S. Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999-2010. J Am Coll Cardiol 2013; 62(8): 697-703.
[http://dx.doi.org/10.1016/j.jacc.2013.05.064] [PMID: 23810877]
[7]
Ogurtsova K, da Rocha Fernandes JD, Huang Y, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 2017; 128: 40-50.
[http://dx.doi.org/10.1016/j.diabres.2017.03.024] [PMID: 28437734]
[8]
Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: Findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 287(3): 356-9.
[http://dx.doi.org/10.1001/jama.287.3.356] [PMID: 11790215]
[9]
Bonomini F, Rodella LF, Rezzani R. Metabolic syndrome, aging and involvement of oxidative stress. Aging Dis 2015; 6(2): 109-20.
[http://dx.doi.org/10.14336/AD.2014.0305] [PMID: 25821639]
[10]
Kharazmi-Khorassani S, Kharazmi-Khorassani J, Rastegar-Moghadam A, et al. Association of a genetic variant in the angiopoietin-like protein 4 gene with metabolic syndrome. BMC Med Genet 2019; 20(1): 97.
[http://dx.doi.org/10.1186/s12881-019-0825-8] [PMID: 31164103]
[11]
Gusarova V, O’Dushlaine C, Teslovich TM, et al. Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes. Nat Commun 2018; 9(1): 2252.
[http://dx.doi.org/10.1038/s41467-018-04611-z] [PMID: 29899519]
[12]
Haydar S, Grigorescu F, Lautier C, et al. Association of ATF5 Gene with Metabolic Syndrome and Insulin Resistance in Mediterranean Populations. Diabetes 2018.
[http://dx.doi.org/10.2337/db18-2410-PUB]
[13]
Ishizaka N, Ishizaka Y, Toda E, Hashimoto H, Nagai R, Yamakado M. Association between cigarette smoking, metabolic syndrome, and carotid arteriosclerosis in Japanese individuals. Atherosclerosis 2005; 181(2): 381-8.
[http://dx.doi.org/10.1016/j.atherosclerosis.2005.01.026] [PMID: 16039294]
[14]
Bajaj M. Nicotine and insulin resistance: When the smoke clears. Diabetes 2012; 61(12): 3078-80.
[http://dx.doi.org/10.2337/db12-1100] [PMID: 23172960]
[15]
Singh A, Amin H, Garg R, et al. Increased Prevalence of Obesity and Metabolic Syndrome in Patients with Alcoholic Fatty Liver Disease. Dig Dis Sci 2020.
[http://dx.doi.org/10.1007/s10620-020-06056-1] [PMID: 31981110]
[16]
Heiston EM, Eichner NZ, Gilbertson NM, Malin SK. Exercise improves adiposopathy, insulin sensitivity and metabolic syndrome severity independent of intensity. Exp Physiol 2020; 105(4): 632-40.
[http://dx.doi.org/10.1113/EP088158] [PMID: 32020676]
[17]
Boles A, Kandimalla R, Reddy PH. Dynamics of diabetes and obesity: Epidemiological perspective. Biochim Biophys Acta Mol Basis Dis 2017; 1863(5): 1026-36.
[http://dx.doi.org/10.1016/j.bbadis.2017.01.016] [PMID: 28130199]
[18]
Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world--a growing challenge. N Engl J Med 2007; 356(3): 213-5.
[http://dx.doi.org/10.1056/NEJMp068177] [PMID: 17229948]
[19]
Aguilar M, Bhuket T, Torres S, Liu B, Wong RJ. Prevalence of the metabolic syndrome in the United States, 2003-2012. JAMA 2015; 313(19): 1973-4.
[http://dx.doi.org/10.1001/jama.2015.4260] [PMID: 25988468]
[20]
Shi L, Shu XO, Li H, et al. Physical activity, smoking, and alcohol consumption in association with incidence of type 2 diabetes among middle-aged and elderly Chinese men. PLoS One 2013; 8(11): e77919.
[http://dx.doi.org/10.1371/journal.pone.0077919] [PMID: 24223743]
[21]
Liu Y, Ye W, Chen Q, Zhang Y, Kuo CH, Korivi M. Resistance Exercise Intensity is Correlated with Attenuation of HbA1c and Insulin in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health 2019; 16(1)E140
[http://dx.doi.org/10.3390/ijerph16010140] [PMID: 30621076]
[22]
Ramudu SK, Korivi M, Kesireddy N, Chen CY, Kuo CH, Kesireddy SR. Ginger feeding protects against renal oxidative damage caused by alcohol consumption in rats. J Ren Nutr 2011; 21(3): 263-70.
[http://dx.doi.org/10.1053/j.jrn.2010.03.003] [PMID: 20599394]
[23]
Zhang X, Zhang JH, Chen XY, et al. Reactive oxygen species-induced TXNIP drives fructose-mediated hepatic inflammation and lipid accumulation through NLRP3 inflammasome activation. Antioxid Redox Signal 2015; 22(10): 848-70.
[http://dx.doi.org/10.1089/ars.2014.5868] [PMID: 25602171]
[24]
Florez JC. The new type 2 diabetes gene TCF7L2. Curr Opin Clin Nutr Metab Care 2007; 10(4): 391-6.
[http://dx.doi.org/10.1097/MCO.0b013e3281e2c9be] [PMID: 17563454]
[25]
Billings LK, Florez JC. The genetics of type 2 diabetes: What have we learned from GWAS? Ann N Y Acad Sci 2010; 1212: 59-77.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05838.x] [PMID: 21091714]
[26]
Dziewulska A, Dobosz AM, Dobrzyn A. High-Throughput Approaches onto Uncover (Epi)Genomic Architecture of Type 2 Diabetes. Genes (Basel) 2018; 9(8)E374
[http://dx.doi.org/10.3390/genes9080374] [PMID: 30050001]
[27]
Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet 2017; 389(10085): 2239-51.
[http://dx.doi.org/10.1016/S0140-6736(17)30058-2] [PMID: 28190580]
[28]
Pesta DH, Goncalves RLS, Madiraju AK, Strasser B, Sparks LM. Resistance training to improve type 2 diabetes: Working toward a prescription for the future. Nutr Metab (Lond) 2017; 14: 24.
[http://dx.doi.org/10.1186/s12986-017-0173-7] [PMID: 28270856]
[29]
Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol 2018; 14(2): 88-98.
[http://dx.doi.org/10.1038/nrendo.2017.151] [PMID: 29219149]
[30]
WHO. Global Reports on Diabetes 2016. Available from: http://apps.who.int/iris/bitstream/10665/204871/204871/9789241565257_eng.pdf
[31]
Colberg SR, Sigal RJ, Yardley JE, et al. Physical Activity/Exercise and Diabetes: A Position Statement of the American Diabetes Association. Diabetes Care 2016; 39(11): 2065-79.
[http://dx.doi.org/10.2337/dc16-1728] [PMID: 27926890]
[32]
Hemmingsen B, Gimenez-Perez G, Mauricio D, Roqué I Figuls M, Metzendorf MI, Richter B. Diet, physical activity or both for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus. Cochrane Database Syst Rev 2017; 12CD003054
[http://dx.doi.org/10.1002/14651858.CD003054.pub4] [PMID: 29205264]
[33]
Chaudhury A, Duvoor C, Reddy Dendi VS, et al. Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management. Front Endocrinol (Lausanne) 2017; 8: 6.
[http://dx.doi.org/10.3389/fendo.2017.00006] [PMID: 28167928]
[34]
Dong X. Current Strategies for Brain Drug Delivery. Theranostics 2018; 8(6): 1481-93.
[http://dx.doi.org/10.7150/thno.21254] [PMID: 29556336]
[35]
Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 2013; 65(1): 36-48.
[http://dx.doi.org/10.1016/j.addr.2012.09.037] [PMID: 23036225]
[36]
Castle J, Feinstein SB. Drug and Gene Delivery using Sonoporation for Cardiovascular Disease. Adv Exp Med Biol 2016; 880: 331-8.
