6/5/13 Injectable Nano-Network for Glucose-Mediated Insulin Delivery

Paper:

Injectable Nano-Network for Glucose-Mediated Insulin Delivery

Zhen Gu,

Alex A. Aimetti,

Qun Wang,

Tram T. Dang, Yunlong Zhang, Omid Veiseh,

Hao Cheng, Robert S. Langer, and Daniel G. Anderson†

ACS Nano, 7(5) (2013) 4194
Keywords: diabetes treatment, nano network, nanoparticles, drug delivery, nanoparticle self-assembly

I didn't summarize all of this paper, because the last half of the paper was more about the drug interaction instead of the nano-network.

Dead Body: Open-loop insulin/glucose control is tough for the patient.  Semi-automated control is a little better (with blood glucose monitor and external insulin infusor), but problems are guaranteed accurate signal feedback and preventing biofouling. Closed loop systems can be better, though bulk hydrogels are slow and membranes aren't strong enough to limit release of insulin.

Prior work: See Citation 4 for something that might be really interesting.

Solution: Use biocompatible matrix of modified dextran which degrades in acid, and releases insulin

Background: GOx catalyzes glucose to gluconic acid and changes the pH of the solution.  This pH change can be recognized by certain biosystems to allow for tailored release of insulin

What are the most interesting results: 

• NPs, coated with either positively-charged chitosan or negatively-charged alginate, both polysaccharides, will self assemble! The charge makes them for a high-surface area, nano gel-like network.
• Fully coated NPs were 340 and 293 nm, for chitosan and alginate NPs respectively.
• The structure broke down really well in response to hyperglycemic solution

What are the most interesting discussions: 

• the nano network is stabalized in equilibrium from attractive (agglomeration) and repulsion (pores) energy.
• 
  

Materials used: 

NPs: 4 components 1) acid-degradeable polymer matrix, 2) polyelectroyte-based surface coatings, 3) encapsulated glucose-specific enzymes (GOx and catalase) and 4) insulin.

How this applies to my work:

• creating nanonetworks can be pretty important for closed-loop drug delivery systems.
• The sizes of the NPs (100s of nm) is much larger than what I deal with, but I wonder if going smaller is better.  
• Is there an imagine technique that can be used to better determine the breakdown of the NP coatings and therefore understand the drug release better.
• Why do you need the nanonetwork?  why can't you just have the coated NPs?
• Is it possible that some of these materials could be loaded into a different matrix which will magnify the reaction rate?  
• It seems like the lump from the nano-network was quite large.  In what way can the size be reduced?

Applications:

Cited - treating diabetes 

My own - other forms on drug delivery