Application of Chitosan in Oral Drug Delivery

  • Reza Baradaran Eftekhari
  • Niloufar Maghsoudnia
  • Shabnam Samimi
  • Farid Abedin DorkooshEmail author


Oral drug delivery is counted as the preferable route of drug administration due to its convenience, safety, and cost-effectiveness. However, many drugs are not good candidates for oral application mainly because of drug degradation within the gastrointestinal system. Overcoming the obstacles for effective oral delivery of drugs is currently one of the chief goals driving drug delivery research. Recently, remarkable advances in drug delivery technology have led to the increase in the use of various carriers for oral drug delivery. Polymers, as one of the most widely utilized tools, have demonstrated a considerable number of benefits of which stable physicochemical properties and cost-effectiveness are the prominent ones. Along with the mentioned features, an ideal polymeric delivery vehicle should be biocompatible and protect the incorporated drug from enzymatic degradation in the gastrointestinal tract. Chitosan has been extensively studied by many researchers, and a massive data is now available upon its distinctive benefits and restrictions as well as its unique characteristics appreciable for oral drug delivery. It is safe, biocompatible, low cost, and readily available. In addition, intrinsic mucoadhesion ability of chitosan urges its use as an oral drug delivery vehicle. The goal of this chapter is to focus on the application of chitosan as an oral delivery carrier for therapeutic molecules and drugs. Current conventional formulations of chitosan are first reviewed, and the related limitations are investigated to lead readers to the next sections in which novel approaches for improved delivery system are explained as fully as possible. Application of chitosan in oral gene and peptide delivery is explained as separate sections since these two areas have been attracting much attention in recent years due to the intrinsic properties of chitosan making it a promising candidate in the areas. Different strategies employed to improve chitosan polymers regarding physicochemical and targeting properties are covered throughout the script. Diverse modification approaches as well as their limitations are explained, exemplified, and illustrated within the body of the chapter. In the end, the future concept of chitosan oral drug delivery is argued followed by a concise summary.


Chitosan Oral delivery Chitosan tablets Chitosan capsules Chitosan beads Chitosan granules Chitosan nanoparticles Oral gene delivery Oral peptides and proteins delivery Chitosan hydrogels 


  1. Abkar M et al (2017) Oral immunization of mice with Omp31-loaded N-trimethyl chitosan nanoparticles induces high protection against Brucella melitensis infection. Int J Nanomedicine 12:8769PubMedPubMedCentralCrossRefGoogle Scholar
  2. Ahmadivand S et al (2017) Oral DNA vaccines based on CS-TPP nanoparticles and alginate microparticles confer high protection against infectious pancreatic necrosis virus (IPNV) infection in trout. Dev Comp Immunol 74:178–189PubMedCrossRefGoogle Scholar
  3. Ahmed M et al (2009) Formulation andIn-vitroevaluation of chitosan films containing tetracycline for the treatment of periodontitis. Asian J Pharm 3(2):113CrossRefGoogle Scholar
  4. Anal AK, Stevens WF (2005) Chitosan–alginate multilayer beads for controlled release of ampicillin. Int J Pharm 290(1–2):45–54PubMedCrossRefGoogle Scholar
  5. Andreas B, Hornof M, Zoidl T (2003) Thiolated polymers–thiomers: modification of chitosan with 2-iminothiolane. Int J Pharm 260:229–237CrossRefGoogle Scholar
