Polymer-based Oral Peptide Nanomedicines

• Walsh G . Biopharmaceutical benchmarks 2006. Nat. Biotechnol.24(7), 769–776 (2006).
   PubMed Web of Science ®Google Scholar
• Johnson-Leger C , PowerCA, ShomadeG, ShawJP, El Proudfoot EI. Protein therapeutics – lessons learned and a view of the future. Exp. Opin. Biol. Ther.6(1), 1–7 (2006).
   PubMed Web of Science ®Google Scholar
• Degim IT , CelebiN. Controlled delivery of peptides and proteins. Curr. Pharm. Des.13(1), 99–117 (2007).
   PubMed Web of Science ®Google Scholar
• Reichert J . Development trends for peptide therapeutics: a comprehensive quantitative analysis of peptide therapeutics in clinical development. In: Peptide Therapeutics Foundation. Peptide Therapeutics Foundation, Macmillan Publishers, London, UK (2010).
   Google Scholar
• Adessi C , SotoC. Converting a peptide into a drug: strategies to improve stability and bioavailability. Curr. Med. Chem.9(9), 963–978 (2002).
   PubMed Web of Science ®Google Scholar
• Shaji J , PatoleV. Protein and peptide drug delivery: oral approaches. Ind. J. Pharm. Sci.70(3), 269–277 (2008).
   PubMed Web of Science ®Google Scholar
• Hoffman A , ZivE. Pharmacokinetic considerations of new insulin formulations and routes of administration. Clin. Pharm.33(4), 285–301 (1997).
   Google Scholar
• Bernkop-Schnurch A , WalkerG. Multifunctional matrices for oral peptide delivery. Crit. Rev. Ther. Drug Carr. Syst.18(5), 459–501 (2001).
   PubMed Web of Science ®Google Scholar
• Gabor F , BognerE, WeissenboeckA, WirthM. The lectin-cell interaction and its implications to intestinal lectin-mediated drug delivery. Adv. Drug Deliv. Rev.56(4), 459–480 (2004).
   PubMed Web of Science ®Google Scholar
• Lee VHL , TraverRD, TaubME. Enzymatic barriers to peptide and protein drug delivery. In: Peptide and Protein Drug Delivery. Lee VHL (Ed.). Marcel Dekker Inc., NY, USA (1991).
   Google Scholar
• Woodley JF . Enzymatic barriers for GI peptide and protein delivery. Crit. Rev. Ther. Drug Carr. Syst.11(2–3), 61–95 (1994).
   PubMed Web of Science ®Google Scholar
• Salama NN , EddingtonND, FasanoA. Tight junction modulation and its relationship to drug delivery. Adv. Drug Deliv. Rev.58(1), 15–28 (2006).
   PubMed Web of Science ®Google Scholar
• Ward PD , TippinTK, ThakkerDR. Enhancing paracellular permeability by modulating epithelial tight junctions. Pharm. Sci. Technol. Today3(10), 346–358 (2000).
   PubMedGoogle Scholar
• Borges O , Cordeiro-da-SilvaA, RomeijnSGet al. Uptake studies in rat Peyer‘s patches, cytotoxicity and release studies of alginate coated chitosan nanoparticles for mucosal vaccination. J. Control. Release 114(3), 348–358 (2006).
   PubMed Web of Science ®Google Scholar
• Wu ZH , PingQN, WeiY, LaiJM. Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice. Acta Pharm. Sin.25(7), 966–972 (2004).
   PubMed Web of Science ®Google Scholar
• Adams G , WangN, CuiY. Future alternative therapies in a quest to halt aberrations in diabetes mellitus. Biomed. Pharm.59(6), 296–301 (2005).
   PubMed Web of Science ®Google Scholar
• Rubio-Aliaga I , DanielH. Mammalian peptide transporters as targets for drug delivery. Trends Pharm. Sci.23(9), 434–440 (2002).
   PubMed Web of Science ®Google Scholar
• Maher S , FeigheryL, BraydenD, McCleanSN. Melittin as a permeability enhancer II: in vitro investigations in human mucus secreting intestinal monolayers and rat colonic mucosae. Pharm. Res.24(7), 1346–1356 (2007).
   PubMed Web of Science ®Google Scholar
• Maher S , DevocelleM, RyanSA, McCleanSN, BraydenDJ. Impact of amino acid replacements on in vitro permeation enhancement and cytotoxicity of the intestinal absorption promoter, melittin. Int. J. Pharm.387(1–2), 154–160 (2010).
