Advertisement

Advanced Nanostructures for Oral Insulin Delivery

  • Chinnu Sabu
  • K. Pramod
Chapter
Part of the Environmental Chemistry for a Sustainable World book series (ECSW, volume 39)

Abstract

  1. 1.

    Issues: Oral insulin therapy is an efficient approach for the treatment and management of Type I and Type II diabetes. Extensive research has been carried out for oral delivery of insulin. The various physicochemical concerns affecting the permeability and dissolution are physical and chemical barriers, solubility, molecular weight, and partition coefficient. Oral insulin mimics the endogenous pathway of insulin; it suffers from first pass metabolism. The advances in nanomedicine result in a more robust insulin delivery system. The utilization of nanoparticles possesses advantages like access to small areas of cell and small volume determination of the analyte.

     
  2. 2.

    Major Advances: The development of nanotechnology has resulted in a new approach to oral insulin delivery. Certain barriers exist in the mechanism of absorption of insulin which can be overcome by nanostructured insulin delivery. We reviewed the recent advances in nanostructured insulin delivery systems. Liquid crystalline nanoparticles, molecularly imprinted hydrogels, lipid-based carriers, polymeric carriers, iron oxide nanoparticles, gold nanoparticles, and silica nanoparticles are among the advanced oral insulin delivery systems. Nanostructures using the natural polymers like chitosan, dextran, and alginate are also discussed. All the developed system proves to a promising approach in the oral delivery of insulin. Biomimetic molecularly imprinted polymer (MIP) nanoparticles act as a potential form of oral insulin delivery system due to specificity and selectivity of the imprint to the polymer, whereas liquid crystalline nanoparticles act as thermodynamically stable structure in oral insulin delivery. Various nanostructures under development are covered in this chapter.

     

Keywords

Oral insulin Diabetes Nanotechnology Nanoparticles Biomimetic Polymers Chitosan Alginate Liquid crystalline Silica 

Abbreviations

AuNP

gold nanoparticles

DPPC

dipalmitoylphosphatidylcholine

DTPA

diethylenetriaminepentaacetic acid

g-PGA

poly-g-glutamic acid

LSC

lauroyl sulfated chitosan

MBA

N,N-methylenebisacrylamide

MIP

Molecularly imprinted polymer

N-glut-PE

N-glutaryl-phosphatidylethanolamine

PLGA

poly(lactide-co-glycolide)