  6. Anseth KS, Bowman CN, Brannon-Peppas L (1996) Mechanical properties of hydrogels and their experimental determination. Biomaterials 17:1647–1657PubMedCrossRefGoogle Scholar
  7. Arif M et al (2018) Development of novel pH-sensitive thiolated chitosan/PMLA nanoparticles for amoxicillin delivery to treat helicobacter pylori. Mater Sci Eng C 83:17–24CrossRefGoogle Scholar
  8. Bacon A et al (2000) Carbohydrate biopolymers enhance antibody responses to mucosally delivered vaccine antigens. Infect Immun 68(10):5764–5770PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bayat A et al (2008) Nanoparticles of quaternized chitosan derivatives as a carrier for colon delivery of insulin: ex vivo and in vivo studies. Int J Pharm 356(1–2):259–266PubMedCrossRefGoogle Scholar
  10. Berger J et al (2004a) Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications. Eur J Pharm Biopharm 57(1):19–34PubMedCrossRefGoogle Scholar
  11. Berger J et al (2004b) Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications. Eur J Pharm Biopharm 57(1):35–52PubMedCrossRefGoogle Scholar
  12. Bernkop-Schnürch A (2005) Thiomers: a new generation of mucoadhesive polymers. Adv Drug Deliv Rev 57(11):1569–1582PubMedCrossRefGoogle Scholar
  13. Bernkop-Schnürch A, Brandt U, Clausen A (1999) Synthesis and in vitro evaluation of chitosan-cysteine conjugates. Sci Pharm 67:196–208Google Scholar
  14. Bernkop-Schnürch A, Hornof M, Zoidl T (2003) Thiolated polymers—thiomers: synthesis and in vitro evaluation of chitosan–2-iminothiolane conjugates. Int J Pharm 260(2):229–237PubMedCrossRefGoogle Scholar
  15. Bernkop-Schnürch A, Hornof M, Guggi D (2004) Thiolated chitosans. Eur J Pharm Biopharm 57(1):9–17PubMedCrossRefGoogle Scholar
  16. Bhattarai N, Gunn J, Zhang M (2010) Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Deliv Rev 62(1):83–99CrossRefGoogle Scholar
  17. Biswas S et al (2014) Structure-toxicity relationship of chemically modified chitosan as an Oral protein drug delivery carrier. J Pharm Sci Pharmacol 1(2):131–140CrossRefGoogle Scholar
  18. Biswas S et al (2015) Development and characterization of alginate coated low molecular weight chitosan nanoparticles as new carriers for oral vaccine delivery in mice. Carbohydr Polym 121:403–410PubMedCrossRefGoogle Scholar
  19. Chandy T, Sharma CP (1992) Chitosan beads and granules for oral sustained delivery of nifedipine: in vitro studies. Biomaterials 13(13):949–952PubMedCrossRefGoogle Scholar
  20. Chaudhury A, Das S (2011) Recent advancement of chitosan-based nanoparticles for oral controlled delivery of insulin and other therapeutic agents. AAPS PharmSciTech 12(1):10–20PubMedCrossRefGoogle Scholar
  21. Chellat F et al (2005) Metalloproteinase and cytokine production by THP-1 macrophages following exposure to chitosan-DNA nanoparticles. Biomaterials 26(9):961–970PubMedCrossRefGoogle Scholar
  22. Chen T et al (2003) Enzyme-catalyzed gel formation of gelatin and chitosan: potential for in situ applications. Biomaterials 24(17):2831–2841PubMedCrossRefGoogle Scholar
  23. Cho BC et al (2005) The effect of chitosan bead encapsulating calcium sulfate as an injectable bone substitute on consolidation in the mandibular distraction osteogenesis of a dog model. J Oral Maxillofac Surg 63(12):1753–1764PubMedCrossRefGoogle Scholar
  24. Chu C-H et al (1996) Development of a model for analyzing the swelling rate of ionic gels on the basis of the diffusion of mobile ions: application to the pH-sensitive swelling of a polyelectrolyte complex gel prepared from xanthan and chitosan. Biosci Biotechnol Biochem 60(10):1627–1632CrossRefGoogle Scholar