   PubMedGoogle Scholar
• Kamei N , MorishitaM, KanayamaYet al. Molecular imaging analysis of intestinal insulin absorption boosted by cell-penetrating peptides by using positron emission tomography. J. Control. Release 146(1), 16–22 (2010).
   PubMed Web of Science ®Google Scholar
• Kamei N , MorishitaM, TakayamaK. Importance of intermolecular interaction on the improvement of intestinal therapeutic peptide/protein absorption using cell-penetrating peptides. J. Control. Release136(3), 179–186 (2009).
   PubMed Web of Science ®Google Scholar
• Duncan R . Polymer conjugates as anticancer nanomedicines. Nat. Rev. Cancer6(9), 688–701 (2006).
   PubMed Web of Science ®Google Scholar
• Kahns AH , BuurA, BundgaardH. Prodrugs of peptides. Synthesis and evaluation of various esters of desmopressin (dDAVP). Pharm. Res.10(1), 68–74 (1993).
   PubMed Web of Science ®Google Scholar
• Uchiyama T , KotaniA, TatsumiHet al. Development of novel lipophilic derivatives of DADLE (leucine enkephalin analogue): intestinal permeability characteristics of DADLE derivatives in rats. Pharm. Res. 17(12), 1461–1467 (2000).
   PubMed Web of Science ®Google Scholar
• Asada H , DouenT, MizokoshiYet al. Stability of acyl derivatives of insulin in the small intestine: relative importance of insulin association characteristics in aqueous solution. Pharm. Res. 11(8), 1115–1120 (1994).
   PubMed Web of Science ®Google Scholar
• Swaan PW . Recent advances in intestinal macromolecular drug delivery via receptor-mediated transport pathways. Pharm. Res.15(6), 826–834 (1998).
   PubMed Web of Science ®Google Scholar
• Oh DM , HanHK, AmidonGL. Drug transport and targeting. Intestinal transport. Pharm. Biotechnol.12, 59–88 (1999).
   PubMedGoogle Scholar
• Pauletti GM , GangwarS, KnippGTet al. Structural requirements for intestinal absorption of peptide drugs. J. Control. Release 41(1–2), 3–17 (1996).
   Web of Science ®Google Scholar
• Desai MP , LabhasetwarV, WalterE, LevyRJ, AmidonGL. The mechanism of uptake of biodegradable microparticles in Caco-2 cells is size dependent. Pharm. Res.14(11), 1568–1573 (1997).
   PubMed Web of Science ®Google Scholar
• Koziara JM , LockmanPR, AllenDD, MumperRJ. In situ blood–brain barrier transport of nanoparticles. Pharm. Res.20(11), 1772–1778 (2003).
   PubMed Web of Science ®Google Scholar
• Vila A , SanchezA, TobioM, CalvoP, AlonsoMJ. Design of biodegradable particles for protein delivery. J. Control. Release78(1–3), 15–24 (2002).
   PubMed Web of Science ®Google Scholar
• Tobío M , SánchezA, VilaAet al. The role of PEG on the stability in digestive fluids and in vivo fate of PEG–PLA nanoparticles following oral administration. Coll. Surf. B Biointerfaces 18(3–4), 315–323 (2000).
   PubMed Web of Science ®Google Scholar
• Gao H , WangYN, FanYG, MaJB. Synthesis of a biodegradable tadpole-shaped polymer via the coupling reaction of polylactide onto mono(6-(2-aminoethyl)amino-6-deoxy)-cyclodextrin and its properties as the new carrier of protein delivery system. J. Control. Release107(1), 158–173 (2005).
   PubMed Web of Science ®Google Scholar
• Carino GP , JacobJS, MathiowitzE. Nanosphere based oral insulin delivery. J. Control. Release65(1–2), 261–269 (2000).
   PubMed Web of Science ®Google Scholar
• Cui FD , TaoAJ, CunDM, ZhangLQ, ShiK. Preparation of insulin loaded PLGA–Hp55 nanoparticles for oral delivery. J. Pharm. Sci.96(2), 421–427 (2007).
   PubMed Web of Science ®Google Scholar
• Gutierro I , HernandezRM, IgartuaM, GasconAR, PedrazJL. Size dependent immune response after subcutaneous, oral and intranasal administration of BSA loaded nanospheres. Vaccine21(1–2), 67–77 (2002).