PLGA-PEG

poly (D, L-lactic-co-glycolic acid)-polyethylene glycol

SLN

solid lipid nanoparticles

TMC

N-trimethyl chitosan chloride

TMC-Cys

trimethyl chitosan-cysteine

References

  1. Agrawal AK, Urimi D, Harde H, Kushwah V, Jain S (2015) Folate appended chitosan nanoparticles augment the stability, bioavailability and efficacy of insulin in diabetic rats following oral administration. RSC Adv 5(127):105179–105193.  https://doi.org/10.1039/C5RA19115CrossRefGoogle Scholar
  2. Agrawal AK, Kumar K, Swarnakar NK, Kushwah V, Jain S (2017) “Liquid crystalline nanoparticles”: rationally designed vehicle to improve stability and therapeutic efficacy of insulin following oral administration. Mol Pharm 14(6):1874–1882.  https://doi.org/10.1021/acs.molpharmaceut.6b01099CrossRefPubMedGoogle Scholar
  3. Ahmad A, Othman L, Zaini A, Chowdhury EH (2012) Oral nano-insulin therapy: current progress on nanoparticle-based devices for intestinal epithelium-targeted insulin delivery. J Nanomed Nanotechnol S4:007.  https://doi.org/10.4172/2157-7439.S4-007CrossRefGoogle Scholar
  4. American Diabetes Association (2010) Diagnosis and classification of diabetes mellitus. Diabetes Care 33(Suppl 1):S62–S69.  https://doi.org/10.2337/dc10-S062CrossRefPubMedCentralGoogle Scholar
  5. Andreani T, Kiill CP, Souza ALR d, Fangueiro JF, Fernandes L, Doktorovová S (2014) Surface engineering of silica nanoparticles for oral insulin delivery: characterization and cell toxicity studies. Colloids Surf B Biointerfaces 123:916–923.  https://doi.org/10.1016/j.colsurfb.2014.10.047CrossRefPubMedGoogle Scholar
  6. Bakhru SH, Furtado S, Morello AP, En M (2013) Oral delivery of proteins by biodegradable nanoparticles. Adv Drug Deliv Rev 65(6):811–821.  https://doi.org/10.1016/j.addr.2013.04.006CrossRefPubMedGoogle Scholar
  7. Balabushevich NG, Vikhoreva GA, Mikhal EV, Larionova NI (2010) Fabrication and properties of pH sensitive nanostructured polyelectrolyte microparticles loaded with insulin. Mosc Univ Chem Bull 65(3):148–153.  https://doi.org/10.3103/S0027131410030089CrossRefGoogle Scholar
  8. Boyd W (1998) Recent advances in laser processing of microelectronic materials and devices. J Phys D Appl Phys 21:S22–S27Google Scholar
  9. Chen HY, Zhang J, Gu YQ (2006) Characterization of target effect of nano-hydrogel by near-infrared fluorescent quantum dots. In: Proceedings of International Symposium on Biophotonics, Nanophotonics and Metamaterials. IEEE, Hangzhou, pp 42–45.  https://doi.org/10.1109/METAMAT.2006.334993CrossRefGoogle Scholar
  10. Chen M, Sonaje K, Chen K, Sung H (2011) A review of the prospects for polymeric nanoparticle platforms in oral insulin delivery. Biomaterials 32(36):9826–9838.  https://doi.org/10.1016/j.biomaterials.2011.08.087CrossRefPubMedGoogle Scholar
  11. Chen MC, Mi FL, Liao ZX, Hsiao CW, Sonaje K, Chung MF, Hsu LW, Sung HW (2012) Recent advances in chitosan-based nanoparticles for oral delivery of macromolecules. Adv Drug Deliv Rev 65(6):865–879.  https://doi.org/10.1016/j.addr.2012.10.010CrossRefPubMedGoogle Scholar
  12. Chen M-C, Mi F-L, Liao Z-X, Hsiao C-W, Sonaje K, Chung M-F (2013) Recent advances in chitosan-based nanoparticles for oral delivery of macromolecules. Adv Drug Deliv Rev 65(6):865–879.  https://doi.org/10.1016/j.addr.2012.10.010CrossRefPubMedGoogle Scholar
  13. Cho H, Oh J, Choo M, Ha J, Park Y, Maeng H (2014) Chondroitin sulfate-capped gold nanoparticles for the oral delivery of insulin. Int J Biol Macromol 63:15–20.  https://doi.org/10.1016/j.ijbiomac.2013.10.026CrossRefPubMedGoogle Scholar
