Artificial polymeric cells for targeted drug delivery.
Selectins are optimal biological molecules for targeted delivery of therapeutic agents because of their localized and carefully regulated expression in several human diseases, and their highly specific interactions with their counter receptors. In this study, we describe a targeted delivery system that can potentially deliver anti-inflammatory drug to sites of chronic inflammation using Poly(lactic-co-glycolic acid) (PLGA) and selectin-ligand chemistry. Biotinylated-sialyl Lewis(x) (sLe(x)), a carbohydrate that serves as a ligand to selectins, was attached to the surface of avidin-linked PLGA microspheres. These carbohydrate-coated microspheres mimic the adhesive behavior of leukocytes on selectins in flow chambers, displaying slow rolling under flow. The rolling velocity of these artificial leukocytes is similar to that displayed by leukocytes rolling on P- or E-selectin coated surfaces. We can tune rolling velocity, and hence residence time of capsules on surfaces, by changing the density of sialyl Lewis(x) on the microsphere surfaces. Therefore, we have made a targeted drug delivery vehicle that mimics the adhesive properties of leukocytes and is biodegradable.
Eniola
A Omolola
AO
Department of Chemical Engineering and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104-6316, USA.
Hammer
Daniel A
DA
D016503:Drug Delivery Systems / Q000379:methods*; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D007962:Leukocytes / Q000737:chemistry / Q000187:drug effects; D008863:Microspheres; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D019087:Selectins / Q000008:administration & dosage* / Q000737:chemistry
D011108:Polymers; D019087:Selectins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid