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Review

miRNAs in Gastrointestinal Diseases: Can We Effectively Deliver RNA-based Therapeutics orally?

ORCID Icon, & ORCID Icon
Pages 2873-2889 | Received 02 May 2019, Accepted 20 Sep 2019, Published online: 18 Nov 2019

References

  • Labatut AE , MattheolabakisG. Non-viral based miR delivery and recent developments. Eur. J. Pharm. Biopharm.128, 82–90 (2018).
  • Bader AG , BrownD , StoudemireJ , LammersP. Developing therapeutic microRNAs for cancer. Gene Ther.18(12), 1121–1126 (2011).
  • Raisch J , Darfeuille-MichaudA , NguyenHT. Role of microRNAs in the immune system, inflammation and cancer. World J. Gastroenterol.19(20), 2985–2996 (2013).
  • Guo W , ChenW , YuW , HuangW , DengW. Small interfering RNA-based molecular therapy of cancers. Chin. J. Cancer32(9), 488–493 (2013).
  • Drury RE , O'ConnorD , PollardAJ. The clinical application of microRNAs in infectious disease. Front. Immunol.8, 1182 (2017).
  • Rettig GR , BehlkeMA. Progress toward in vivo use of siRNAs-II. Mol. Ther.20(3), 483–512 (2012).
  • Lam JKW , ChowMYT , ZhangY , LeungSWS. siRNA versus miRNA as therapeutics for gene silencing. Mol. Ther. Nucleic Acids4, e252 (2015).
  • Aleman LM , DoenchJ , SharpPA. Comparison of siRNA-induced off-target RNA and protein effects. RNA13(3), 385–395 (2007).
  • Zhang B , PanX , CobbGP , AndersonTA. Plant microRNA: a small regulatory molecule with big impact. Dev. Biol.289(1), 3–16 (2006).
  • Bartel DP . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell116(2), 281–297 (2004).
  • Baskerville S , BartelDP. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA11(3), 241–247 (2005).
  • Kim YK , KimVN. Processing of intronic microRNAs. EMBO J.26(3), 775–783 (2007).
  • Shenouda SK , AlahariSK. MicroRNA function in cancer: oncogene or a tumor suppressor?Cancer Metastasis Rev.28(3–4), 369–378 (2009).
  • Tahamtan A , Teymoori-RadM , NakstadB , SalimiV. Anti-inflammatory microRNAs and their potential for inflammatory diseases treatment. Front. Immunol.9, 1377 (2018).
  • Christopher AF , KaurRP , KaurG , KaurA , GuptaV , BansalP. MicroRNA therapeutics: discovering novel targets and developing specific therapy. Perspect. Clin. Res.7(2), 68–74 (2016).
  • Yu L , ToddNW , XingLet al. Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int. J. Cancer127(12), 2870–2878 (2010).
  • Beg MS , BrennerAJ , SachdevJet al. Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors. Invest. New Drugs35(2), 180–188 (2017).
  • Shibata C , OtsukaM , KishikawaTet al. Current status of miRNA-targeting therapeutics and preclinical studies against gastroenterological carcinoma. Mol. Cell. Ther.1, 5 (2013).
  • Huang Y . Preclinical and clinical advances of GalNAc-decorated nucleic acid therapeutics. Mol. Ther. Nucleic Acids6, 116–132 (2017).
  • Prieto J , HerraizM , SangroBet al. The promise of gene therapy in gastrointestinal and liver diseases. Gut52(Suppl. 2), ii49–ii54 (2003).
  • Raemdonck K , VandenbrouckeRE , DemeesterJ , SandersNN , DeSmedt SC. Maintaining the silence: reflections on long-term RNAi. Drug Discov. Today13(21–22), 917–931 (2008).
  • Baumann V , WinklerJ. miRNA-based therapies: strategies and delivery platforms for oligonucleotide and non-oligonucleotide agents. Future Med. Chem.6(17), 1967–1984 (2014).
  • Ibrisimovic M , KneidingerD , LionT , KleinR. An adenoviral vector-based expression and delivery system for the inhibition of wild-type adenovirus replication by artificial microRNAs. Antiviral Res.97(1), 10–23 (2013).