[http://dx.doi.org/10.1007/978-3-319-22536-4_18] [PMID: 26486346]
[37]
Tiwari G, Tiwari R, Sriwastawa B, et al. Drug delivery systems: An updated review. Int J Pharm Investig 2012; 2(1): 2-11.
[http://dx.doi.org/10.4103/2230-973X.96920] [PMID: 23071954]
[38]
Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science 2004; 303(5665): 1818-22.
[http://dx.doi.org/10.1126/science.1095833] [PMID: 15031496]
[39]
Bajracharya R, Song JG, Back SY, Han HK. Recent Advancements in Non-Invasive Formulations for Protein Drug Delivery. Comput Struct Biotechnol J 2019; 17: 1290-308.
[http://dx.doi.org/10.1016/j.csbj.2019.09.004] [PMID: 31921395]
[40]
Lorden ER, Levinson HM, Leong KW. Integration of drug, protein, and gene delivery systems with regenerative medicine. Drug Deliv Transl Res 2015; 5(2): 168-86.
[http://dx.doi.org/10.1007/s13346-013-0165-8] [PMID: 25787742]
[41]
Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine 2015; 10: 975-99.
[http://dx.doi.org/10.2147/IJN.S68861] [PMID: 25678787]
[42]
Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology 2018; 16(1): 71-1.
[http://dx.doi.org/10.1186/s12951-018-0392-8] [PMID: 30231877]
[43]
Zhang Y, Chan HF, Leong KW. Advanced materials and processing for drug delivery: the past and the future. Adv Drug Deliv Rev 2013; 65(1): 104-20.
[http://dx.doi.org/10.1016/j.addr.2012.10.003] [PMID: 23088863]
[44]
Johnstone TC, Suntharalingam K, Lippard SJ. The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs. Chem Rev 2016; 116(5): 3436-86.
[http://dx.doi.org/10.1021/acs.chemrev.5b00597] [PMID: 26865551]
[45]
Zhao MX, Zhu BJ. The Research and Applications of Quantum Dots as Nano-Carriers for Targeted Drug Delivery and Cancer Therapy. Nanoscale Res Lett 2016; 11(1): 207.
[http://dx.doi.org/10.1186/s11671-016-1394-9] [PMID: 27090658]
[46]
Frandsen JL, Ghandehari H. Recombinant protein-based polymers for advanced drug delivery. Chem Soc Rev 2012; 41(7): 2696-706.
[http://dx.doi.org/10.1039/c2cs15303c] [PMID: 22344293]
[47]
Wong CY, Martinez J, Dass CR. Oral delivery of insulin for treatment of diabetes: status quo, challenges and opportunities. J Pharm Pharmacol 2016; 68(9): 1093-108.
[http://dx.doi.org/10.1111/jphp.12607] [PMID: 27364922]
[48]
Chen J, Liu R, Liu C, et al. Progress of Oral Insulin and Related Drug Delivery Systems and their Pharmacokinetics. Curr Drug Metab 2018; 19(10): 863-70.
[http://dx.doi.org/10.2174/1389200219666180523101434] [PMID: 29788884]
[49]
Gedawy A, Martinez J, Al-Salami H, Dass CR. Oral insulin delivery: existing barriers and current counter-strategies. J Pharm Pharmacol 2018; 70(2): 197-213.
[http://dx.doi.org/10.1111/jphp.12852] [PMID: 29193053]
[50]
Kamei N, Shigei C, Hasegawa R, Takeda-Morishita M. Exploration of the key factors for optimizing the in vivo oral delivery of insulin by using a noncovalent strategy with cell-penetrating peptides. Biol Pharm Bull 2018; 41(2): 239-46.
[http://dx.doi.org/10.1248/bpb.b17-00798] [PMID: 29386483]
[51]
Gessner I, Neundorf I. Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy. Int J Mol Sci 2020; 21(7)E2536
[http://dx.doi.org/10.3390/ijms21072536] [PMID: 32268473]
[52]
Frankel AD, Pabo CO. Cellular uptake of the tat protein from human immunodeficiency virus. Cell 1988; 55(6): 1189-93.
