Overcoming oral insulin delivery barriers: application of cell penetrating peptide and silica-based nanoporous composites

  • Huining He
  • Junxiao Ye
  • Jianyong Sheng
  • Jianxin Wang
  • Yongzhuo Huang
  • Guanyi Chen
  • Jingkang Wang
  • Victor C. Yang
Review Article

Abstract

Oral insulin delivery has received the most attention in insulin formulations due to its high patient compliance and, more importantly, to its potential to mimic the physiologic insulin secretion seen in non-diabetic individuals. However, oral insulin delivery has two major limitations: the enzymatic barrier that leads to rapid insulin degradation, and the mucosal barrier that limits insulin’s bioavailability. Several approaches have been actively pursued to circumvent the enzyme barrier, with some of them receiving promising results. Yet, thus far there has been no major success in overcoming the mucosal barrier, which is the main cause in undercutting insulin’s oral bioavailability. In this review of our group’s research, an innovative silica-based, mucoadhesive oral insulin formulation with encapsulated-insulin/cell penetrating peptide (CPP) to overcome both enzyme and mucosal barriers is discussed, and the preliminary and convincing results to confirm the plausibility of this oral insulin delivery system are reviewed. In vitro studies demonstrated that the CPPinsulin conjugates could facilitate cellular uptake of insulin while keeping insulin’s biologic functions intact. It was also confirmed that low molecular weight protamine (LMWP) behaves like a CPP peptide, with a cell translocation potency equivalent to that of the widely studied TAT. The mucoadhesive properties of the produced silica-chitosan composites could be controlled by varying both the pH and composition; the composite consisting of chitosan (25 wt-%) and silica (75 wt-%) exhibited the greatest mucoadhesion at gastric pH. Furthermore, drug release from the composite network could also be regulated by altering the chitosan content. Overall, the universal applicability of those technologies could lead to development of a generic platform for oral delivery of many other bioactive compounds, especially for peptide or protein drugs which inevitably encounter the poor bioavailability issues.

Keywords

insulin cell penetrating peptide mucoadhesive composites oral delivery 

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Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Huining He
    • 1
    • 4
    • 5
  • Junxiao Ye
    • 1
  • Jianyong Sheng
    • 2
  • Jianxin Wang
    • 2
  • Yongzhuo Huang
    • 2
    • 3
  • Guanyi Chen
    • 4
  • Jingkang Wang
    • 1
  • Victor C. Yang
    • 5
    • 6
  1. 1.School of Chemical Engineering and TechnologyTianjin UniversityTianjinChina
  2. 2.Department of Pharmaceutics, School of PharmacyFudan University; Key Laboratory of Smart Drug Delivery, Ministry of Education & PLAShanghaiChina
  3. 3.Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina
  4. 4.School of Environmental Science and EngineeringState Key Laboratory of Engines Tianjin UniversityTianjinChina
  5. 5.Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of PharmacyTianjin Medical UniversityTianjinChina
  6. 6.Department of Pharmaceutical Sciences, College of PharmacyUniversity of MichiganMichiganUSA

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