  • Silman NJ , FooksAR. Biophysical targeting of adenovirus vectors for gene therapy. Curr. Opin. Mol. Ther.2(5), 524–531 (2000).
  • Nayerossadat N , MaedehT , AliPA. Viral and nonviral delivery systems for gene delivery. Adv. Biomed. Res.1, 27 (2012).
  • Helander HF , FandriksL. Surface area of the digestive tract – revisited. Scand. J. Gastroenterol.49(6), 681–689 (2014).
  • Mattheolabakis G , RigasB , ConstantinidesPP. Nanodelivery strategies in cancer chemotherapy: biological rationale and pharmaceutical perspectives. Nanomedicine (Lond.)7(10), 1577–1590 (2012).
  • Reinholz J , LandfesterK , MailanderV. The challenges of oral drug delivery via nanocarriers. Drug Deliv.25(1), 1694–1705 (2018).
  • Lozier JN , YankaskasJR , RamseyWJ , ChenL , BerschneiderH , MorganRA. Gut epithelial cells as targets for gene therapy of hemophilia. Hum. Gene Ther.8(12), 1481–1490 (1997).
  • Robinson K , LetleyDP , KanekoK. The human stomach in health and disease: infection strategies by Helicobacter pylori. Curr. Top. Microbiol. Immunol.400, 1–26 (2017).
  • Hunt RH , CamilleriM , CroweSEet al. The stomach in health and disease. Gut64(10), 1650–1668 (2015).
  • Liu Y , ZhangY , DongPet al. Digestion of nucleic acids starts in the stomach. Sci. Rep.5, 11936 (2015).
  • Loretz B , FogerF , WerleM , Bernkop-SchnurchA. Oral gene delivery: strategies to improve stability of pDNA towards intestinal digestion. J. Drug Target.14(5), 311–319 (2006).
  • Nishi J , FumotoS , IshiiHet al. Highly stomach-selective gene transfer following gastric serosal surface instillation of naked plasmid DNA in rats. J. Gastroenterol.43(12), 912–919 (2008).
  • Ha X , PengJ , ZhaoHet al. Enhancement of gastric ulcer healing and angiogenesis by hepatocyte growth factor gene mediated by attenuated Salmonella in rats. J. Korean Med. Sci.32(2), 186–194 (2017).
  • Johansson ME . Fast renewal of the distal colonic mucus layers by the surface goblet cells as measured by in vivo labeling of mucin glycoproteins. PLoS ONE7(7), e41009 (2012).
  • Lehr C-M , PoelmaFGJ , JungingerHE , TukkerJJ. An estimate of turnover time of intestinal mucus gel layer in the rat in situ loop. Int. J. Pharm.70(3), 235–240 (1991).
  • Hansson GC . Role of mucus layers in gut infection and inflammation. Curr. Opin. Microbiol.15(1), 57–62 (2012).
  • Lai SK , WangYY , HanesJ. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv. Drug Deliv. Rev.61(2), 158–171 (2009).
  • Pullan RD , ThomasGA , RhodesMet al. Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis. Gut35(3), 353–359 (1994).
  • Henke MO , RatjenF. Mucolytics in cystic fibrosis. Paediatr. Respir. Rev.8(1), 24–29 (2007).
  • O'Neill MJ , BourreL , MelgarS , O'DriscollCM. Intestinal delivery of non-viral gene therapeutics: physiological barriers and preclinical models. Drug Discov. Today16(5–6), 203–218 (2011).
  • Ahluwalia B , MoraesL , MagnussonMK , OhmanL. Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies. Scand. J. Gastroenterol.53(4), 379–389 (2018).
  • Matricon J , BarnichN , ArdidD. Immunopathogenesis of inflammatory bowel disease. Self Nonself1(4), 299–309 (2010).
  • Kuhl AA , ErbenU , KredelLI , SiegmundB. Diversity of intestinal macrophages in inflammatory bowel diseases. Front. Immunol.6, 613 (2015).
  • Thomas S , IzardJ , WalshEet al. The host microbiome regulates and maintains human health: a primer and perspective for non-microbiologists. Cancer Res.77(8), 1783–1812 (2017).