  25. Clark MA, Jepson MA, Hirst BH (2001) Exploiting M cells for drug and vaccine delivery. Adv Drug Deliv Rev 50(1–2):81–106PubMedCrossRefGoogle Scholar
  26. Cui F et al (2009) Preparation, characterization, and oral delivery of insulin loaded carboxylated chitosan grafted poly (methyl methacrylate) nanoparticles. Biomacromolecules 10(5):1253–1258PubMedCrossRefGoogle Scholar
  27. Danesh-Bahreini MA et al (2011) Nanovaccine for leishmaniasis: preparation of chitosan nanoparticles containing Leishmania superoxide dismutase and evaluation of its immunogenicity in BALB/c mice. Int J Nanomedicine 6:835PubMedPubMedCentralGoogle Scholar
  28. Denkbas EB, Ottenbrite RM (2006) Perspectives on: chitosan drug delivery systems based on their geometries. J Bioact Compat Polym 21:351–368CrossRefGoogle Scholar
  29. Desai MP et al (1996) Gastrointestinal uptake of biodegradable microparticles: effect of particle size. Pharm Res 13(12):1838–1845PubMedCrossRefGoogle Scholar
  30. Desai MP et al (1997) The mechanism of uptake of biodegradable microparticles in Caco-2 cells is size dependent. Pharm Res 14(11):1568–1573PubMedCrossRefGoogle Scholar
  31. Eldridge JH et al (1990) Controlled vaccine release in the gut-associated lymphoid tissues. I. Orally administered biodegradable microspheres target the Peyer’s patches. J Control Release 11(1–3):205–214CrossRefGoogle Scholar
  32. Fan B et al (2016) pH-responsive thiolated chitosan nanoparticles for oral low-molecular weight heparin delivery: in vitro and in vivo evaluation. Drug Deliv 23(1):238–247PubMedCrossRefGoogle Scholar
  33. Fetih G et al (2005) Improvement of absorption enhancing effects of n-dodecyl-β-D-maltopyranoside by its colon-specific delivery using chitosan capsules. Int J Pharm 293(1–2):127–135PubMedCrossRefGoogle Scholar
  34. Gades MD, Stern JS (2005) Chitosan supplementation and fat absorption in men and women. J Am Diet Assoc 105(1):72–77PubMedCrossRefGoogle Scholar
  35. Gao P et al (2016) Chitosan based nanoparticles as protein carriers for efficient oral antigen delivery. Int J Biol Macromol 91:716–723PubMedCrossRefGoogle Scholar
  36. Gavhane YN, Yadav AV (2013) Improvement in physicochemical properties of Aceclofenac by using chitosan and water soluble chitosan. Int J Pharm Pharm Sci 5(1):414–419Google Scholar
  37. George M, Abraham TE (2006a) Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan—a review. J Control Release 114(1):1–14PubMedCrossRefPubMedCentralGoogle Scholar
  38. George M, Abraham TE (2006b) Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan--a review. J Control Release 114(1):1–14PubMedCrossRefPubMedCentralGoogle Scholar
  39. Ghaffari A et al (2007) Preparation and characterization of free mixed-film of pectin/chitosan/Eudragit® RS intended for sigmoidal drug delivery. Eur J Pharm Biopharm 67(1):175–186PubMedCrossRefGoogle Scholar
  40. Gupta K, Kumar MR (2000) Drug release behavior of beads and microgranules of chitosan. Biomaterials 21(11):1115–1119PubMedCrossRefGoogle Scholar
  41. Hadisoewignyo L et al (2018) Evaluation of anti-inflammatory activity and biocompatibility of curcumin loaded mesoporous silica nanoparticles as an oral drug delivery system. Adv Nat Sci Nanosci Nanotechnol 9(3):035007CrossRefGoogle Scholar
  42. Hari P, Chandy T, Sharma CP (1996a) Chitosan/calcium–alginate beads for oral delivery of insulin. J Appl Polym Sci 59(11):1795–1801CrossRefGoogle Scholar
  43. Hari P, Chandy T, Sharma CP (1996b) Chitosan/calcium alginate microcapsules for intestinal delivery of nitrofurantoin. J Microencapsul 13(3):319–329PubMedCrossRefGoogle Scholar
