Release of tetanus toxoid from adjuvants and PLGA microspheres: How experimental set-up and surface adsorption fool the pattern

被引:26
作者
Johansen, P
Corradin, G
Merkle, HP
Gander, B
机构
[1] ETH Zurich, Dept Pharm, CH-8057 Zurich, Switzerland
[2] Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland
关键词
antigen delivery; PLGA microspheres; tetanus toxoid; toxoid adsorption; adjuvants; release models;
D O I
10.1016/S0168-3659(98)00084-4
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The classical adjuvants alum and Freund's Incomplete Adjuvant (IFA) are frequently used as references for the design of new adjuvants and antigen delivery systems, e.g., microspheres (MS). Poly(or-lactic-co-glycolic acid) (PLGA) MS have been proposed for delivering antigen booster doses in vivo after a single injection. However, as antigen release kinetics from conventional adjuvants are generally unknown, it appears presumptuous to propose a desired antigen release pattern from PLGA MS. Therefore, we have studied the tetanus toroid (Ttxd) in vitro release from alum, IFA formulations and MS in four different test systems. The results showed a stronger Ttxd association to alum than to IFA, and the release from both formulations lasted between 3-9 days. The total of ELISA-responsive antigen released was 60-85% of the actual dose. Both the total amount and the prolongation of release depended on the Ttxd dose. Furthermore, the incomplete in vitro release of Ttxd from the adjuvants and also from PLGA 50:50 MS was shown to be partly due to experimental conditions. Typically, Ttxd adsorbed on the glass vials used for the release test and also on the surface of the PLGA 50:50 MS, where from it was released. In conclusion, the test system depending rate and quantity of release observed evidence the limitations of in vitro release data. Finally, for mimicking conventional vaccination schedules, i.e. injections typically at time points 0, 1, 3, and 12-24 months, PLGA MS should release antigen doses at the corresponding time points, and the release pulse should only last for a few days. (C) 1998 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:209 / 217
页数:9
相关论文
共 26 条
[1]   IMMUNE-RESPONSE TO NASAL DELIVERY OF ANTIGENICALLY INTACT TETANUS TOXOID ASSOCIATED WITH POLY(L-LACTIC ACID) MICROSPHERES IN RATS, RABBITS AND GUINEA-PIGS [J].
ALMEIDA, AJ ;
ALPAR, HO ;
BROWN, MRW .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1993, 45 (03) :198-203
[2]  
ALPAR HO, 1994, EUR J PHARM BIOPHARM, V40, P198
[3]   ADSORPTION OF SALMON-CALCITONIN TO PLGA MICROSPHERES [J].
CALIS, S ;
JEYANTHI, R ;
TSAI, T ;
MEHTA, RC ;
DELUCA, PP .
PHARMACEUTICAL RESEARCH, 1995, 12 (07) :1072-1076
[4]   Stabilization of tetanus toxoid in poly(DL-lactic-co-glycolic acid) microspheres for the controlled release of antigen [J].
Chang, AC ;
Gupta, RK .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1996, 85 (02) :129-132
[5]   TESTING OF IN-VITRO DISSOLUTION BEHAVIOR OF MICROPARTICULATE DRUG-DELIVERY SYSTEMS [J].
CONTI, B ;
GENTA, I ;
GIUNCHEDI, P ;
MODENA, T .
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 1995, 21 (10) :1223-1233
[6]   Single dose, polymeric, microparticle based vaccines: The influence of formulation conditions on the magnitude and duration of the immune response to a protein antigen [J].
Coombes, AGA ;
Lavelle, EC ;
Jenkins, PG ;
Davis, SS .
VACCINE, 1996, 14 (15) :1429-1438
[7]   FOURIER-TRANSFORM INFRARED SPECTROSCOPIC INVESTIGATION OF PROTEIN STABILITY IN THE LYOPHILIZED FORM [J].
COSTANTINO, HR ;
GRIEBENOW, K ;
MISHRA, P ;
LANGER, R ;
KLIBANOV, A .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 1995, 1253 (01) :69-74
[8]   Adsorption determines in-vitro protein release rate from biodegradable microspheres: Quantitative analysis of surface area during degradation [J].
Crotts, G ;
Sah, H ;
Park, TG .
JOURNAL OF CONTROLLED RELEASE, 1997, 47 (01) :101-111
[9]   INFLUENCE OF SURFACTANTS UPON PROTEIN PEPTIDE ADSORPTION TO GLASS AND POLYPROPYLENE [J].
DUNCAN, MR ;
LEE, JM ;
WARCHOL, MP .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1995, 120 (02) :179-188
[10]   Thermodynamic approach to protein microencapsulation into poly(D,L-lactide) by spray drying [J].
Gander, B ;
Johansen, P ;
NamTran, H ;
Merkle, HP .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1996, 129 (1-2) :51-61