  • Karavolos M , HolbanA. Nanosized drug delivery systems in gastrointestinal targeting: interactions with microbiota. Pharmaceuticals (Basel)9(4), 62 (2016).
  • O'Driscoll CM , Bernkop-SchnurchA , FriedlJD , PreatV , JanninV. Oral delivery of non-viral nucleic acid-based therapeutics – do we have the guts for this?Eur. J. Pharm. Sci.133, 190–204 (2019).
  • McConnell EL , ShortMD , BasitAW. An in vivo comparison of intestinal pH and bacteria as physiological trigger mechanisms for colonic targeting in man. J. Control. Rel.130(2), 154–160 (2008).
  • Nishida A , InoueR , InatomiO , BambaS , NaitoY , AndohA. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin. J. Gastroenterol.11(1), 1–10 (2018).
  • Sheehan D , ShanahanF. The gut microbiota in inflammatory bowel disease. Gastroenterol. Clin. North Am.46(1), 143–154 (2017).
  • Ng R , SongG , RollGR , FrandsenNM , WillenbringH. A microRNA-21 surge facilitates rapid cyclin D1 translation and cell cycle progression in mouse liver regeneration. J. Clin. Invest.122(3), 1097–1108 (2012).
  • Png KJ , HalbergN , YoshidaM , TavazoieSF. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature481(7380), 190–194 (2011).
  • Hossian A , SajibMS , TullarPE , MikelisCM , MattheolabakisG. Multipronged activity of combinatorial miR-143 and miR-506 inhibits lung cancer cell cycle progression and angiogenesis in vitro. Sci. Rep.8(1), 10495 (2018).
  • Su Z , YangZ , XuY , ChenY , YuQ. MicroRNAs in apoptosis, autophagy and necroptosis. Oncotarget6(11), 8474–8490 (2015).
  • Rayner KJ , EsauCC , HussainFNet al. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature478(7369), 404–407 (2011).
  • Runtsch MC , RoundJL , O'ConnellRM. MicroRNAs and the regulation of intestinal homeostasis. Front. Genet.5, 347 (2014).
  • Schaefer JS . MicroRNAs: how many in inflammatory bowel disease?Curr. Opin. Gastroenterol.32(4), 258–266 (2016).
  • Orang AV , BarzegariA. MicroRNAs in colorectal cancer: from diagnosis to targeted therapy. Asian Pac. J. Cancer Prev.15(17), 6989–6999 (2014).
  • Krishna CV , SinghJ , ThangavelC , RattanS. Role of microRNAs in gastrointestinal smooth muscle fibrosis and dysfunction: novel molecular perspectives on the pathophysiology and therapeutic targeting. Am. J. Physiol. Gastrointest. Liver Physiol.310(7), G449–G459 (2016).
  • Biton M , LevinA , SlyperMet al. Epithelial microRNAs regulate gut mucosal immunity via epithelium–T cell crosstalk. Nature Immunol.12, 239 (2011).
  • Fasseu M , TretonX , GuichardCet al. Identification of restricted subsets of mature microRNA abnormally expressed in inactive colonic mucosa of patients with inflammatory bowel disease. PLoS ONE5(10), e13160 (2010).
  • Ma F , XuS , LiuXet al. The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-γ. Nat. Immunol.12(9), 861–869 (2011).
  • Sasaki T , HiwatashiN , YamazakiH , NoguchiM , ToyotaT. The role of interferon γ in the pathogenesis of Crohn's disease. Gastroenterol. Jpn27(1), 29–36 (1992).
  • Ito R , Shin-YaM , KishidaTet al. Interferon-γ is causatively involved in experimental inflammatory bowel disease in mice. Clin. Exp. Immunol.146(2), 330–338 (2006).
  • Palmieri O , CreanzaTM , BossaFet al. Functional implications of microRNAs in Crohn's disease revealed by integrating microRNA and messenger RNA expression profiling. Int. J. Mol. Sci.18(7), 1580 (2017).
  • Cheng X , ZhangX , SuJet al. miR-19b downregulates intestinal SOCS3 to reduce intestinal inflammation in Crohn's disease. Sci. Rep.5, 10397 (2015).
  • Parzanese I , QehajajD , PatrinicolaFet al. Celiac disease: from pathophysiology to treatment. World J. Gastrointest. Pathophysiol.8(2), 27–38 (2017).
  • Capuano M , IaffaldanoL , TintoNet al. MicroRNA-449a overexpression, reduced NOTCH1 signals and scarce goblet cells characterize the small intestine of celiac patients. PLoS ONE6(12), e29094 (2011).
  • Ludwig K , FassanM , MescoliCet al. PDCD4/miR-21 dysregulation in inflammatory bowel disease-associated carcinogenesis. Virchows Arch.462(1), 57–63 (2013).
  • Duan J , ZhangH , QuYet al. Onco-miR-130 promotes cell proliferation and migration by targeting TGFβR2 in gastric cancer. Oncotarget7(28), 44522–44533 (2016).
  • Wu J , LiG , YaoY , WangZ , SunW , WangJ. MicroRNA-421 is a new potential diagnosis biomarker with higher sensitivity and specificity than carcinoembryonic antigen and cancer antigen 125 in gastric cancer. Biomarkers20(1), 58–63 (2015).
  • Netz U , CarterJ , EichenbergerMRet al. Plasma microRNA profile differentiates Crohn's colitis from ulcerative colitis. Inflamm. Bowel Dis.24(1), 159–165 (2017).
  • Felli C , BaldassarreA , MasottiA. Intestinal and circulating microRNAs in coeliac disease. Int. J. Mol. Sci.18(9), 1907 (2017).
  • Tsai MM , WangCS , TsaiCYet al. Potential diagnostic, prognostic and therapeutic targets of microRNAs in human gastric cancer. Int. J. Mol. Sci.17(6), 945 (2016).
  • Masuda T , HayashiN , KurodaY , ItoS , EguchiH , MimoriK. MicroRNAs as biomarkers in colorectal cancer. Cancers (Basel)9(9), (2017).
  • Lin J , WelkerNC , ZhaoZet al. Novel specific microRNA biomarkers in idiopathic inflammatory bowel disease unrelated to disease activity. Mod. Pathol.27, 602 (2013).
  • Chen Y , GeW , XuLet al. miR-200b is involved in intestinal fibrosis of Crohn's disease. Int. J. Mol. Med.29(4), 601–606 (2012).
  • Lewis A , MehtaS , HannaLNet al. Low serum levels of microRNA-19 are associated with a stricturing Crohn's disease phenotype. Inflamm. Bowel Dis.21(8), 1926–1934 (2015).
  • Nijhuis A , BiancheriP , LewisAet al. In Crohn's disease fibrosis-reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts. Clin. Sci. (Lond.)127(5), 341–350 (2014).
  • Hou J , HuX , ChenBet al. miR-155 targets Est-1 and induces ulcerative colitis via the IL-23/17/6-mediated Th17 pathway. Pathol. Res. Pract.213(10), 1289–1295 (2017).
  • Bian Z , LiL , CuiJet al. Role of miR-150-targeting c-Myb in colonic epithelial disruption during dextran sulphate sodium-induced murine experimental colitis and human ulcerative colitis. J. Pathol.225(4), 544–553 (2011).
  • Coskun M , BjerrumJT , SeidelinJB , TroelsenJT , OlsenJ , NielsenOH. miR-20b, miR-98, miR-125b-*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis. World J. Gastroenterol.19(27), 4289–4299 (2013).
  • Koukos G , PolytarchouC , KaplanJLet al. MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis. Gastroenterology145(4), 842–852 (2013).
  • Chen Y , XiaoY , GeWet al. miR-200b inhibits TGF-β1-induced epithelial–mesenchymal transition and promotes growth of intestinal epithelial cells. Cell Death Dis.4, e541 (2013).
  • Chapman CG , PekowJ. The emerging role of miRNAs in inflammatory bowel disease: a review. Therap. Adv. Gastroenterol.8(1), 4–22 (2015).
  • Koga Y , YasunagaM , TakahashiAet al. MicroRNA expression profiling of exfoliated colonocytes isolated from feces for colorectal cancer screening. Cancer Prev. Res. (Phila.)3(11), 1435–1442 (2010).