  44. He C et al (2015) Optimization of multifunctional chitosan–siRNA nanoparticles for oral delivery applications, targeting TNF-α silencing in rats. Acta Biomater 17:98–106PubMedCrossRefGoogle Scholar
  45. Hejazi R, Amiji M (2003) Chitosan-based gastrointestinal delivery systems. J Control Release 89(2):151–165PubMedCrossRefGoogle Scholar
  46. Helmy AM et al (2017) Development and in vivo evaluation of chitosan beads for the colonic delivery of azathioprine for treatment of inflammatory bowel disease. Eur J Pharm Sci 109:269–279PubMedCrossRefGoogle Scholar
  47. HOU W et al (1985) Sustained release of indomethacin from chitosan granules. Chem Pharm Bull 33(9):3986–3992PubMedCrossRefGoogle Scholar
  48. Huang J et al (2015) Layer-by-layer assembled milk protein coated magnetic nanoparticle enabled oral drug delivery with high stability in stomach and enzyme-responsive release in small intestine. Biomaterials 39:105–113PubMedCrossRefGoogle Scholar
  49. Huang T et al (2018) Chitosan-DNA nanoparticles enhanced the immunogenicity of multivalent DNA vaccination on mice against Trueperella pyogenes infection. J Nanobiotechnol 16(1):8CrossRefGoogle Scholar
  50. Jin R et al (2007) Enzyme-mediated fast in situ formation of hydrogels from dextran–tyramine conjugates. Biomaterials 28(18):2791–2800PubMedCrossRefGoogle Scholar
  51. Kafedjiiski K et al (2005a) Synthesis and in vitro evaluation of a novel chitosan–glutathione conjugate. Pharm Res 22(9):1480–1488PubMedCrossRefGoogle Scholar
  52. Kafedjiiski K et al (2005b) Synthesis and in vitro evaluation of a novel thiolated chitosan. Biomaterials 26(7):819–826PubMedCrossRefGoogle Scholar
  53. Kast CE, Bernkop-Schnürch A (2001) Thiolated polymers—thiomers: development and in vitro evaluation of chitosan–thioglycolic acid conjugates. Biomaterials 22(17):2345–2352PubMedCrossRefGoogle Scholar
  54. Kawashima Y et al (1985) Preparation of a prolonged release tablet of aspirin with chitosan. Chem Pharm Bull 33(5):2107–2113PubMedCrossRefGoogle Scholar
  55. Khan TA, Peh KK, Ch’ng HS (2002) Reporting degree of deacetylation values of chitosan: the influence of analytical methods. J Pharm Pharmaceut Sci 5(3):205–212Google Scholar
  56. Khan F, Tares RS, Oreffo ROC, Bradley M (2009) Versatile biocompatible polymer hydrogels: scaffolds for cell growth. Angew Chem Int Ed 48:978–982CrossRefGoogle Scholar
  57. Kim MS et al (2007) Synthesis and characterization of in situ chitosan-based hydrogel via grafting of carboxyethyl acrylate. J Biomed Mater Res A 83(3):674–682CrossRefGoogle Scholar
  58. Kohane DS, Langer R (2008) Polymeric biomaterials in tissue engineering. Pediatr Res 3:487–491CrossRefGoogle Scholar
  59. Kulkarni N, Wakte P, Naik J (2015) Development of floating chitosan-xanthan beads for oral controlled release of glipizide. Int J Pharm Investig 5(2):73PubMedPubMedCentralCrossRefGoogle Scholar
  60. Kumar MR et al (2004) Chitosan chemistry and pharmaceutical perspectives. Chem Rev 104(12):6017–6084PubMedCrossRefGoogle Scholar
  61. Kumar B, Mahaboobi S, Satyam S (2017) Chitosan in medicine–a mini review. J Mol Pharm Org Process Res 5(134):2Google Scholar
  62. Lau JL, Dunn MK (2018) Therapeutic peptides: historical perspectives, current development trends, and future directions. Bioorg Med Chem 26(10):2700–2707PubMedCrossRefGoogle Scholar
  63. Lin C-C, Lin C-W (2009) Preparation of N, O-carboxymethyl chitosan nanoparticles as an insulin carrier. Drug Deliv 16(8):458–464PubMedCrossRefGoogle Scholar