   PubMed Web of Science ®Google Scholar
• Satheesh Kumar P , RamakrishnaS, Ram Saini T, Diwan PV. Influence of microencapsulation method and peptide loading on formulation of poly(lactide-co-glycolide) insulin nanoparticles. Die Pharmazie Int. J. Pharm. Sci.61(7), 613–617 (2006).
   Google Scholar
• Yoo HS , ParkTG. Biodegradable nanoparticles containing protein–fatty acid complexes for oral delivery of salmon calcitonin. J. Pharm. Sci.93(2), 488–495 (2004).
   PubMed Web of Science ®Google Scholar
• Kawashima Y , YamamotoH, TakeuchiH, KunoY. Mucoadhesive DL-lactide/glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin. Pharm. Dev. Technol.5(1), 77–85 (2000).
   PubMed Web of Science ®Google Scholar
• Damgé C , SochaM, UbrichN, MaincentP. Poly(ε-caprolactone)/eudragit nanoparticles for oral delivery of aspart-insulin in the treatment of diabetes. J. Pharm. Sci.99(2), 879–889 (2010).
   PubMed Web of Science ®Google Scholar
• Damgé C , MaincentP, UbrichN. Oral delivery of insulin associated to polymeric nanoparticles in diabetic rats. J. Control. Release117(2), 163–170 (2007).
   PubMed Web of Science ®Google Scholar
• Cui F , QianF, ZhaoZ, YinL, TangC, YinC. Preparation, characterization, and oral delivery of insulin loaded carboxylated chitosan grafted poly(methyl methacrylate) nanoparticles. Biomacromolecules10(5), 1253–1258 (2009).
   PubMed Web of Science ®Google Scholar
• Sajeesh S , SharmaCP. Cyclodextrin-insulin complex encapsulated polymethacrylic acid based nanoparticles for oral insulin delivery. Int. J. Pharm.325(1–2), 147–154 (2006).
   PubMed Web of Science ®Google Scholar
• Torres-Lugo M , PeppasNA. Preparation and characterization of P(MAA-g-EG) nanospheres for protein delivery applications. J. Nanopart. Res.4(1), 73–81 (2002).
   Web of Science ®Google Scholar
• Vauthier C , DubernetC, FattalE, Pinto-AlphandaryH, CouvreurP. Poly(alkylcyanoacrylates) as biodegradable materials for biomedical applications. Adv. Drug Deliv. Rev.55(4), 519–548 (2003).
   PubMed Web of Science ®Google Scholar
• Damgé C , CouvreurP. A new approach for oral administration of insulin using polyalkylcyanoacrylate nanocapsules as a drug carrier. Diabetes37(2), 246–251 (1988).
   PubMed Web of Science ®Google Scholar
• Lowe PJ , TempleCS. Calcitonin and Insulin in Isobutylcyanoacrylate Nanocapsules: Protection Against Proteases and Effect on Intestinal Absorption in Rats. Blackwell Publishing Ltd, London, UK, 547–552 (1994).
   Google Scholar
• Damgé C , VonderscherJ, MarbachP, PingetM. Poly(alkyl cyanoacrylate) nanocapsules as a delivery system in the rat for octreotide, a long-acting somatostatin analogue. J. Pharm. Pharmacol.49(10), 949–954 (1997).
   PubMed Web of Science ®Google Scholar
• Graf A , RadesT, HookSM. Oral insulin delivery using nanoparticles based on microemulsions with different structure-types: optimisation and in vivo evaluation. Eur. J. Pharm. Sci.37(1), 53–61 (2009).
   PubMed Web of Science ®Google Scholar
• Mesiha MS , SidhomMB, FasipeB. Oral and subcutaneous absorption of insulin poly(isobutylcyanoacrylate) nanoparticles. Int. J. Pharm.288(2), 289–293 (2005).
   PubMedGoogle Scholar
• des Rieux A , FievezV, GarinotM, Schneider Y-J, Preat VR. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J. Control. Release116(1), 1–27 (2006).
   PubMed Web of Science ®Google Scholar
• Krause HJ , SchwarzA, RohdewaldP. Polylactic acid nanoparticles, a colloidal drug delivery system for lipophilic drugs. Int. J. Pharm.27(2–3), 145–155 (1985).
   Web of Science ®Google Scholar
• Fonseca C , SimoesSR, GasparRR. Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J. Control. Release83(2), 273–286 (2002).
   PubMed Web of Science ®Google Scholar
• Lemoine D , PreatV. Polymeric nanoparticles as delivery system for influenza virus glycoproteins. J. Control. Release54(1), 15–27 (1998).