  • Huang Z , HuangD , NiS , PengZ , ShengW , DuX. Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int. J. Cancer127(1), 118–126 (2010).
  • Ng EK , ChongWW , JinHet al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut58(10), 1375–1381 (2009).
  • Nakajima G , HayashiK , XiYet al. Non-coding microRNAs hsa-let-7g and hsa-miR-181b are associated with chemoresponse to S-1 in colon cancer. Cancer Genomics Proteomics3(5), 317–324 (2006).
  • Motoyama K , InoueH , TakatsunoYet al. Over- and under-expressed microRNAs in human colorectal cancer. Int. J. Oncol.34(4), 1069–1075 (2009).
  • Slaby O , SvobodaM , FabianPet al. Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology72(5–6), 397–402 (2007).
  • Schetter AJ , LeungSY , SohnJJet al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA299(4), 425–436 (2008).
  • Bandres E , CubedoE , AgirreXet al. Identification by real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol. Cancer5, 29 (2006).
  • Wang CJ , ZhouZG , WangLet al. Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer. Dis. Markers26(1), 27–34 (2009).
  • Kulda V , PestaM , TopolcanOet al. Relevance of miR-21 and miR-143 expression in tissue samples of colorectal carcinoma and its liver metastases. Cancer Genet. Cytogenet.200(2), 154–160 (2010).
  • Schepeler T , ReinertJT , OstenfeldMSet al. Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res.68(15), 6416–6424 (2008).
  • Xia SS , ZhangGJ , LiuZLet al. MicroRNA-22 suppresses the growth, migration and invasion of colorectal cancer cells through a Sp1 negative feedback loop. Oncotarget8(22), 36266–36278 (2017).
  • Yang IP , TsaiHL , MiaoZFet al. Development of a deregulating microRNA panel for the detection of early relapse in postoperative colorectal cancer patients. J. Transl. Med.14(1), 108 (2016).
  • Xiao G , TangH , WeiW , LiJ , JiL , GeJ. Aberrant expression of microRNA-15a and microRNA-16 synergistically associates with tumor progression and prognosis in patients with colorectal cancer. Gastroenterol. Res. Pract.2014, 364549 (2014).
  • Konishi H , IchikawaD , KomatsuSet al. Detection of gastric cancer-associated microRNAs on microRNA microarray comparing pre- and post-operative plasma. Br. J. Cancer106(4), 740–747 (2012).
  • Tsujiura M , IchikawaD , KomatsuSet al. Circulating microRNAs in plasma of patients with gastric cancers. Br. J. Cancer102(7), 1174–1179 (2010).
  • Deng H , GuoY , SongHet al. MicroRNA-195 and microRNA-378 mediate tumor growth suppression by epigenetical regulation in gastric cancer. Gene518(2), 351–359 (2013).
  • Wang M , GuH , QianHet al. miR-17-5p/20a are important markers for gastric cancer and murine double minute 2 participates in their functional regulation. Eur. J. Cancer49(8), 2010–2021 (2013).
  • Wu JG , WangJJ , JiangXet al. MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis. Gastric Cancer18(4), 729–739 (2015).
  • Shi DB , WangYW , XingAYet al. C/EBPα-induced miR-100 expression suppresses tumor metastasis and growth by targeting ZBTB7A in gastric cancer. Cancer Lett.369(2), 376–385 (2015).
  • Sugiyama T , TaniguchiK , MatsuhashiNet al. MiR-133b inhibits growth of human gastric cancer cells by silencing pyruvate kinase muscle-splicer polypyrimidine tract-binding protein 1. Cancer Sci.107(12), 1767–1775 (2016).
  • Zheng B , LiangL , WangCet al. MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer. Clin. Cancer Res.17(24), 7574–7583 (2011).
  • Zhang D , XiaoYF , ZhangJWet al. miR-1182 attenuates gastric cancer proliferation and metastasis by targeting the open reading frame of hTERT. Cancer Lett.360(2), 151–159 (2015).
  • Chen L , LuMH , ZhangDet al. miR-1207-5p and miR-1266 suppress gastric cancer growth and invasion by targeting telomerase reverse transcriptase. Cell Death Dis.5, e1034 (2014).