[http://dx.doi.org/10.1016/0092-8674(88)90263-2] [PMID: 2849510]
[53]
Green M, Loewenstein PM. Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell 1988; 55(6): 1179-88.
[http://dx.doi.org/10.1016/0092-8674(88)90262-0] [PMID: 2849509]
[54]
Vivès E, Brodin P, Lebleu B. A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J Biol Chem 1997; 272(25): 16010-7.
[http://dx.doi.org/10.1074/jbc.272.25.16010] [PMID: 9188504]
[55]
Liu BR, Huang YW, Aronstam RS, Lee HJ. Comparative mechanisms of protein transduction mediated by cell-penetrating peptides in prokaryotes. J Membr Biol 2015; 248(2): 355-68.
[http://dx.doi.org/10.1007/s00232-015-9777-x] [PMID: 25655108]
[56]
Elliott G, O’Hare P. Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell 1997; 88(2): 223-33.
[http://dx.doi.org/10.1016/S0092-8674(00)81843-7] [PMID: 9008163]
[57]
Gao C, Mao S, Ditzel HJ, et al. A cell-penetrating peptide from a novel pVII-pIX phage-displayed random peptide library. Bioorg Med Chem 2002; 10(12): 4057-65.
[http://dx.doi.org/10.1016/S0968-0896(02)00340-1] [PMID: 12413859]
[58]
Freire JM, Almeida Dias S, Flores L, Veiga AS, Castanho MA. Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides. Bioinformatics 2015; 31(14): 2252-6.
[http://dx.doi.org/10.1093/bioinformatics/btv131] [PMID: 25725499]
[59]
Guidotti G, Brambilla L, Rossi D. Cell-Penetrating Peptides: From Basic Research to Clinics. Trends Pharmacol Sci 2017; 38(4): 406-24.
[http://dx.doi.org/10.1016/j.tips.2017.01.003] [PMID: 28209404]
[60]
Agrawal P, Bhalla S, Usmani SS, et al. CPPsite 2.0: a repository of experimentally validated cell-penetrating peptides. Nucleic Acids Res 2016; 44(D1): D1098-103.
[http://dx.doi.org/10.1093/nar/gkv1266] [PMID: 26586798]
[61]
Gautam A, Chaudhary K, Kumar R, et al. In silico approaches for designing highly effective cell penetrating peptides. J Transl Med 2013; 11: 74.
[http://dx.doi.org/10.1186/1479-5876-11-74] [PMID: 23517638]
[62]
Pandey P, Patel V, George NV, Mallajosyula SS. KELM-CPPpred: Kernel Extreme Learning Machine Based Prediction Model for Cell-Penetrating Peptides. J Proteome Res 2018; 17(9): 3214-22.
[http://dx.doi.org/10.1021/acs.jproteome.8b00322] [PMID: 30032609]
[63]
Borrelli A, Tornesello AL, Tornesello ML, Buonaguro FM. Cell Penetrating Peptides as Molecular Carriers for Anti-Cancer Agents. Molecules 2018; 23(2)E295
[http://dx.doi.org/10.3390/molecules23020295] [PMID: 29385037]
[64]
Jung HE, Oh JE, Lee HK. Cell-Penetrating Mx1 Enhances Anti-Viral Resistance against Mucosal Influenza Viral Infection. Viruses 2019; 11(2)E109
[http://dx.doi.org/10.3390/v11020109] [PMID: 30696001]
[65]
Liu BR, Huang YW, Korivi M, Lo SY, Aronstam RS, Lee HJ. The Primary Mechanism of Cellular Internalization for a Short Cell- Penetrating Peptide as a Nano-Scale Delivery System. Curr Pharm Biotechnol 2017; 18(7): 569-84.
[http://dx.doi.org/10.2174/1389201018666170822125737] [PMID: 28828981]
[66]
Futaki S, Nakase I. Cell-Surface Interactions on Arginine-Rich Cell-Penetrating Peptides Allow for Multiplex Modes of Internalization. Acc Chem Res 2017; 50(10): 2449-56.