   PubMed Web of Science ®Google Scholar
• Leo E , BrinaB, ForniF, VandelliMA. In vitro evaluation of PLA nanoparticles containing a lipophilic drug in water-soluble or insoluble form. Int. J. Pharm.278(1), 133–141 (2004).
   PubMedGoogle Scholar
• Dillen K , VandervoortJ, Van den Mooter G, Verheyden L, Ludwig A. Factorial design, physicochemical characterisation and activity of ciprofloxacin–PLGA nanoparticles. Int. J. Pharm.275(1–2), 171–187 (2004).
   PubMed Web of Science ®Google Scholar
• Langer RS , PeppasNA. Present and future applications of biomaterials in controlled drug delivery systems. Biomaterials2(4), 201–214 (1981).
   PubMed Web of Science ®Google Scholar
• Zambaux MF , BonneauxF, GrefR, DellacherieE, VigneronC. Preparation and characterization of protein C-loaded PLA nanoparticles. J. Control. Release60(2–3), 179–188 (1999).
   PubMed Web of Science ®Google Scholar
• Galindo-Rodriguez SA , AllemannE, FessiH, DoelkerE. Polymeric nanoparticles for oral delivery of drugs and vaccines: a critical evaluation of in vivo studies. 22(5), 419–464 (2005).
   Google Scholar
• Alonso-Sande MA , CunaM, Remunan-LopezC, Teijeiro-OsorioDE, Alonso-LebreroJL, AlonsoMAJ. Formation of new glucomannan-chitosan nanoparticles and study of their ability to associate and deliver proteins. Macromolecules39(12), 4152–4158 (2006).
   Web of Science ®Google Scholar
• Calvo P , Remunan-LopezC, Vila-JatoJL, AlonsoMAJ. Chitosan and chitosan/ethylene oxide-propylene oxide block copolymer nanoparticles as novel carriers for proteins and vaccines. Pharm. Res.14(10), 1431–1436 (1997).
   PubMed Web of Science ®Google Scholar
• Calvo P , Remuñán-LópezC, Vila-JatoJL, AlonsoMJ. Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers. J. Appl. Polym. Sci.63(1), 125–132 (1997).
   Web of Science ®Google Scholar
• Balthasar S , MichaelisK, DinauerN, von Briesen H, Kreuter JR, Langer K. Preparation and characterisation of antibody modified gelatin nanoparticles as drug carrier system for uptake in lymphocytes. Biomaterials26(15), 2723–2732 (2005).
   PubMed Web of Science ®Google Scholar
• Reis CP , RibeiroAJ, HoungS, VeigaF, NeufeldRJ. Nanoparticulate delivery system for insulin: design, characterization and in vitro/in vivo bioactivity. Eur. J. Pharm. Sci.30(5), 392–397 (2007).
   PubMed Web of Science ®Google Scholar
• Reis CP , VeigaFJ, RibeiroAJ, NeufeldRJ, DamgéC. Nanoparticulate biopolymers deliver insulin orally eliciting pharmacological response. J. Pharm. Sci.97(12), 5290–5305 (2008).
   PubMed Web of Science ®Google Scholar
• Chalasani KB , Russell-JonesGJ, JainAK, DiwanPV, JainSK. Effective oral delivery of insulin in animal models using vitamin B12-coated dextran nanoparticles. J. Control. Release122(2), 141–150 (2007).
   PubMed Web of Science ®Google Scholar
• Parajó Y , D´AngeloI, WelleA, Garcia-FuentesM, AlonsoMJ. Hyaluronic acid/chitosan nanoparticles as delivery vehicles for VEGF and PDGF-BB. Drug Deliv.17(8), 596–604 (2010).
   PubMed Web of Science ®Google Scholar
• Trapani A , LopedotaA, FrancoMet al. A comparative study of chitosan and chitosan/cyclodextrin nanoparticles as potential carriers for the oral delivery of small peptides. Eur. J. Pharm. Biopharm. 75(1), 26–32 (2010).
   PubMed Web of Science ®Google Scholar
• Bernkop-Schnurch A , KraulandAH, LeitnerVM, PalmbergerT. Thiomers: potential excipients for non-invasive peptide delivery systems. Eur. J. Pharm. Biopharm.58(2), 253–263 (2004).
   PubMed Web of Science ®Google Scholar
• Deutel B , GreindlM, ThaurerM, Bernkop-SchnuerchA. Novel insulin thiomer nanoparticles: in vivo evaluation of an oral drug delivery system. Biomacromolecules9(1), 278–285 (2008).
