Abstract:
:The development of a single-dose tetanus vaccine based on Poly(Lactic acid) (PLA) or Poly(Lactide-co-Glycolide) (PLGA) microspheres has been complicated due to the instability of tetanus toxoid (TT) inside these systems. Herein we report an attempt to re-design PLGA microspheres by co-encapsulating TT in the dry solid state together with potential protein stabilizers, such as trehalose, bovine serum albumin, alginate, heparin, dextran or poloxamer 188 and by using an appropriate microencapsulation technique. These newly developed PLGA microspheres were able to release in vitro antigenically active TT for at least 5 weeks, the amount released being highly dependent on the stabilizing excipient used. More specifically, results showed that dextran and heparin provided a particularly stabilizing environment for TT inside the microspheres during the polymer degradation process. The efficacy of this strategy was demonstrated by the high, long lasting titers of neutralizing antibodies achieved after in vivo administration of dextran-containing microspheres with a small amount of alum-adsorbed TT, as compared to the commercial adsorbable tetanus vaccine. These findings suggest that future developments in the area of vaccinology depend on ability to combine a detailed knowledge of the microencapsulation technology with a rational choice of stabilizing excipient or combination of excipients.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Sánchez A,Villamayor B,Guo Y,McIver J,Alonso MJdoi
10.1016/s0378-5173(99)00178-7keywords:
subject
Has Abstractpub_date
1999-08-20 00:00:00pages
255-66issue
2eissn
0378-5173issn
1873-3476pii
S0378517399001787journal_volume
185pub_type
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