[http://dx.doi.org/10.1021/acs.accounts.7b00221] [PMID: 28910080]
[67]
Lee HJ, Huang YW, Chiou SH, Aronstam RS. Polyhistidine facilitates direct membrane translocation of cell-penetrating peptides into cells. Sci Rep 2019; 9(1): 9398.
[http://dx.doi.org/10.1038/s41598-019-45830-8] [PMID: 31253836]
[68]
Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature 2003; 422(6927): 37-44.
[http://dx.doi.org/10.1038/nature01451] [PMID: 12621426]
[69]
Liu BR, Huang YW, Winiarz JG, Chiang HJ, Lee HJ. Intracellular delivery of quantum dots mediated by a histidine- and arginine-rich HR9 cell-penetrating peptide through the direct membrane translocation mechanism. Biomaterials 2011; 32(13): 3520-37.
[http://dx.doi.org/10.1016/j.biomaterials.2011.01.041] [PMID: 21329975]
[70]
Liu BR, Lin MD, Chiang HJ, Lee HJ. Arginine-rich cell-penetrating peptides deliver gene into living human cells. Gene 2012; 505(1): 37-45.
[http://dx.doi.org/10.1016/j.gene.2012.05.053] [PMID: 22669044]
[71]
Liu BR, Liou JS, Huang YW, Aronstam RS, Lee HJ. Intracellular delivery of nanoparticles and DNAs by IR9 cell-penetrating peptides. PLoS One 2013; 8(5): e64205.
[http://dx.doi.org/10.1371/journal.pone.0064205] [PMID: 23724035]
[72]
Liu BR, Lo SY, Liu CC, et al. Endocytic Trafficking of Nanoparticles Delivered by Cell-penetrating Peptides Comprised of Nona-arginine and a Penetration Accelerating Sequence. PLoS One 2013; 8(6): e67100.
[http://dx.doi.org/10.1371/journal.pone.0067100] [PMID: 23840594]
[73]
Liu BR, Huang YW, Chiang HJ, Lee HJ. Cell-penetrating peptide-functionalized quantum dots for intracellular delivery. J Nanosci Nanotechnol 2010; 10(12): 7897-905.
[http://dx.doi.org/10.1166/jnn.2010.3012] [PMID: 21121277]
[74]
Nan YH, Park IS, Hahm KS, Shin SY. Antimicrobial activity, bactericidal mechanism and LPS-neutralizing activity of the cell-penetrating peptide pVEC and its analogs. J Pept Sci 2011; 17(12): 812-7.
[http://dx.doi.org/10.1002/psc.1408] [PMID: 21956793]
[75]
Layek B, Lipp L, Singh J. Cell Penetrating Peptide Conjugated Chitosan for Enhanced Delivery of Nucleic Acid. Int J Mol Sci 2015; 16(12): 28912-30.
[http://dx.doi.org/10.3390/ijms161226142] [PMID: 26690119]
[76]
Duchardt F, Fotin-Mleczek M, Schwarz H, Fischer R, Brock R. A comprehensive model for the cellular uptake of cationic cell-penetrating peptides. Traffic 2007; 8(7): 848-66.
[http://dx.doi.org/10.1111/j.1600-0854.2007.00572.x] [PMID: 17587406]
[77]
Bechara C, Sagan S. Cell-penetrating peptides: 20 years later, where do we stand? FEBS Lett 2013; 587(12): 1693-702.
[http://dx.doi.org/10.1016/j.febslet.2013.04.031] [PMID: 23669356]
[78]
Liu BR, Winiarz JG, Moon JS, et al. Synthesis, characterization and applications of carboxylated and polyethylene-glycolated bifunctionalized InP/ZnS quantum dots in cellular internalization mediated by cell-penetrating peptides. Colloids Surf B Biointerfaces 2013; 111: 162-70.
[http://dx.doi.org/10.1016/j.colsurfb.2013.05.038] [PMID: 23792556]
[79]
Rehmani S, Dixon JE. Oral delivery of anti-diabetes therapeutics using cell penetrating and transcytosing peptide strategies. Peptides 2018; 100: 24-35.