   PubMed Web of Science ®Google Scholar
• Roldo M , HornofM, CalicetiP, Bernkop-SchnurchA. Mucoadhesive thiolated chitosans as platforms for oral controlled drug delivery: synthesis and in vitro evaluation. Eur. J. Pharm. Biopharm.57(1), 115–121 (2004).
   PubMed Web of Science ®Google Scholar
• Woitiski CB , NeufeldRJ, RibeiroANJ, VeigaF. Colloidal carrier integrating biomaterials for oral insulin delivery: influence of component formulation on physicochemical and biological parameters. Acta Biomater.5(7), 2475–2484 (2009).
   PubMed Web of Science ®Google Scholar
• Chalasani KB , Russell-JonesGJ, YandrapuSK, DiwanPV, JainSK. A novel vitamin B12-nanosphere conjugate carrier system for peroral delivery of insulin. J. Control. Release117(3), 421–429 (2007).
   PubMed Web of Science ®Google Scholar
• Reis CP , RibeiroAJ, VeigaF, NeufeldRJ, DamgéC. Polyelectrolyte biomaterial interactions provide nanoparticulate carrier for oral insulin delivery. Drug Deliv.15(2), 127–139 (2008).
   PubMed Web of Science ®Google Scholar
• Pinto Reis C , NeufeldRJ, RibeiroAJ, VeigaF. Nanoencapsulation II. Biomedical applications and current status of peptide and protein nanoparticulate delivery systems. Nanomed. Nanotechnol. Biol. Med.2(2), 53–65 (2006).
   PubMed Web of Science ®Google Scholar
• Woitiski CB , NeufeldRJ, VeigaF, CarvalhoRA, FigueiredoIV. Pharmacological effect of orally delivered insulin facilitated by multilayered stable nanoparticles. Eur. J. Pharm. Sci.41(3–4), 556–563 (2010).
   PubMed Web of Science ®Google Scholar
• Florence AT . Nanoparticle uptake by the oral route: fulfilling its potential? Drug Discov. Today Technol.2(1), 75–81 (2005).
   PubMedGoogle Scholar
• Sarmento B , RibeiroA, VeigaF, FerreiraD, NeufeldR. Oral bioavailability of insulin contained in polysaccharide nanoparticles. Biomacromolecules8(10), 3054–3060 (2007).
   PubMed Web of Science ®Google Scholar
• Sarmento B , RibeiroA, VeigaF, FerreiraD. Development and characterization of new insulin containing polysaccharide nanoparticles. Coll. Surf. B Biointerfaces53(2), 193–202 (2006).
   PubMed Web of Science ®Google Scholar
• Sarmento B , RibeiroA, VeigaF, SampaioP, NeufeldR, FerreiraD. Alginate/chitosan nanoparticles are effective for oral insulin delivery. Pharm. Res.24(12), 2198–2206 (2007).
   PubMed Web of Science ®Google Scholar
• Sonaje K , Chen Y-J, Chen H-L et al. Enteric-coated capsules filled with freeze–dried chitosan/poly(gamma-glutamic acid) nanoparticles for oral insulin delivery. Biomaterials31(12), 3384–3394 (2010).
   PubMed Web of Science ®Google Scholar
• Sonaje K , Lin K-J, Wang J-J et al. Self-assembled pH-sensitive nanoparticles: a platform for oral delivery of protein drugs. Adv. Func. Mater.20(21), 3695–3700 (2010).
   Web of Science ®Google Scholar
• Sonaje K , Lin K-J, Wey S-P et al. Biodistribution, pharmacodynamics and pharmacokinetics of insulin analogues in a rat model: oral delivery using pH-responsive nanoparticles vs subcutaneous injection. Biomaterials31(26), 6849–6858 (2010).
   PubMed Web of Science ®Google Scholar
• Lin Y -H, Mi F-L, Chen C-T et al. Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery. Biomacromolecules8(1), 146–152 (2007).
   PubMed Web of Science ®Google Scholar
• Shu S , ZhangX, TengD, WangZ, LiC. Polyelectrolyte nanoparticles based on water-soluble chitosan-poly (L-aspartic acid)-polyethylene glycol for controlled protein release. Carbohyd. Res.344(10), 1197–1204 (2009).
   PubMed Web of Science ®Google Scholar
• Makhlof A , TozukaY, TakeuchiH. Design and evaluation of novel pH-sensitive chitosan nanoparticles for oral insulin delivery. Eur. J. Pharm. Sci.42(5), 445–451 (2011).