  14. Cui F, Qian F, Zhao Z, Yin L, Tang C, Yin C (2009) Preparation, characterization, and oral delivery of insulin loaded carboxylated chitosan grafted poly(methyl methacrylate) nanoparticles. Biomacromolecules 10(5):1253–1258.  https://doi.org/10.1021/bm900035uCrossRefPubMedGoogle Scholar
  15. Diab R, Jaafar-maalej C, Fessi H, Maincent P (2012) Engineered nanoparticulate drug delivery systems : the next frontier for oral administration ? AAPS J 14(4):688–702.  https://doi.org/10.1208/s12248-012-9377-yCrossRefPubMedPubMedCentralGoogle Scholar
  16. Disanto RM, Subramanian V, Gu Z (2016) Recent advances in nanotechnology for diabetes treatment. Wiley Interdiscip Rev Nanomed Nanobiotechnol 7(4):548–564.  https://doi.org/10.1002/wnan.1329CrossRefGoogle Scholar
  17. Florence AT (2004) Issues in oral nanoparticle drug carrier uptake and targeting. J Drug Target 12(2):65–70.  https://doi.org/10.1080/10611860410001693706CrossRefPubMedGoogle Scholar
  18. Florence AT (2012) “Targeting” nanoparticles: the constraints of physical laws and physical barriers. J Control Release 164(2):115–124.  https://doi.org/10.1016/j.jconrel.2012.03.022CrossRefPubMedGoogle Scholar
  19. Fonte P, Araújo F, Silva C, Pereira C, Reis S, Santos HA, Sarmento B (2015) Polymer-based nanoparticles for oral insulin delivery: revisited approaches. Biotechnol Adv 33(6):1342–1354.  https://doi.org/10.1016/j.biotechadv.2015.02.010CrossRefPubMedGoogle Scholar
  20. Ganeshkumar M, Ponrasu T, Sathishkumar M, Suguna L (2013) Preparation of amphiphilic hollow carbon nanosphere loaded insulin for oral delivery. Colloids Surf B Biointerfaces 103:238–243.  https://doi.org/10.1016/j.colsurfb.2012.10.043CrossRefPubMedGoogle Scholar
  21. Hagan DT (1996) The intestinal uptake of particles and the implications for drug and antigen delivery. J Anat 189(Pt 3):477–482. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1167686/Google Scholar
  22. Hall JB, Dobrovolskaia MA, Patri AK, McNeil SE (2007) Characterization of nanoparticles for therapeutics. Nanomedicine 2(6):789–803.  https://doi.org/10.2217/17435889.2.6.789CrossRefPubMedGoogle Scholar
  23. Hecq J, Amighi K, Goole J (2016) Development and evaluation of insulin-loaded cationic solid lipid nanoparticles for oral delivery. J Drug Deliv Sci Technol 36:192–200.  https://doi.org/10.1016/j.jddst.2016.10.012CrossRefGoogle Scholar
  24. Hosseininasab S, Pashaei-asl R, Khandaghi AA, Tayefi H, Nejati-koshki K (2014) Synthesis, characterization, and in vitro studies of PLGA – PEG nanoparticles for oral insulin delivery. Chem Biol Drug Des 84:307–315.  https://doi.org/10.1111/cbdd.12318CrossRefPubMedGoogle Scholar
  25. Hui-xia L, Press D (2012) Solid lipid nanoparticles modified with stearic acid – octaarginine for oral administration of insulin. Int J Nanomed 7:3333–3339.  https://doi.org/10.2147/IJN.S31711CrossRefGoogle Scholar
  26. Ignatious F, Sun L, Lee C, Baldoni J (2010) Electrospun nanofibers in oral drug delivery. Pharm Res 27(4):576–588CrossRefGoogle Scholar
  27. Iyer H, Khedkar A, Verma M (2010) Oral insulin – a review of current status. Diabetes Obes Metab 12(3):179–185CrossRefGoogle Scholar
  28. Journal AI, Karnoosh-yamchi J, Rahmati-yamchi M, Akbarzadeh A, Davaran S, Reza A, Garnoosh K, Bahmani Z, Ashoori M, Mobasse M (2016) pH sensitive insulin-loaded nanohydrogel increases the effect of oral insulin in diabetic rats. Artif Cells, Nanomed, Biotechnol 1401:1–5.  https://doi.org/10.1080/21691401.2016.1216859CrossRefGoogle Scholar