  • Cui H , WangL , GongPet al. Deregulation between miR-29b/c and DNMT3A is associated with epigenetic silencing of the CDH1 gene, affecting cell migration and invasion in gastric cancer. PLoS ONE10(4), e0123926 (2015).
  • Hao NB , HeYF , LiXQ , WangK , WangRL. The role of miRNA and lncRNA in gastric cancer. Oncotarget8(46), 81572–81582 (2017).
  • Vaira V , RoncoroniL , BarisaniDet al. microRNA profiles in coeliac patients distinguish different clinical phenotypes and are modulated by gliadin peptides in primary duodenal fibroblasts. Clin. Sci. (Lond.)126(6), 417–423 (2014).
  • Chen HX , MarshallJL , NessEet al. A safety and pharmacokinetic study of a mixed-backbone oligonucleotide (GEM231) targeting the type I protein kinase A by two-hour infusions in patients with refractory solid tumors. Clin. Cancer Res.6(4), 1259–1266 (2000).
  • Tortora G , BiancoR , DamianoVet al. Oral antisense that targets protein kinase A cooperates with taxol and inhibits tumor growth, angiogenesis, and growth factor production. Clin. Cancer Res.6(6), 2506–2512 (2000).
  • Ur Rehman Z , HoekstraD , ZuhornIS. Mechanism of polyplex- and lipoplex-mediated delivery of nucleic acids: real-time visualization of transient membrane destabilization without endosomal lysis. ACS Nano7(5), 3767–3777 (2013).
  • Dai X , ChenX , ChenQet al. MicroRNA-193a-3p reduces intestinal inflammation in response to microbiota via down-regulation of colonic PepT1. J. Biol. Chem.290(26), 16099–16115 (2015).
  • Klausner EA , LeongKW. 167. Polyethyleneimines as vehicles for oral gene delivery. Mol. Ther.13, S64–S65 (2006).
  • Laroui H , TheissAL , YanYet al. Functional TNFα gene silencing mediated by polyethyleneimine/TNFα siRNA nanocomplexes in inflamed colon. Biomaterials32(4), 1218–1228 (2011).
  • Dey A , KamatA , NayakSet al. Role of proton balance in formation of self-assembled chitosan nanoparticles. Colloids Surf. B Biointerfaces166, 127–134 (2018).
  • Roy K , MaoH-Q , HuangSK , LeongKW. Oral gene delivery with chitosan–DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat. Med.5, 387 (1999).
  • He C , YinL , TangC , YinC. Multifunctional polymeric nanoparticles for oral delivery of TNF-α siRNA to macrophages. Biomaterials34(11), 2843–2854 (2013).
  • He C , YinL , SongY , TangC , YinC. Optimization of multifunctional chitosan-siRNA nanoparticles for oral delivery applications, targeting TNF-α silencing in rats. Acta Biomater.17, 98–106 (2015).
  • Bernkop-Schnurch A , KrajicekME. Mucoadhesive polymers as platforms for peroral peptide delivery and absorption: synthesis and evaluation of different chitosan–EDTA conjugates. J. Control. Rel.50(1–3), 215–223 (1998).
  • Zhang J , TangC , YinC. Galactosylated trimethyl chitosan-cysteine nanoparticles loaded with Map4k4 siRNA for targeting activated macrophages. Biomaterials34(14), 3667–3677 (2013).
  • He Z , HuY , NieTet al. Size-controlled lipid nanoparticle production using turbulent mixing to enhance oral DNA delivery. Acta Biomater.81, 195–207 (2018).
  • Patil Y , PanyamJ. Polymeric nanoparticles for siRNA delivery and gene silencing. Int. J. Pharm.367(1-2), 195–203 (2009).
  • Howard KA , LiXW , SomavarapuSet al. Formulation of a microparticle carrier for oral polyplex-based DNA vaccines. Biochim. Biophys. Acta1674(2), 149–157 (2004).
  • Kang SH , RevuriV , LeeSJet al. Oral siRNA delivery to treat colorectal liver metastases. ACS Nano11(10), 10417–10429 (2017).
  • Ballarin-Gonzalez B , Dagnaes-HansenF , FentonRAet al. Protection and systemic translocation of siRNA following oral administration of chitosan/siRNA nanoparticles. Mol. Ther. Nucleic Acids2, e76 (2013).
  • He C , YinL , TangC , YinC. Trimethyl chitosan-cysteine nanoparticles for systemic delivery of TNF-α siRNA via oral and intraperitoneal routes. Pharm. Res.30(10), 2596–2606 (2013).
  • Sadio A , GustafssonJK , PereiraBet al. Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and cross the gastric mucus barrier. PLoS ONE9(6), e99449 (2014).
  • Wei W , LvPP , ChenXMet al. Codelivery of mTERT siRNA and paclitaxel by chitosan-based nanoparticles promoted synergistic tumor suppression. Biomaterials34(15), 3912–3923 (2013).
  • Han L , TangC , YinC. Oral delivery of shRNA and siRNA via multifunctional polymeric nanoparticles for synergistic cancer therapy. Biomaterials35(15), 4589–4600 (2014).
  • Kriegel C , AmijiM. Oral TNF-α gene silencing using a polymeric microsphere-based delivery system for the treatment of inflammatory bowel disease. J. Control. Rel.150(1), 77–86 (2011).
  • Kriegel C , AttarwalaH , AmijiM. Multi-compartmental oral delivery systems for nucleic acid therapy in the gastrointestinal tract. Adv. Drug Deliv. Rev.65(6), 891–901 (2013).
  • Xu J , GaneshS , AmijiM. Non-condensing polymeric nanoparticles for targeted gene and siRNA delivery. Int. J. Pharm.427(1), 21–34 (2012).
  • Kriegel C , AmijiMM. Dual TNF-α/cyclin D1 gene silencing with an oral polymeric microparticle system as a novel strategy for the treatment of inflammatory bowel disease. Clin. Transl. Gastroenterol.2, e2 (2011).
  • Iqbal S , DuX , WangJ , LiH , YuanY , WangJ. Surface charge tunable nanoparticles for TNF-α siRNA oral delivery for treating ulcerative colitis. Nano Res.11(5), 2872–2884 (2018).
  • Huang Y , GuoJ , GuiS. Orally targeted galactosylated chitosan poly(lactic-co-glycolic acid) nanoparticles loaded with TNF-α siRNA provide a novel strategy for the experimental treatment of ulcerative colitis. Eur. J. Pharm. Sci.125, 232–243 (2018).
  • Laroui H , ViennoisE , XiaoBet al. Fab'-bearing siRNA TNFα-loaded nanoparticles targeted to colonic macrophages offer an effective therapy for experimental colitis. J. Control. Rel.186, 41–53 (2014).
  • Xiao B , ZhangZ , ViennoisEet al. Combination therapy for ulcerative colitis: orally targeted nanoparticles prevent mucosal damage and relieve inflammation. Theranostics6(12), 2250–2266 (2016).
  • Sahoo N , SahooRK , BiswasN , GuhaA , KuotsuK. Recent advancement of gelatin nanoparticles in drug and vaccine delivery. Int. J. Biol. Macromol.81, 317–331 (2015).
  • Kaul G , AmijiM. Tumor-targeted gene delivery using poly(ethylene glycol)-modified gelatin nanoparticles: in vitro and in vivo studies. Pharm. Res.22(6), 951–961 (2005).
  • Wang H , BoermanOC , SariibrahimogluK , LiY , JansenJA , LeeuwenburghSC. Comparison of micro- vs nanostructured colloidal gelatin gels for sustained delivery of osteogenic proteins: bone morphogenetic protein-2 and alkaline phosphatase. Biomaterials33(33), 8695–8703 (2012).
  • Bhavsar MD , TiwariSB , AmijiMM. Formulation optimization for the nanoparticles-in-microsphere hybrid oral delivery system using factorial design. J. Control. Rel.110(2), 422–430 (2006).
  • Bhavsar MD , AmijiMM. Gastrointestinal distribution and in vivo gene transfection studies with nanoparticles-in-microsphere oral system (NiMOS). J. Control. Rel.119(3), 339–348 (2007).
  • Kommareddy S , AmijiM. Preparation and evaluation of thiol-modified gelatin nanoparticles for intracellular DNA delivery in response to glutathione. Bioconjug. Chem.16(6), 1423–1432 (2005).