   PubMed Web of Science ®Google Scholar
• Goycoolea FM , LolloG, Remunan-LopezC, QuagliaF, AlonsoMJ. Chitosan-alginate blended nanoparticles as carriers for the transmucosal delivery of macromolecules. Biomacromolecules10(7), 1736–1743 (2009).
   PubMed Web of Science ®Google Scholar
• Krauland AH , AlonsoMJ. Chitosan/cyclodextrin nanoparticles as macromolecular drug delivery system. Int. J. Pharm.340(1–2), 134–142 (2007).
   PubMed Web of Science ®Google Scholar
• Zhang N , LiJ, JiangWet al. Effective protection and controlled release of insulin by cationic-cyclodextrin polymers from alginate/chitosan nanoparticles. Int. J. Pharm. 393(1–2), 213–219 (2010).
   Web of Science ®Google Scholar
• Prego C , FabreM, TorresD, AlonsoMJ. Efficacy and mechanism of action of chitosan nanocapsules for oral peptide delivery. Pharm. Res.23(3), 549–556 (2006).
   PubMed Web of Science ®Google Scholar
• Azevedo J , SizilioR, BritoMet al. Physical and chemical characterization insulin-loaded chitosan-TPP nanoparticles. J. Therm. Anal. Calorim. 106(3), 685–689 (2011).
   Web of Science ®Google Scholar
• Avadi MR , SadeghiAMM, MohammadpourNet al. Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method. Nanomed. Nanotechnol. Biol. Med. 6(1), 58–63 (2010).
   PubMed Web of Science ®Google Scholar
• Garcia-Fuentes M , TorresD, AlonsoMJ. New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin. Int. J. Pharm.296(1–2), 122–132 (2005).
   PubMed Web of Science ®Google Scholar
• Garcia-Fuentes M , PregoC, TorresD, AlonsoMJ. A comparative study of the potential of solid triglyceride nanostructures coated with chitosan or poly(ethylene glycol) as carriers for oral calcitonin delivery. Eur. J. Pharm. Sci.25(1), 133–143 (2005).
   PubMed Web of Science ®Google Scholar
• Prego C , GarciaM, TorresD, AlonsoMJ. Transmucosal macromolecular drug delivery. J. Control. Release101(1–3), 151–162 (2005).
   PubMed Web of Science ®Google Scholar
• Prego C , TorresD, AlonsoMJ. Chitosan nanocapsules as carriers for oral peptide delivery: effect of chitosan molecular weight and type of salt on the in vitro behaviour and in vivo effectiveness. J. Nanosci. Nanotechnol.6(9–10), 2921–2928 (2006).
   PubMed Web of Science ®Google Scholar
• Vasir JK , TambwekarK, GargS. Bioadhesive microspheres as a controlled drug delivery system. Int. J. Pharm.255(1–2), 13–32 (2003).
   PubMed Web of Science ®Google Scholar
• Gref R , QuellecP, SanchezA, CalvoP, DellacherieE, AlonsoMJ. Development and characterization of CyA-loaded poly(lactic acid):poly(ethylene glycol)PEG micro- and nanoparticles. Comparison with conventional PLA particulate carriers. Eur. J. Pharm. Biopharm.51(2), 111–118 (2001).
   PubMed Web of Science ®Google Scholar
• Belchetz P , HammondP. Mosby´s Colour Atlas and Text of Diabetes and Endocrinology. Elsevier Ltd, Burgos, Spain (2004).
   Google Scholar
• Wong TW . Design of oral insulin delivery systems. J. Drug Target.18(2), 79–92 (2010).
   PubMed Web of Science ®Google Scholar
• Gupta A , JhaKK, AroraR. Insulin durg delivery: strategies and technologies. Pharm. Res.4, 154–168 (2010).
   Google Scholar
• Sabetsky V , EkblomJ. Insulin: a new era for an old hormone. Pharm. Res.61(1), 1–4 (2010).
   Google Scholar
• Thomas F . Advances in insulin delivery systems and devices: beyond the vial and syringe. Insulin1(3), 99–108 (2006).
   Google Scholar
• Peppas NA , KavimandanNJ. Nanoscale analysis of protein and peptide absorption: insulin absorption using complexation and pH-sensitive hydrogels as delivery vehicles. Eur. J. Pharm. Sci.29(3–4), 183–197 (2006).
   PubMed Web of Science ®Google Scholar
• Morishita M , GotoT, NakamuraK, LowmanAM, TakayamaK, PeppasNA. Novel oral insulin delivery systems based on complexation polymer hydrogels: single and multiple administration studies in type 1 and 2 diabetic rats. J. Control. Release110(3), 587–594 (2006).
   PubMed Web of Science ®Google Scholar
• Liu H , TangR, PanWS, ZhangY. Potential utility of various protease inhibitors for improving the intestinal absorption of insulin in rats. J. Pharm. Pharmacol.55(11), 1523–1529 (2003).
   PubMed Web of Science ®Google Scholar
• Agarwal V , ReddyIK, KhanMA. Oral delivery of proteins: effect of chicken and duck ovomucoid on the stability of insulin in the presence of α-chymotrypsin and trypsin. Pharm. Pharmacol. Commun.6(5), 223–227 (2000).
   Google Scholar
• Shah RB , AhsanF, KhanMA. Oral delivery of proteins: progress and prognostication. Crit. Rev. Ther. Drug Carrier Syst.19(2), 135–169 (2002).
   PubMed Web of Science ®Google Scholar
• Li CL , DengYJ. Oil-based formulations for oral delivery of insulin. J. Pharm. Pharmacol.56(9), 1101–1107 (2004).
   PubMed Web of Science ®Google Scholar
• Cox DS , RajeS, GaoHL, SalamaNN, EddingtonND. Enhanced permeability of molecular weight markers and poorly bioavailable compounds across Caco-2 cell monolayers using the absorption enhancer, zonula occludens toxin. Pharm. Res.19(11), 1680–1688 (2002).
   PubMed Web of Science ®Google Scholar
• Karyekar CS , FasanoA, RajeS, LuR, DowlingTC, EddingtonND. Zonula occludens toxin increases the permeability of molecular weight markers and chemotherapeutic agents across the bovine brain microvessel endothelial cells. J. Pharm. Sci.92(2), 414–423 (2003).
   PubMed Web of Science ®Google Scholar
• Eaimtrakarn S , PrasadYVR, OhnoTet al. Absorption enhancing effect of Labrasol on the intestinal absorption of insulin in rats. J. Drug Target. 10(3), 255–260 (2002).
   PubMed Web of Science ®Google Scholar
• Kapitza C , ZijlstraE, HeinemannL, CastelliMC, RileyG, HeiseT. Oral insulin: a comparison with subcutaneous regular human insulin in patients with type 2 diabetes. Diabetes Care33(6), 1288–1290 (2010).
   PubMed Web of Science ®Google Scholar
• Kamei N , MorishitaM, EdaY, IdaN, NishioR, TakayamaK. Usefulness of cell-penetrating peptides to improve intestinal insulin absorption. J. Control. Release132(1), 21–25 (2008).
   PubMed Web of Science ®Google Scholar
• Clement S , DandonaP, StillJG, KosuticG. Oral modified insulin (HIM2) in patients with type 1 diabetes mellitus: results from a phase I/II clinical trial. Metabolism53(1), 54–58 (2004).
   PubMed Web of Science ®Google Scholar
• Hazra P , AdhikaryL, DaveNet al. Development of a process to manufacture PEGylated orally bioavailable insulin. Biotechnol. Prog. 26(6), 1695–1704 (2010).
   PubMed Web of Science ®Google Scholar
• Petrus AK , AllisDG, SmithRP, FairchildTJ, DoyleRP. Exploring the implications of vitamin B12 conjugation to insulin on insulin receptor binding. ChemMedChem4(3), 421–426 (2009).
   PubMed Web of Science ®Google Scholar
• Wood KM , StoneG, PeppasNA. Lectin functionalized complexation hydrogels for oral protein delivery. J. Control. Release116(2), 66–68 (2006).
   Google Scholar
• Makhlof A , WerleM, TozukaY, TakeuchiH. A mucoadhesive nanoparticulate system for the simultaneous delivery of macromolecules and permeation enhancers to the intestinal mucosa. J. Control. Release149(1), 81–88 (2011).
   PubMed Web of Science ®Google Scholar
• Geho WB , GehoHC, LauJR, GanaTJ. Hepatic-directed vesicle insulin: a review of formulation development and preclinical evaluation. Diabetes Technol. Soc.3(6), 1451–1459 (2009).
   PubMedGoogle Scholar
• Woitiski CB , CarvalhoRA, RibeiroAJ, NeufeldRJ, VeigaF. Strategies toward the improved oral delivery of insulin nanoparticles via gastrointestinal uptake and translocation. BioDrugs22(4), 223–237 (2008).
