Improving stability and release kinetics of microencapsulated tetanus toxoid by co-encapsulation of additives.
OBJECTIVE
Tetanus toxoid (Ttxd) encapsulated in polyester microspheres (MS) for single injection immunization have so far given pulsatile in vitro release and strong immune response in animals, but no boosting effect. This has been ascribed to insufficient toxoid stability within the MS exposed to in vivo conditions over a prolonged time period. This study examined the effect of co-encapsulated putative stabilizing additives.


METHODS
Two different Ttxd were encapsulated in poly(D,L-lactic-co-glycolic acid) (PLGA 50:50) and poly(D,L-lactic acid) (PLA) MS by spray-drying. The influence of co-encapsulated additives on toxoid stability, loading in and release from the MS, was studied by fluorimetry and ELISA.


RESULTS
Co-encapsulated albumin, trehalose and gamma-hydroxypropyl cyclodextrin all improved the toxoid encapsulation efficiency in PLGA 50:50 MS. Albumin increased the encapsulation efficiency of antigenic Ttxd by one to two orders of magnitude. Further, with albumin or a mixture of albumin and trehalose ELISA responsive Ttxd was released over 1-2 months following a pulsatile pattern.


CONCLUSIONS
Optimized Ttxd containing MS may be valuable for a single-dose vaccine delivery system.
Department of Pharmacy, ETH-Zürich.
P
P
Johansen
Y
Y
Men
R
R
Audran
G
G
Corradin
H P
HP
Merkle
B
B
Gander
D002214:Capsules; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D007700:Kinetics; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D008863:Microspheres; D010592:Pharmaceutic Aids / Q000008:administration & dosage* / Q000737:chemistry*; D011091:Polyesters; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000737:chemistry* / Q000276:immunology
D002214:Capsules; D010592:Pharmaceutic Aids; D011091:Polyesters; D011108:Polymers; D013745:Tetanus Toxoid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)