[http://dx.doi.org/10.1016/j.peptides.2017.12.014] [PMID: 29412825]
[80]
Liang JF, Yang VC. Insulin-cell penetrating peptide hybrids with improved intestinal absorption efficiency. Biochem Biophys Res Commun 2005; 335(3): 734-8.
[http://dx.doi.org/10.1016/j.bbrc.2005.07.142] [PMID: 16115469]
[81]
Morishita M, Kamei N, Ehara J, Isowa K, Takayama K. A novel approach using functional peptides for efficient intestinal absorption of insulin. J Control Release 2007; 118(2): 177-84.
[http://dx.doi.org/10.1016/j.jconrel.2006.12.022] [PMID: 17270307]
[82]
Kamei N, Morishita M, Takayama K. Importance of intermolecular interaction on the improvement of intestinal therapeutic peptide/protein absorption using cell-penetrating peptides. J Control Release 2009; 136(3): 179-86.
[http://dx.doi.org/10.1016/j.jconrel.2009.02.015] [PMID: 19250953]
[83]
Zhang Y, Li L, Han M, Hu J, Zhang L. Amphiphilic Lipopeptide-Mediated Transport of Insulin and Cell Membrane Penetration Mechanism. Molecules 2015; 20(12): 21569-83.
[http://dx.doi.org/10.3390/molecules201219771] [PMID: 26633348]
[84]
Kristensen M, Franzyk H, Klausen MT, et al. Penetratin-Mediated Transepithelial Insulin Permeation: Importance of Cationic Residues and pH for Complexation and Permeation. AAPS J 2015; 17(5): 1200-9.
[http://dx.doi.org/10.1208/s12248-015-9747-3] [PMID: 25990963]
[85]
Zhu S, Chen S, Gao Y, et al. Enhanced oral bioavailability of insulin using PLGA nanoparticles co-modified with cell-penetrating peptides and Engrailed secretion peptide (Sec). Drug Deliv 2016; 23(6): 1980-91.
[http://dx.doi.org/10.3109/10717544.2015.1043472] [PMID: 26181841]
[86]
Li L, Yang L, Li M, Zhang L. A cell-penetrating peptide mediated chitosan nanocarriers for improving intestinal insulin delivery. Carbohydr Polym 2017; 174: 182-9.
[http://dx.doi.org/10.1016/j.carbpol.2017.06.061] [PMID: 28821057]
[87]
Liu X, Liu C, Zhang W, Xie C, Wei G, Lu W. Oligoarginine-modified biodegradable nanoparticles improve the intestinal absorption of insulin. Int J Pharm 2013; 448(1): 159-67.
[http://dx.doi.org/10.1016/j.ijpharm.2013.03.033] [PMID: 23538098]
[88]
Shan W, Zhu X, Liu M, 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(3): 2345-56.
[http://dx.doi.org/10.1021/acsnano.5b00028] [PMID: 25658958]
[89]
Daimon Y, Kamei N, Kawakami K, et al. Dependence of Intestinal Absorption Profile of Insulin on Carrier Morphology Composed of β-Cyclodextrin-Grafted Chitosan. Mol Pharm 2016; 13(12): 4034-42.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b00561] [PMID: 27749081]
[90]
Guo F, Ouyang T, Peng T, et al. Enhanced oral absorption of insulin using colon-specific nanoparticles co-modified with amphiphilic chitosan derivatives and cell-penetrating peptides. Biomater Sci 2019; 7(4): 1493-506.
[http://dx.doi.org/10.1039/C8BM01485J] [PMID: 30672923]
[91]
Yang L, Li M, Sun Y, Zhang L. A cell-penetrating peptide conjugated carboxymethyl-β-cyclodextrin to improve intestinal absorption of insulin. Int J Biol Macromol 2018; 111: 685-95.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.01.077] [PMID: 29343452]
[92]
Khafagy S, Morishita M, Isowa K, Imai J, Takayama K. Effect of cell-penetrating peptides on the nasal absorption of insulin. J Control Release 2009; 133(2): 103-8.
