title: Controlled release of dexamethasone from PLGA microspheres embedded within polyacid-containing PVA hydrogels.
abstract: The development of zero-order release systems capable of delivering drug(s) over extended periods of time is deemed necessary for a variety of biomedical applications. We hereby describe a simple, yet versatile, delivery platform based on physically cross-linked poly(vinyl alcohol) (PVA) microgels (cross-linked via repetitive freeze/thaw cycling) containing entrapped dexamethasone-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres for controlled delivery over a 1-month period. The incorporation of polyacids, such as humic acids, Nafion, and poly(acrylic acid), was found to be crucial for attaining approximately zero-order release kinetics, releasing 60% to 75% of dexamethasone within 1 month. Microspheres alone entrapped in the PVA hydrogel resulted in negligible drug release during the 1-month period of investigation. On the basis of a comprehensive evaluation of the structure-property relationships of these hydrogel/microsphere composites, in conjunction with their in vitro release performance, it was concluded that these polyacids segregate on the PLGA microsphere surfaces and thereby result in localized acidity. These surface-associated polyacids appear to cause acid-assisted hydrolysis to occur from the surface inwards. Such systems show potential for a variety of localized controlled drug delivery applications such as coatings for implantable devices.
authors.affiliation: Department of Chemistry, Institute of Materials Science, University of Connecticut, 97 N Eagleville Road, Storrs, CT 06269, USA.
authors.forename: Isabela
authors.initials: I
authors.lastname: Galeska
authors.forename: Tae-Kyoung
authors.initials: TK
authors.lastname: Kim
authors.forename: Siddhesh D
authors.initials: SD
authors.lastname: Patil
authors.forename: Upkar
authors.initials: U
authors.lastname: Bhardwaj
authors.forename: Debjit
authors.initials: D
authors.lastname: Chatttopadhyay
authors.forename: Fotios
authors.initials: F
authors.lastname: Papadimitrakopoulos
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Burgess
mesh_terms: D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage*; D005615:Freezing; D020100:Hydrogels; D006868:Hydrolysis; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011142:Polyvinyl Alcohol; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D020100:Hydrogels; D011108:Polymers; C062364:polyvinyl alcohol hydrogel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; D011142:Polyvinyl Alcohol