   PubMed Web of Science ®Google Scholar
• Li M -G, Lu W-L, Wang H-C et al. Distribution, transition, adhesion and release of insulin loaded nanoparticles in the gut of rats. Int. J. Pharm.329(1–2), 182–191 (2007).
   PubMed Web of Science ®Google Scholar
• Davaran S , OmidiY, RashidiMRet al. Preparation and in vitro evaluation of linear and star-branched PLGA nanoparticles for insulin delivery. J. Bioact. Compat. Polym. 23(2), 115–131 (2008).
   Web of Science ®Google Scholar
• Xiong XY , LiYP, LiZLet al. Vesicles from pluronic/poly(lactic acid) block copolymers as new carriers for oral insulin delivery. J. Control. Release 120(1–2), 11–17 (2007).
   PubMed Web of Science ®Google Scholar
• Pan Y , LiYJ, ZhaoHYet al. Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo. Int. J. Pharm. 249(1–2), 139–147 (2002).
   PubMed Web of Science ®Google Scholar
• Prego C , TorresD, AlonsoMJ. The potential of chitosan for the oral administration of peptides. Exp. Opin. Drug Deliv.2(5), 843–854 (2005).
   PubMedGoogle Scholar
• Csaba N , Garcia-FuentesM, AlonsoMJ. The performance of nanocarriers for transmucosal drug delivery. Exp. Opin. Drug Deliv.3(4), 463–478 (2006).
   PubMedGoogle Scholar
• de la Fuente M , CsabaN, Garcia-FuentesM, AlonsoMJ. Nanoparticles as protein and gene carriers to mucosal surfaces. Nanomedicine3(6), 845–857 (2008).
   PubMed Web of Science ®Google Scholar
• Krauland AH , GuggiD, Bernkop-SchnurchA. Oral insulin delivery: the potential of thiolated chitosan-insulin tablets on non-diabetic rats. J. Control. Release95(3), 547–555 (2004).
   PubMed Web of Science ®Google Scholar
• Bernkop-Schnurch A . Thiomers: a new generation of mucoadhesive polymers. Adv. Drug Deliv. Rev.57(11), 1569–1582 (2005).
   PubMed Web of Science ®Google Scholar
• Werle M , TakeuchiH, Bernkop-SchnürchA. Modified chitosans for oral drug delivery. J. Pharm. Sci.98(5), 1643–1656 (2009).
   PubMed Web of Science ®Google Scholar
• Rekha MR , SharmaCP. Synthesis and evaluation of lauryl succinyl chitosan particles towards oral insulin delivery and absorption. J. Control. Release135(2), 144–151 (2009).
   PubMed Web of Science ®Google Scholar
• Sonaje K , Lin Y-H, Juang J-H, Wey S-P, Chen C-T, Sung H-W. In vivo evaluation of safety and efficacy of self-assembled nanoparticles for oral insulin delivery. Biomaterials30(12), 2329–2339 (2009).
   PubMed Web of Science ®Google Scholar
• Woitiski CB , SarmentoB, CarvalhoRA, NeufeldRJ, VeigaF. Facilitated nanoscale delivery of insulin across intestinal membrane models. Int. J. Pharm.412(1–2), 123–131 (2011).
   PubMed Web of Science ®Google Scholar
• Varela MC , GuzmanM, MolpeceresJ, del Rosario Aberturas M, Rodriguez-Puyol D, Rodriguez-Puyol M. Cyclosporine-loaded polycaprolactone nanoparticles: immunosuppression and nephrotoxicity in rats. Eur. J. Pharm. Sci.12(4), 471–478 (2001).
   PubMed Web of Science ®Google Scholar
• Graf A , McDowellA, RadesT. Poly(alkycyanoacrylate) nanoparticles for enhanced delivery of therapeutics: is there real potential? Exp. Opin. Drug Deliv.6(4), 371–387 (2009).
   PubMed Web of Science ®Google Scholar
• El-Shabouri MH . Positively charged nanoparticles for improving the oral bioavailability of cyclosporin-A. Int. J. Pharm.249(1–2), 101–108 (2002).
   PubMed Web of Science ®Google Scholar

Websites

• Clinical Trials. www.clinicaltrials.gov (Accessed 25October2011)
   Google Scholar
• ISI Web of Knowledge. www.webofknowledge.com (Accessed 25October2011)
   Google Scholar