  64. Lin CC, Metters AT (2006) Hydrogels in controlled release formulations: network design and mathematical modeling. Adv Drug Deliv Rev 58:1379–1408PubMedCrossRefGoogle Scholar
  65. Lin YH et al (2005) Physically crosslinked alginate/N,O-carboxymethyl chitosan hydrogels with calcium for oral delivery of protein drugs. Biomaterials 26(14):2105–2113PubMedCrossRefGoogle Scholar
  66. Liu Y et al (2016) Nano-polyplex based on oleoyl-carboxymethy-chitosan (OCMCS) and hyaluronic acid for oral gene vaccine delivery. Colloids Surf B: Biointerfaces 145:492–501PubMedCrossRefGoogle Scholar
  67. Mandracchia D et al (2017) In vitro evaluation of glycol chitosan based formulations as oral delivery systems for efflux pump inhibition. Carbohydr Polym 166:73–82PubMedCrossRefGoogle Scholar
  68. Mansourpour M et al (2015) Development of acid-resistant alginate/trimethyl chitosan nanoparticles containing cationic β-cyclodextrin polymers for insulin oral delivery. AAPS PharmSciTech 16(4):952–962PubMedPubMedCentralCrossRefGoogle Scholar
  69. Martien R et al (2007) Chitosan-thioglycolic acid conjugate: an alternative carrier for oral nonviral gene delivery? J Biomed Mater Res A 82(1):1–9PubMedCrossRefGoogle Scholar
  70. Mi FL et al (1997) Chitosan tablets for controlled release of theophylline: effect of polymer—drug wet or dry blending and anionic—cationic interpolymer complex. J Appl Polym Sci 66(13):2495–2505CrossRefGoogle Scholar
  71. Millotti G et al (2014) In vivo evaluation of thiolated chitosan tablets for oral insulin delivery. J Pharm Sci 103(10):3165–3170PubMedCrossRefGoogle Scholar
  72. MIYAZAKI S et al (1988a) Sustained-release and intragastric-floating granules of indomethacin using chitosan in rabbits. Chem Pharm Bull 36(10):4033–4038PubMedCrossRefGoogle Scholar
  73. MIYAZAKI S et al (1988b) Sustained release of indomethacin from chitosan granules in beagle dogs. J Pharm Pharmacol 40(9):642–643PubMedCrossRefGoogle Scholar
  74. Mokhtare B et al (2017) In vitro and in vivo evaluation of alginate and alginatechitosan beads containing metformin hydrochloride. Trop J Pharm Res 16(2):287–296CrossRefGoogle Scholar
  75. Montero-Padilla S, Velaga S, Morales JO (2017) Buccal dosage forms: general considerations for pediatric patients. AAPS PharmSciTech 18(2):273–282PubMedCrossRefGoogle Scholar
  76. Mukhopadhyay P et al (2013) Formulation of pH-responsive carboxymethyl chitosan and alginate beads for the oral delivery of insulin. J Appl Polym Sci 129(2):835–845CrossRefGoogle Scholar
  77. Mutalik S et al (2008) Enhancement of dissolution rate and bioavailability of aceclofenac: a chitosan-based solvent change approach. Int J Pharm 350(1–2):279–290PubMedCrossRefGoogle Scholar
  78. Narayanan D et al (2013) In vitro and in vivo evaluation of osteoporosis therapeutic peptide PTH 1–34 loaded PEGylated chitosan nanoparticles. Mol Pharm 10(11):4159–4167PubMedCrossRefGoogle Scholar
  79. Ono K et al (2000) Photocrosslinkable chitosan as a biological adhesive. J Biomed Mater Res 49(2):289–295PubMedCrossRefGoogle Scholar
  80. Park S-H, Chun M-K, Choi H-K (2008) Preparation of an extended-release matrix tablet using chitosan/Carbopol interpolymer complex. Int J Pharm 347(1–2):39–44PubMedCrossRefGoogle Scholar
  81. Park H, Park K, Shalaby WS (2011) Biodegradable hydrogels for drug delivery. CRC Press, LancasterGoogle Scholar
  82. Pasparakis G, Bouropoulos N (2006) Swelling studies and in vitro release of verapamil from calcium alginate and calcium alginate–chitosan beads. Int J Pharm 323(1–2):34–42PubMedCrossRefGoogle Scholar
