Lipases and Phospholipases in Drug Development (From Biochemistry to Molecular Pharmacology) || Rational Design of a Liposomal Drug Delivery System Based on Biophysical Studies of Phospholipase A2 Activity on Model Lipid Membranes
✍ Scribed by Müller, Günter; Petry, Stefan
- Publisher
- Wiley-VCH Verlag GmbH & Co. KGaA
- Year
- 2005
- Tongue
- German
- Weight
- 273 KB
- Edition
- 1
- Category
- Article
- ISBN
- 3527306773
No coin nor oath required. For personal study only.
✦ Synopsis
Secretory phospholipase A 2 (sPLA 2 ) belongs to a family of small interfacially active enzymes that catalyze the hydrolysis of phospholipids, yielding lysolipids and fatty acids. sPLA 2 is found in snake and bee venom and also in inflammatory and cancerous tissue. It is mainly active on organized lipid substrates such as micelles and lipid membranes, and its hydrolytic activity is moreover strongly influenced by the physical properties of the supramolecular lipid substrate. Systematic model studies of the activity of sPLA 2 on lipid-membrane substrates of different compositions have provided insight into the biophysical mechanisms of sPLA 2 activation. In particular, combined theoretical and experimental model studies have revealed an intimate relationship between the activity of sPLA 2 and the formation of small-scale lipid domains in the lipid membrane substrate. This has been used to design and develop a principle for liposomal drug targeting, release, and absorption that is based on the presence of high levels of sPLA 2 activity in certain diseased target tissue.