[http://dx.doi.org/10.1016/j.jconrel.2008.09.076] [PMID: 18930084]
[93]
Patel LN, Wang J, Kim KJ, Borok Z, Crandall ED, Shen WC. Conjugation with cationic cell-penetrating peptide increases pulmonary absorption of insulin. Mol Pharm 2009; 6(2): 492-503.
[http://dx.doi.org/10.1021/mp800174g] [PMID: 19228019]
[94]
Khafagy S, Morishita M, Ida N, Nishio R, Isowa K, Takayama K. Structural requirements of penetratin absorption enhancement efficiency for insulin delivery. J Control Release 2010; 143(3): 302-10.
[http://dx.doi.org/10.1016/j.jconrel.2010.01.019] [PMID: 20096319]
[95]
Hou YW, Chan MH, Hsu HR, et al. Transdermal delivery of proteins mediated by non-covalently associated arginine-rich intracellular delivery peptides. Exp Dermatol 2007; 16(12): 999-1006.
[http://dx.doi.org/10.1111/j.1600-0625.2007.00622.x] [PMID: 18031459]
[96]
Kamei N, Yamaoka A, Fukuyama Y, Itokazu R, Takeda-Morishita M. Noncovalent Strategy with Cell-Penetrating Peptides to Facilitate the Brain Delivery of Insulin through the Blood-Brain Barrier. Biol Pharm Bull 2018; 41(4): 546-54.
[http://dx.doi.org/10.1248/bpb.b17-00848] [PMID: 29607927]
[97]
Hampe L, Xu C, Harris PWR, et al. Synthetic peptides designed to modulate adiponectin assembly improve obesity-related metabolic disorders. Br J Pharmacol 2017; 174(23): 4478-92.
[http://dx.doi.org/10.1111/bph.14050] [PMID: 28945274]
[98]
Achari AE, Jain SK. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int J Mol Sci 2017; 18(6): 1321.
[http://dx.doi.org/10.3390/ijms18061321] [PMID: 28635626]
[99]
Radjainia M, Huang B, Bai B, et al. A highly conserved tryptophan in the N-terminal variable domain regulates disulfide bond formation and oligomeric assembly of adiponectin. FEBS J 2012; 279(14): 2495-507.
[http://dx.doi.org/10.1111/j.1742-4658.2012.08630.x] [PMID: 22583869]
[100]
Kim MJ, Hwang YH, Kim YH, Lee DY. Immunomodulation of cell-penetrating tat-metallothionein for successful outcome of xenotransplanted pancreatic islet. J Drug Target 2017; 25(4): 350-9.
[http://dx.doi.org/10.1080/1061186X.2016.1258704] [PMID: 27829285]
[101]
Chai Z, Wu T, Dai A, et al. Targeting the CDA1/CDA1BP1 Axis Retards Renal Fibrosis in Experimental Diabetic Nephropathy. Diabetes 2019; 68(2): 395-408.
[http://dx.doi.org/10.2337/db18-0712] [PMID: 30425061]
[102]
Lönn P, Dowdy SF. Cationic PTD/CPP-mediated macromolecular delivery: charging into the cell. Expert Opin Drug Deliv 2015; 12(10): 1627-36.
[http://dx.doi.org/10.1517/17425247.2015.1046431] [PMID: 25994800]
[103]
El Zaoui I, Touchard E, Berdugo M, et al. Subconjunctival injection of XG-102, a c-Jun N-terminal kinase inhibitor peptide, in the treatment of endotoxin-induced uveitis in rats. J Ocul Pharmacol Ther 2015; 31(1): 17-24.
[http://dx.doi.org/10.1089/jop.2014.0019] [PMID: 25313830]
[104]
Kilk K, Mahlapuu R, Soomets U, Langel U. Analysis of in vitro toxicity of five cell-penetrating peptides by metabolic profiling. Toxicology 2009; 265(3): 87-95.
[http://dx.doi.org/10.1016/j.tox.2009.09.016] [PMID: 19799958]

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