Biphasic release of protein from polyethylene glycol and polyethylene glycol/modified dextran microspheres

Abstract

Dextrans show great promise for delivery of therapeutic agents. Dextran acetates (DAs) were synthesized with increasing degrees of substitution (DA1 < DA2 < DA3) by the reaction of the polysaccharide dextran (70 kDa) with acetic anhydride. A series of polyethylene glycol (PEG)/DA microspheres were prepared and tested with bovine serum albumin (BSA) functioning as a model protein. Particle size (0.74-0.85 μm) and encapsulation efficiency (56-70%) increased with the degree of substitution along with a slower release rate of protein from PEG/DA microspheres. Time to release 90% of protein rose from 31 to 118 min. Percentage of BSA released from PEG and PEG/DA3 microspheres with time (min) was modeled mathematically [Y(PEG) = 100(1 - e(-0.12t)); Y(PEG/DA3) = 100(1 - e(-0.024t))] to predict cumulative delivery from mixtures in vitro over a period of hours when constrained to a target level at 30 min. The system is examined for potential application in thrombolytic therapy.

Recent Strategies for the Immobilization of Therapeutic Enzymes

“…However, its immobilization with dextran hydrogels could improve its delivery and eliminate allergic reactions. In addition, to solve the inactivation of enzymes in organic solvents, dextran microspheres could be used, which could be formed in a poly(ethylene glycol) (PEG) water system [ 29 , 30 ].…”