  • Elzoghby AO . Gelatin-based nanoparticles as drug and gene delivery systems: reviewing three decades of research. J. Control. Rel.172(3), 1075–1091 (2013).
  • Cui F , ShiK , ZhangL , TaoA , KawashimaY. Biodegradable nanoparticles loaded with insulin-phospholipid complex for oral delivery: preparation, in vitro characterization and in vivo evaluation. J. Control. Rel.114(2), 242–250 (2006).
  • Malathi S , NandhakumarP , PandiyanV , WebsterTJ , BalasubramanianS. Novel PLGA-based nanoparticles for the oral delivery of insulin. Int. J. Nanomedicine10, 2207–2218 (2015).
  • Panyam J , ZhouWZ , PrabhaS , SahooSK , LabhasetwarV. Rapid endo-lysosomal escape of poly(DL-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB J.16(10), 1217–1226 (2002).
  • Kaneko H , BednarekI , WierzbickiAet al. Oral DNA vaccination promotes mucosal and systemic immune responses to HIV envelope glycoprotein. Virology267(1), 8–16 (2000).
  • He XW , WangF , JiangLet al. Induction of mucosal and systemic immune response by single-dose oral immunization with biodegradable microparticles containing DNA encoding HBsAg. J. Gen. Virol.86(Pt 3), 601–610 (2005).
  • Du L , YuZ , PangFet al. Targeted delivery of GP5 antigen of PRRSV to M cells enhances the antigen-specific systemic and mucosal immune responses. Front. Cell. Infect. Microbiol.8, 7 (2018).
  • Tros De Ilarduya C , SunY , DuzgunesN. Gene delivery by lipoplexes and polyplexes. Eur. J. Pharm. Sci.40(3), 159–170 (2010).
  • Rowland RN , WoodleyJF. The stability of liposomes in vitro to pH, bile salts and pancreatic lipase. Biochim. Biophys. Acta620(3), 400–409 (1980).
  • Zhang Y , CristofaroP , SilbermannRet al. Engineering mucosal RNA interference in vivo. Mol. Ther.14(3), 336–342 (2006).
  • Fichera A , GuoY , RomeroL , MichelassiF , ArenasRB. Quantitation of in vivo gene delivery by restriction enzyme PCR generated polymorphism. J. Surg. Res.69(1), 188–192 (1997).
  • Sugimoto K , OgawaA , MizoguchiEet al. IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J. Clin. Invest.118(2), 534–544 (2008).
  • Ball RL , BajajP , WhiteheadKA. Oral delivery of siRNA lipid nanoparticles: fate in the GI tract. Sci. Rep.8(1), 2178 (2018).
  • Whitehead KA , DorkinJR , VegasAJet al. Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity. Nat. Commun.5, 4277 (2014).
  • Ball RL , KnappCM , WhiteheadKA. Lipidoid nanoparticles for siRNA delivery to the intestinal epithelium: in vitro investigations in a Caco-2 model. PLoS ONE10(7), e0133154 (2015).
  • Hussain N , JaitleyV , FlorenceAT. Recent advances in the understanding of uptake of microparticulates across the gastrointestinal lymphatics. Adv. Drug Deliv. Rev.50(1–2), 107–142 (2001).
  • Lamprecht A , SchaferU , LehrCM. Size-dependent bioadhesion of micro- and nanoparticulate carriers to the inflamed colonic mucosa. Pharm. Res.18(6), 788–793 (2001).
  • Wang YY , LaiSK , SukJS , PaceA , ConeR , HanesJ. Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that ‘slip’ through the human mucus barrier. Angew Chem. Int. Ed. Engl.47(50), 9726–9729 (2008).
  • Lai SK , O'HanlonDE , HarroldSet al. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc. Natl Acad. Sci. USA104(5), 1482–1487 (2007).
  • Rejman J , OberleV , ZuhornIS , HoekstraD. Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem. J.377(Pt 1), 159–169 (2004).
  • Kulkarni SA , FengSS. Effects of particle size and surface modification on cellular uptake and biodistribution of polymeric nanoparticles for drug delivery. Pharm. Res.30(10), 2512–2522 (2013).

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