  29. Kaklotar D, Agrawal P, Abdulla A, Singh RP, Mehata AK, Singh S (2016) Transition from passive to active targeting of oral insulin nanomedicines: enhancement in bioavailability and glycemic control in diabetes. Nanomedicine 11(11):1465–1486.  https://doi.org/10.2217/nnm.16.43CrossRefPubMedGoogle Scholar
  30. Katsuma M, Watanabe S, Kawai H, Takemura S, Sako K (2006) Effects of absorption promoters on insulin absorption through colon-targeted delivery. Int J Pharm 307(2):156–162.  https://doi.org/10.1016/j.ijpharm.2005.09.028CrossRefPubMedGoogle Scholar
  31. Kaushik A, Khan R, Solanki PR, Pandey P, Alam J, Ahmad S (2008) Iron oxide nanoparticles-chitosan composite based glucose biosensor. Biosens Bioelectron 24(4):676–683.  https://doi.org/10.1016/j.bios.2008.06.032CrossRefPubMedGoogle Scholar
  32. Kavimandan NJ, Losi E, Peppas NA (2006) Novel delivery system based on complexation hydrogels as delivery vehicles for insulin–transferrin conjugates. Biomaterials 27(20):3846–3854.  https://doi.org/10.1016/j.biomaterials.2006.02.026CrossRefPubMedGoogle Scholar
  33. Kebede A, Singh AK, Rai PK, Giri NK, Rai AK, Watal G (2013) Controlled synthesis, characterization, and application of iron oxide nanoparticles for oral delivery of insulin. Lasers Med Sci 28(2):579–587.  https://doi.org/10.1007/s10103-012-1106-3CrossRefPubMedGoogle Scholar
  34. Kim H, Jun SH, Koo YK, Cho S, Park Y (2013) Green synthesis and nanotopography of heparin-reduced gold nanoparticles with enhanced anticoagulant activity. J Nanosci Nanotechnol 13(3):2068–2076.  https://doi.org/10.1166/jnn.2013.6906CrossRefPubMedGoogle Scholar
  35. Krauland AH, Guggi D, Bernkop-Schnürch A (2004) Oral insulin delivery: the potential of thiolated chitosan-insulin tablets on non-diabetic rats. J Control Release 95(3):547–555.  https://doi.org/10.1016/j.jconrel.2003.12.017CrossRefPubMedGoogle Scholar
  36. Kumari A, Yadav SK, Yadav SC (2010) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces 75(1):1–18.  https://doi.org/10.1016/j.colsurfb.2009.09.001CrossRefPubMedGoogle Scholar
  37. Lin HS, Chen CT, Liang FA, Kulkarni AR, Lee PW, Chen CH, Sung HY (2007) Novel nanoparticles for oral insulin delivery via the paracellular pathway. Nanotechnology 18(10):105102.  https://doi.org/10.1088/0957-4484/18/10/105102CrossRefGoogle Scholar
  38. Liu Y, Kong M, Feng C, Yang KK, Li Y, Su J (2013) Biocompatibility, cellular uptake and biodistribution of the polymeric amphiphilic nanoparticles as oral drug carriers. Colloids Surf B Biointerfaces 103:345–353.  https://doi.org/10.1016/j.colsurfb.2012.11.012CrossRefPubMedGoogle Scholar
  39. Luo YY, Xiong XY, Tian Y, Li ZL, Gong YC, Luo YY (2016) A review of biodegradable polymeric systems for oral insulin delivery. Drug Deliv 23(6):1882–1891.  https://doi.org/10.3109/10717544.2015.1052863CrossRefPubMedGoogle Scholar
  40. Mahkam M (2011) Synthesis and characterization of pH-sensitive silica nanoparticles for oral-insulin delivery. Curr Drug Deliv 8:607–611.  https://doi.org/10.1002/jccs.201200296CrossRefPubMedGoogle Scholar
  41. Mariano L, Giovanna P, Gennara C, Gaetano G (2013) Nanoaggregates based on new poly-hydroxyethyl-aspartamide copolymers for oral insulin absorption. Mol Pharm 10:1644–1654.  https://doi.org/10.1021/mp300226dCrossRefGoogle Scholar
  42. Matteucci E, Giampietro O, Covolan V, Giustarini D, Fanti P, Rossi R (2018) Insulin administration: present strategies and future directions for a noninvasive (possibly more physiological) delivery. Drug Des Devel Ther 9:3109–3118.  https://doi.org/10.2147/DDDT.S79322CrossRefGoogle Scholar