  83. Patel A (2016) Mucoadhesive Buccal films based on chitosan and Carboxymethylated Feronia Limonia fruit pulp mucilage Interpolymer complex for delivery of opioid analgesics. Asian J Pharm 10(2):137Google Scholar
  84. Peppas NA, Bures P, Leobandung W, Ichikawa H (2000) Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 50:27–46PubMedCrossRefGoogle Scholar
  85. Perugini P et al (2003) Periodontal delivery of ipriflavone: new chitosan/PLGA film delivery system for a lipophilic drug. Int J Pharm 252(1–2):1–9PubMedCrossRefGoogle Scholar
  86. Quade-Lyssy P et al (2014) Oral gene therapy for hemophilia B using chitosan-formulated FIX mutants. J Thromb Haemost 12(6):932–942PubMedCrossRefGoogle Scholar
  87. Rao NR et al (2010) Preparation and characterization of ionotropic cross-linked chitosan microparticles for controlled release of aceclofenac. Int J Pharm Sci Drug Res 2(2):107–111Google Scholar
  88. Remunan-Lopez C et al (1998) Design and evaluation of chitosan/ethylcellulose mucoadhesive bilayered devices for buccal drug delivery. J Control Release 55(2–3):143–152PubMedCrossRefGoogle Scholar
  89. Renu S et al (2018) Engineering of targeted Mucoadhesive chitosan based Salmonella Nanovaccine for oral delivery in poultry. Am Assoc Immnol 200:118.15Google Scholar
  90. Richard J (2017) Challenges in oral peptide delivery: lessons learnt from the clinic and future prospects. Ther Deliv 8(8):663–684PubMedCrossRefGoogle Scholar
  91. Roy K et al (1999) Oral gene delivery with chitosan–DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat Med 5(4):387PubMedCrossRefGoogle Scholar
  92. Roy I, Sardar M, Gupta MN (2003) Hydrolysis of chitin by Pectinex™. Enzym Microb Technol 32(5):582–588CrossRefGoogle Scholar
  93. Sabnis S, Rege P, Block LH (1997) Use of chitosan in compressed tablets of diclofenac sodium: inhibition of drug release in an acidic environment. Pharm Dev Technol 2(3):243–255PubMedCrossRefGoogle Scholar
  94. Sadeghi A et al (2008a) Permeation enhancer effect of chitosan and chitosan derivatives: comparison of formulations as soluble polymers and nanoparticulate systems on insulin absorption in Caco-2 cells. Eur J Pharm Biopharm 70(1):270–278PubMedCrossRefGoogle Scholar
  95. Sadeghi A et al (2008b) Preparation, characterization and antibacterial activities of chitosan, N-trimethyl chitosan (TMC) and N-diethylmethyl chitosan (DEMC) nanoparticles loaded with insulin using both the ionotropic gelation and polyelectrolyte complexation methods. Int J Pharm 355(1–2):299–306PubMedCrossRefGoogle Scholar
  96. Şenel S et al (2000) Chitosan films and hydrogels of chlorhexidine gluconate for oral mucosal delivery. Int J Pharm 193(2):197–203PubMedCrossRefGoogle Scholar
  97. Shalaby TI, El-Refaie WM (2018) Bioadhesive chitosan-coated cationic nanoliposomes with improved insulin encapsulation and prolonged oral hypoglycemic effect in diabetic mice. J Pharm Sci 107:2136PubMedCrossRefGoogle Scholar
  98. Shimono N et al (2002) Chitosan dispersed system for colon-specific drug delivery. Int J Pharm 245(1–2):45–54PubMedCrossRefGoogle Scholar
  99. Shu X, Zhu K (2002) Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure. Int J Pharm 233(1–2):217–225PubMedCrossRefGoogle Scholar
  100. Sinha V, Kumria R (2002) Binders for colon specific drug delivery: an in vitro evaluation. Int J Pharm 249(1–2):23–31PubMedCrossRefGoogle Scholar
  101. Sithole MN et al (2017) A review of semi-synthetic biopolymer complexes: modified polysaccharide nano-carriers for enhancement of oral drug bioavailability. Pharm Dev Technol 22(2):283–295PubMedCrossRefGoogle Scholar
