Lactic acid triggers, in vitro, thiomersal to degrade protein in the presence of PLGA microspheres.
Microspheres of polymers like poly(lactic-co-glycolic acid) (PLGA) have been studied as a vehicle for controlled release vaccines. They require materials and processes that might change the protein antigenicity. Lactic acid is produced during microsphere degradation that occurs in tandem with protein liberation. In addition, most of the proteins that have been used in microencapsulation studies contain Thimerosal((R))(TM) and this can introduce another undesirable effect for their stability. We demonstrated in vitro that the thiosalycilic acid (TSA), produced after the reduction of TM by lactic acid, reduces the S-S bridge of the previously incubated diphtheric toxoid (Dtxd). This reduction is immediately followed by blocking the two -SH formed by the same TSA molecules. In the light of these conclusions it is necessary now, to reinterpret the in vitro protein degradation-stabilization data in the presence of PLGA microspheres, mainly for those proteins which contain S-S. We propose that all the PLGA microspheres microencapsulation studies and protein structural considerations should be done in the absence of TM as preservative.
Lab. de Microesferas e Lipossomos, C. de Biotecnologia, São Paulo, SP, Brazil.
Jocimara A M
JA
Namur
Célia S
CS
Takata
Ana M
AM
Moro
Mário J
MJ
Politi
P Soares
PS
De Araujo
Iolanda M
IM
Cuccovia
M H Bueno
MH
Da Costa
D004168:Diphtheria Toxoid / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004347:Drug Interactions; D004355:Drug Stability; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011310:Preservatives, Pharmaceutical / Q000737:chemistry*; D013849:Thimerosal / Q000737:chemistry*
D004168:Diphtheria Toxoid; D004337:Drug Carriers; D011108:Polymers; D011310:Preservatives, Pharmaceutical; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013849:Thimerosal; D011100:Polyglycolic Acid; D019344:Lactic Acid