  43. Minimol PF, Paul W, Sharma CP (2013) PEGylated starch acetate nanoparticles and its potential use for oral insulin delivery. Carbohydr Polym 95(1):1–8.  https://doi.org/10.1016/j.carbpol.2013.02.021CrossRefPubMedGoogle Scholar
  44. Mo R, Jiang T, Di J, Tai W, Gu Z (2014) Emerging micro- and nanotechnology based synthetic approaches for insulin delivery. Chem Soc Rev 43(10):3595–3629.  https://doi.org/10.1039/c3cs60436eCrossRefPubMedGoogle Scholar
  45. Mueller C, Verroken A, Javed Iqbal AB (2011) Thiolated chitosans: in vitro comparison of mucoadhesive properties. J Appl Polym Sci 126:449–456.  https://doi.org/10.1002/app.35622CrossRefGoogle Scholar
  46. Mukhopadhyay P, Sarkar K, Chakraborty M, Bhattacharya S, Mishra R, Kundu PP (2013) Oral insulin delivery by self-assembled chitosan nanoparticles: in vitro and in vivo studies in diabetic animal model. Mater Sci Eng C 33(1):376–382.  https://doi.org/10.1016/j.msec.2012.09.001CrossRefGoogle Scholar
  47. Niu M, Lu Y, Hovgaard L, Guan P, Tan Y, Lian R (2012) Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: the effect of cholate type, particle size and administered dose. Eur J Pharm Biopharm 81:265–272.  https://doi.org/10.1016/j.ejpb.2012.02.009CrossRefPubMedGoogle Scholar
  48. Nur M, Vasiljevic T (2017) Can natural polymers assist in delivering insulin orally ? Int J Biol Macromol 103:889–901.  https://doi.org/10.1016/j.ijbiomac.2017.05.138CrossRefPubMedGoogle Scholar
  49. Park K, Chan I, Park K (2011) Reactive & functional polymers oral protein delivery: current status and future prospect. React Funct Polym 71(3):280–287.  https://doi.org/10.1016/j.reactfunctpolym.2010.10.002CrossRefGoogle Scholar
  50. Paul PK, Alongkot T, Suedee R (2017) Biomimetic insulin-imprinted polymer nanoparticles as a potential oral drug delivery system. Acta Pharma 67:149–168.  https://doi.org/10.2217/17435889.2.6.789CrossRefGoogle Scholar
  51. Plapied L, Duhem N, des Rieux A, Préat V (2011) Fate of polymeric nanocarriers for oral drug delivery. Curr Opin Colloid Interface Sci 16(3):228–237.  https://doi.org/10.1016/j.cocis.2010.12.005CrossRefGoogle Scholar
  52. Prego C, Torres D, Fernandez-Megia E, Novoa-Carballal R, Quiñoá E, Alonso MJ (2006) Chitosan–PEG nanocapsules as new carriers for oral peptide delivery: effect of chitosan pegylation degree. J Control Release 111(3):299–308.  https://doi.org/10.1016/j.jconrel.2005.12.015CrossRefPubMedGoogle Scholar
  53. Pridgen EM, Alexis F, Farokhzad OC (2014) Polymeric nanoparticle technologies for oral drug delivery. Clin Gastroenterol Hepatol 12(10):1605–1610.  https://doi.org/10.1016/j.cgh.2014.06.018CrossRefPubMedPubMedCentralGoogle Scholar
  54. Pridgen EM, Alexis F, Farokhzad OC (2015) Polymeric nanoparticle drug delivery technologies for oral delivery applications. Expert Opin Drug Deliv 12(9):1459–1473.  https://doi.org/10.1517/17425247.2015.1018175CrossRefPubMedPubMedCentralGoogle Scholar
  55. Qian F, Cui F, Ding J, Tang C, Yin C (2006) Chitosan graft copolymer nanoparticles for oral protein drug delivery: preparation and characterization. Biomacromolecules 7(10):2722–2727.  https://doi.org/10.1021/bm060065fCrossRefPubMedGoogle Scholar
  56. Ross SA, Gulve EA, Wang M (2004) Chemistry and biochemistry of type 2 diabetes. Chem Rev 104(3):1255–1282.  https://doi.org/10.1021/cr0204653CrossRefPubMedGoogle Scholar