  102. Soares E, Jesus S, Borges O (2018) Oral hepatitis B vaccine: chitosan or glucan based delivery systems for efficient HBsAg immunization following subcutaneous priming. Int J Pharm 535(1–2):261–271PubMedCrossRefGoogle Scholar
  103. Sogias IA, Williams AC, Khutoryanskiy VV (2012) Chitosan-based mucoadhesive tablets for oral delivery of ibuprofen. Int J Pharm 436(1–2):602–610PubMedCrossRefGoogle Scholar
  104. Spinks CB et al (2017) Pharmaceutical characterization of novel tenofovir liposomal formulations for enhanced oral drug delivery: in vitro pharmaceutics and Caco-2 permeability investigations. Clin Pharmacol Adv Appl 9:29Google Scholar
  105. Sutton SC, Nause R, Gandelman K (2017) The impact of gastric pH, volume, and emptying on the food effect of ziprasidone oral absorption. AAPS J 19(4):1084–1090PubMedCrossRefGoogle Scholar
  106. Takka S, Gürel A (2010) Evaluation of chitosan/alginate beads using experimental design: formulation and in vitro characterization. AAPS PharmSciTech 11(1):460–466PubMedPubMedCentralCrossRefGoogle Scholar
  107. Tan H, Wu YC, Payne KA, Marra KG (2004) A novel pH-sensitivehydrogel composed of N, O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery. J Control Release 96:285–300CrossRefGoogle Scholar
  108. Tan H et al (2009) Injectable in situ forming biodegradable chitosan–hyaluronic acid based hydrogels for cartilage tissue engineering. Biomaterials 30(13):2499–2506PubMedPubMedCentralCrossRefGoogle Scholar
  109. Tang C et al (2014) Preparation of ibuprofen-loaded chitosan films for oral mucosal drug delivery using supercritical solution impregnation. Int J Pharm 473(1–2):434–441PubMedCrossRefGoogle Scholar
  110. Tapia C et al (2004) Comparative studies on polyelectrolyte complexes and mixtures of chitosan–alginate and chitosan–carrageenan as prolonged diltiazem clorhydrate release systems. Eur J Pharm Biopharm 57(1):65–75PubMedCrossRefGoogle Scholar
  111. Teruel AH et al (2018) Smart gated magnetic silica mesoporous particles for targeted colon drug delivery: new approaches for inflammatory bowel diseases treatment. J Control Release 281:58–69PubMedCrossRefGoogle Scholar
  112. Thanou M et al (2000) Effect of degree of quaternization of N-trimethyl chitosan chloride for enhanced transport of hydrophilic compounds across intestinal Caco-2 cell monolayers. J Control Release 64(1–3):15–25PubMedCrossRefGoogle Scholar
  113. Tobio M et al (1998) Stealth PLA-PEG nanoparticles as protein carriers for nasal administration. Pharm Res 15(2):270–275PubMedCrossRefGoogle Scholar
  114. Tobıo M et al (2000) The role of PEG on the stability in digestive fluids and in vivo fate of PEG-PLA nanoparticles following oral administration. Colloids Surf B: Biointerfaces 18(3–4):315–323PubMedCrossRefGoogle Scholar
  115. Tozaki H et al (1997) Chitosan capsules for colon-specific drug delivery: improvement of insulin absorption from the rat colon. J Pharm Sci 86(9):1016–1021PubMedCrossRefGoogle Scholar
  116. TOZAKI H et al (1999) Validation of a pharmacokinetic model of Colon-specific drug delivery and the therapeutic effects of chitosan capsules containing 5-Aminosalicylic acid on 2, 4, 6-Trinitrobenzenesulphonic acid-induced colitis in rats. J Pharm Pharmacol 51(10):1107–1112PubMedCrossRefGoogle Scholar
  117. Tozaki H et al (2002) Chitosan capsules for colon-specific drug delivery: enhanced localization of 5-aminosalicylic acid in the large intestine accelerates healing of TNBS-induced colitis in rats. J Control Release 82(1):51–61PubMedCrossRefGoogle Scholar
  118. Valero Y et al (2016) An oral chitosan DNA vaccine against nodavirus improves transcription of cell-mediated cytotoxicity and interferon genes in the European sea bass juveniles gut and survival upon infection. Dev Comp Immunol 65:64–72PubMedCrossRefGoogle Scholar
