Release of tetanus toxoid from adjuvants and PLGA microspheres: How experimental set-up and surface adsorption fool the pattern
Release of tetanus toxoid from adjuvants and PLGA microspheres: How experimental set-up and surface adsorption fool the pattern
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DOI：
10.1016/s0168-3659(98)00084-4
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发表时间：
1998-12-04
影响因子：
10.8
通讯作者：
Gander, B
中科院分区：
文献类型：
--
作者：
Johansen, P;Corradin, G;Gander, B
经典佐剂明矾和弗氏不完全佐剂（IFA）经常用作设计新佐剂和抗原递送系统的参考，微球（MS）。已提出聚（或乳酸-共-乙醇酸）（PLGA）MS用于在单次注射后体内递送抗原加强剂量。然而，由于常规佐剂的抗原释放动力学通常是未知的，因此，提出PLGA MS的所需抗原释放模式似乎是冒昧的。因此，我们研究了在四个不同的测试系统中从明矾、IFA制剂和MS的破伤风环（Ttxd）体外释放。结果显示，与IFA相比，Ttxd与明矾的结合更强，并且从两种制剂的释放持续3-9天。释放的ELISA应答抗原总量为实际剂量的60-85%。总释放量和释放时间均依赖于Ttxd剂量。此外，Ttxd从佐剂以及从PLGA 50：50 MS的不完全体外释放显示部分是由于实验条件。通常，Ttxd吸附在用于释放测试的玻璃小瓶上，并且还吸附在PLGA 50：50 MS的表面上，从那里释放。总之，观察到的释放速率和释放量依赖于试验系统，证明了体外释放数据的局限性。最后，为了模拟常规的疫苗接种时间表，即通常在时间点0、1、3和12-24个月注射，PLGA MS应在相应的时间点释放抗原剂量，并且释放脉冲应仅持续几天。(C)1998 Elsevier Science B. V.保留所有权利。
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.