  57. Sadashiv M, Jen W, Suresh S (2015) Application of polymeric nanoparticles and micelles in insulin oral delivery. J Food Drug Anal 23(3):351–358.  https://doi.org/10.1016/j.jfda.2015.01.007CrossRefGoogle Scholar
  58. Sahiner N, Godbey WT, McPherson GL, John VT (2006) Microgel, nanogel and hydrogel-hydrogel semi-IPN composites for biomedical applications: synthesis and characterization. Colloid Polym Sci 284(10):1121–1129.  https://doi.org/10.1007/s00396-006-1489-4CrossRefGoogle Scholar
  59. Sarmento B, Martins S, Ferreira D, Souto EB (2007) Oral insulin delivery by means of solid lipid nanoparticles. Int J Nanomedicine 2(4):743–749PubMedPubMedCentralGoogle Scholar
  60. Shahbazi MA, Santos HA (2013) Improving oral absorption via drug-loaded nanocarriers: absorption mechanisms, intestinal models and rational fabrication. Curr Drug Metab 14(1):28–56. Available from: http://www.eurekaselect.com/node/105467/articleCrossRefGoogle Scholar
  61. Sharma G, Sharma AR, Nam JS, Doss GPC, Lee SS (2015) Nanoparticle based insulin delivery system: the next generation efficient therapy for type 1 diabetes. J Nanobiotechnol 13(74):1–13.  https://doi.org/10.1186/s12951-015-0136-yCrossRefGoogle Scholar
  62. Shelma R, Sharma CP (2011) Submicroparticles composed of amphiphilic chitosan derivative for oral insulin and curcumin release applications. Colloids Surf B Biointerfaces 88(2):722–728.  https://doi.org/10.1016/j.colsurfb.2011.08.007CrossRefPubMedGoogle Scholar
  63. Shofner JP, Phillips MA, Peppas NA (2010) Cellular evaluation of synthesized insulin/transferrin bioconjugates for oral insulin delivery using intelligent complexation hydrogels. Macromol Biosci 10(3):299–306.  https://doi.org/10.1002/mabi.200900223CrossRefPubMedPubMedCentralGoogle Scholar
  64. Siavashani AZ, Nazarpak MH, Bakhsh FF, Toliyat T, Solati-Hashjin M (2013) Preparation of mesoporous silica nanoparticles for insulin drug delivery. Adv Mater Res 829:251–257.  https://doi.org/10.4028/www.scientific.net/AMR.829.251CrossRefGoogle Scholar
  65. Sonaje K, Lin Y-H, Juang J-H, Wey S-P, Chen C-T, Sung H-W (2009) In vivo evaluation of safety and efficacy of self-assembled nanoparticles for oral insulin delivery. Biomaterials 30(12):2329–2339.  https://doi.org/10.1016/j.biomaterials.2008.12.066CrossRefPubMedGoogle Scholar
  66. Sonia TA, Sharma CP (2012) In vitro evaluation of quaternized polydimethylaminoethylmethacrylate sub-microparticles for oral insulin delivery. J Biomater Appl 28(1):62–73.  https://doi.org/10.1177/0885328212437392CrossRefPubMedGoogle Scholar
  67. Su F-Y, Lin K-J, Sonaje K, Wey S-P, Yen T-C, Ho Y-C, Pandaa N, Chuanga EY, Maiti B, Sung HW (2012) Protease inhibition and absorption enhancement by functional nanoparticles for effective oral insulin delivery. Biomaterials 33(9):2801–2811.  https://doi.org/10.1016/j.biomaterials.2011.12.038CrossRefPubMedGoogle Scholar
  68. Sung HW, Sonaje K, Liao ZX, Hsu LW, Chuang EY (2012) pH-responsive nanoparticles shelled with chitosan for oral delivery of insulin: from mechanism to therapeutic applications. Acc Chem Res 45(4):619–629.  https://doi.org/10.1021/ar200234qCrossRefPubMedGoogle Scholar
  69. Varma MVS, Ashokraj Y, Dey CS, Panchagnula R (2003) P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement. Pharmacol Res 48(4):347–359.  https://doi.org/10.1016/S1043-6618(03)00158-0CrossRefPubMedGoogle Scholar
  70. Verma A, Sharma S, Gupta PK, Singh A, Teja BV, Dwivedi P (2016) Vitamin B12 functionalized layer by layer calcium phosphate nanoparticles: a mucoadhesive and pH responsive carrier for improved oral delivery of insulin. Acta Biomater 31:288–300.  https://doi.org/10.1016/j.actbio.2015.12.017CrossRefPubMedGoogle Scholar
