We have a sugar-PEG-DOX drug carrier which is water soluble and forms micelle structure whose size is around 60 nm. DOX is bound to PEG block via an enzymaticly cleavable linkage. Our problem is since the polymer forms a micelle structure in aqua system, the enzyme, which will break the bound and leads to releasing of the DOX is not efficient because of limited enzyme can reach the core part of the micelle. Which means the interaction between the enzyme and the linkage is less. My question is how I can increase enzymatic cleavage in our carrier system. I'm open to any suggestion.
Thanks.
Depending in the pH, and th pI of the enzyme you can add (ou to ,1 mole fraction) of a surfactant with a charge opposite to that of the enzyme. This addition will: a) increase the head group distance and b) the enzyme affinity for the micelle. Several charged lysolipids with + or - charges are available.
You may tailor a mixte micelle comprissing your targeted amphiphile glycoligand and another different amphiphile (a simpler one). In this way the micelle will show more flexibility, and fluidity, thus allowing the enzyme to get into the core of the micelle more easily. Then, you may study the more suitable ratio of amphiphiles for a higher cleavage and activity.
Thanks a lot all valuable responds. Prof. Hernan, can you suggest any paper for your solution or in a similar manner paper? Actually I was thinking to add some DOPE, etc. Prabhu, do you remember a paper that used for enzyme DOPE/DOPC interaction?
Thanks.
Yuan, you can get info from our papers:
http://www.bme.umich.edu/labs/centlab/documents/pub27.pdf
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