  119. Varshosaz J et al (2015) Polyelectrolyte complexes of chitosan for production of sustained release tablets of bupropion HCL. Farmacia 63(1):65–73Google Scholar
  120. Wang K, He Z (2002) Alginate–konjac glucomannan–chitosan beads as controlled release matrix. Int J Pharm 244(1–2):117–126PubMedCrossRefGoogle Scholar
  121. Wang E et al (2018) Preparation, characterization and evaluation of the immune effect of alginate/chitosan composite microspheres encapsulating recombinant protein of Streptococcus iniae designed for fish oral vaccination. Fish Shellfish Immunol 73:262–271PubMedCrossRefGoogle Scholar
  122. Wedmore I et al (2006) A special report on the chitosan-based hemostatic dressing: experience in current combat operations. J Trauma Acute Care Surg 60(3):655–658CrossRefGoogle Scholar
  123. Werle M, Bernkop-Schnürch A (2008) Thiolated chitosans: useful excipients for oral drug delivery. J Pharm Pharmacol 60(3):273–281PubMedCrossRefGoogle Scholar
  124. Werle M, Hoffer M (2006) Glutathione and thiolated chitosan inhibit multidrug resistance P-glycoprotein activity in excised small intestine. J Control Release 111(1–2):41–46PubMedCrossRefGoogle Scholar
  125. Werle M, Takeuchi H, Bernkop-Schnürch A (2009) Modified chitosans for oral drug delivery. J Pharm Sci 98(5):1643–1656PubMedCrossRefGoogle Scholar
  126. Wichterle O, Lim D (1960) Hydrophilic gels for biological use. Nature 185:117–118CrossRefGoogle Scholar
  127. Xu Y et al (2007) Preparation of dual crosslinked alginate–chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system. Int J Pharm 336(2):329–337PubMedCrossRefGoogle Scholar
  128. Yao KD et al (1994) Swelling kinetics and release characteristic of crosslinked chitosan: polyether polymer network (semi-IPN) hydrogels. J Polym Sci A Polym Chem 32(7):1213–1223CrossRefGoogle Scholar
  129. Zeng N et al (2017) Cyanine derivative as a suitable marker for thermosensitive in situ gelling delivery systems: in vitro and in vivo validation of a sustained buccal drug delivery. Int J Pharm 534(1–2):128–135PubMedCrossRefGoogle Scholar
  130. Zhang M et al (2002a) Properties and biocompatibility of chitosan films modified by blending with PEG. Biomaterials 23(13):2641–2648PubMedCrossRefGoogle Scholar
  131. Zhang H, Alsarra IA, Neau SH (2002b) An in vitro evaluation of a chitosan-containing multiparticulate system for macromolecule delivery to the colon. Int J Pharm 239(1–2):197–205PubMedCrossRefGoogle Scholar
  132. Zhao K et al (2014) Chitosan-coated poly (lactic-co-glycolic) acid nanoparticles as an efficient delivery system for Newcastle disease virus DNA vaccine. Int J Nanomedicine 9:4609PubMedPubMedCentralCrossRefGoogle Scholar
  133. Zheng H, Tang C, Yin C (2015) Oral delivery of shRNA based on amino acid modified chitosan for improved antitumor efficacy. Biomaterials 70:126–137PubMedCrossRefGoogle Scholar
  134. Zheng F et al (2016) Development of oral DNA vaccine based on chitosan nanoparticles for the immunization against reddish body iridovirus in turbots (Scophthalmus maximus). Aquaculture 452:263–271CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Reza Baradaran Eftekhari
    • 1
  • Niloufar Maghsoudnia
    • 1
  • Shabnam Samimi
    • 1
  • Farid Abedin Dorkoosh
    • 1
    • 2
    Email author
  1. 1.Department of Pharmaceutics, Faculty of PharmacyTehran University of Medical SciencesTehranIran
  2. 2.Medical Biomaterial Research Center (MBRC)Tehran University of Medical SciencesTehranIran

Personalised recommendations