  71. Woitiski CB, Carvalho RA, Ribeiro J, Neufeld RJ, Veiga F (2008) Strategies toward the improved oral delivery of insulin nanoparticles via gastrointestinal uptake and translocation. BioDrugs 22(4):223–237CrossRefGoogle Scholar
  72. Wong TW, Sumiran N (2014) Oral calcium pectinate-insulin nanoparticles: influences of alginate, sodium chloride and Tween 80 on their blood glucose lowering performance. J Pharm Pharmacol 66(5):646–657.  https://doi.org/10.1111/jphp.12192CrossRefPubMedGoogle Scholar
  73. Wu J, Zheng Y, Liu M, Shan W, Zhang Z, Huang Y (2018) Biological and medical applications of materials and interfaces biomimetic virus-like and charge reversible nanoparticles to sequentially overcome mucus and epithelial barriers for oral insulin delivery. ACS Appl Mater Interfaces 10:1–37.  https://doi.org/10.1021/acsami.7b16524CrossRefGoogle Scholar
  74. Xu Y, Zheng Y, Wu L, Zhu X, Zhang Z, Huang Y (2018) A novel solid lipid nanoparticle with endosomal escape function for oral delivery of insulin. ACS Appl Mater Interfaces 10:1–25.  https://doi.org/10.1021/acsami.8b00507CrossRefGoogle Scholar
  75. Yan S, Ajun W (2007) Preparation of nanoparticles composed of chitosan and its derivatives as delivery systems for macromolecules. J Appl Polym Sci 105(2):552–561.  https://doi.org/10.1002/app.26038CrossRefGoogle Scholar
  76. Yeh Y, Creran B, Rotello VM (2012) Gold nanoparticles : preparation, properties and applications. Nanoscale 4:1871–1880.  https://doi.org/10.1039/c1nr11188dCrossRefPubMedGoogle Scholar
  77. Yin L, Ding J, He C, Cui L, Tang C, Yin C (2009) Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery. Biomaterials 30(29):5691–5700.  https://doi.org/10.1016/j.biomaterials.2009.06.055CrossRefPubMedGoogle Scholar
  78. Zaidi SA (2016) Latest trends in molecular imprinted polymer based drug delivery systems. RSC Adv 6(91):88807–88819.  https://doi.org/10.1039/C6RA18911CCrossRefGoogle Scholar
  79. Zhang N, Ping Q, Huang G, Xu W, Cheng Y, Han X (2006) Lectin-modified solid lipid nanoparticles as carriers for oral administration of insulin. Int J Pharm 327(1–2):153–159PubMedGoogle Scholar
  80. Zhang X, Sun M, Zheng A, Cao D, Bi Y, Sun J (2012) Preparation and characterization of insulin-loaded bioadhesive PLGA nanoparticles for oral administration. Eur J Pharm Sci 45(5):632–638.  https://doi.org/10.1016/j.ejps.2012.01.002CrossRefPubMedGoogle Scholar
  81. Zhang ZH, Abbad S, Pan RR, Waddad AY, Hou LL, Lv HX, Zhou JP (2013) N-octyl-N-arginine chitosan micelles as an oral delivery system of insulin. J Biomed Nanotechnol 9(4):601–609.  https://doi.org/10.1166/jbn.2013.1572CrossRefPubMedGoogle Scholar
  82. Zhang L, Zhang Y, Qiu J, Li J, Chen W, Guan Y (2017) Preparation and characterization of hypoglycemic nanoparticles for oral insulin delivery. Biomacromolecules 18(12):4281–4291.  https://doi.org/10.1021/acs.biomac.7b01322CrossRefPubMedGoogle Scholar
  83. Zhu S, Qian F, Zhang Y, Tang C, Yin C (2007) Synthesis and characterization of PEG modified N-trimethylaminoethylmethacrylate chitosan nanoparticles. Eur Polym J 43(6):5046–5055.  https://doi.org/10.1016/j.eurpolymj.2007.03.042CrossRefGoogle Scholar
  84. Zijlstra E, Heinemann L, Plum-mörschel L (2014) Oral insulin reloaded: a structured approach. J Diabetes Sci Technol 8(3):458–465CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.College of Pharmaceutical SciencesGovernment Medical CollegeKozhikodeIndia

Personalised recommendations