A potential approach for decreasing the burst effect of protein from PLGA microspheres.
A central issue in controlled delivery of therapeutics from biodegradable microspheres is the immediate burst of drug release upon injection. This burst is often observed with microsphere systems made by the double emulsion (w/o/w) technique, and may be prevented by improving the drug distribution throughout the polymer matrix. To this end, protein and polymer (poly-lactide-co-glycolide or PLGA) were dissolved within the same solvent system, and micron-sized microspheres were created from this solution by spontaneous emulsification. Improved protein loading was achieved by ion-pairing the protein with charged surfactants to increase solubility in the single-phase solvent system. Both in vitro and in vivo results showed a much diminished burst: compared to microspheres made by double emulsion, it was reduced over 10-fold.
Fu
Karen
K
Harvard-MIT Division of Health Sciences and Technology, E25-342, MIT, 45 Carleton St, Cambridge, Massachusetts 02139, USA.
Harrell
Roy
R
Zinski
Kim
K
Um
Christina
C
Jaklenec
Ana
A
Frazier
Jan
J
Lotan
Noah
N
Burke
Paul
P
Klibanov
Alexander M
AM
Langer
Robert
R
D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics*; D011506:Proteins / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003692:Delayed-Action Preparations; D011108:Polymers; D011506:Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid