Active self-healing encapsulation of vaccine antigens in PLGA microspheres.
Active self-healing encapsulation of vaccine antigens in PLGA microspheres.
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DOI：
10.1016/j.jconrel.2012.10.012
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发表时间：
2013-01-10
期刊：
影响因子：
--
通讯作者：
Schwendeman SP
中科院分区：
文献类型：
--
作者：
Desai KG;Schwendeman SP
在此，我们描述了一种简单有效的方法的详细开发，该方法通过在适度温度（10-38 °C）下将预形成的活性自微囊化（SM）PLGA微球在低浓度抗原水溶液中简单混合来将疫苗抗原微囊化在聚（乳酸-共-乙醇酸）（PLGA）中。共包封蛋白质吸附疫苗佐剂和聚合物增塑剂用于“主动”将蛋白质加载到聚合物孔中，并分别在>水合聚合物玻璃化转变温度的温度下促进聚合物自修复。研究了在PLGA中提供疫苗抗原的最佳活性自愈微囊化的微球制剂参数和装载条件。通过制备含不同佐剂（Al（OH）3或磷酸钙）的空白微球，对卵清蛋白（ovalbumin）和破伤风类毒素（TT）疫苗抗原在PLGA微球中的主动自愈包封进行了调节。发现Al（OH）3-PLGA微球中疫苗抗原的活性负载：a）随着Al（OH）3负载量的增加而成比例地增加B）当内相Al（OH）3/海藻糖与外相油的比例为1 mL时，微球的粒径分别大于0.2 mL和63 μm时，微球的孔径减小;和c）PLGA浓度和初始孵育（加载）温度的变化可忽略不计。包封的蛋白质吸附Al（OH）3在PLGA微球导致抑制PLGA孔的自愈，然后克服了提高聚合物链的流动性，这反过来又是通过在PLGA中共掺入疏水增塑剂。发现在PLGA中的制造工艺不稳定的TT的活性自修复微囊化：a）抑制微粉化和有机溶剂诱导的TT降解，B）改善抗原负载（1.4-1.8重量% TT）和囊化效率（~ 97%），c）提供抗原在聚合物中的几乎均匀的分布和稳定化，和d）提供抗原TT的改善的体外受控释放。
Herein, we describe the detailed development of a simple and effective method to microencapsulate vaccine antigens in poly(lactic-co-glycolic acid) (PLGA) by simple mixing of preformed active self-microencapsulating (SM) PLGA microspheres in a low concentration aqueous antigen solution at modest temperature (10-38 °C). Co-encapsulating protein-sorbing vaccine adjuvants and polymer plasticizers were used to “actively” load the protein in the polymer pores and facilitate polymer self-healing at temperature > hydrated polymer glass transition temperature, respectively. The microsphere formulation parameters and loading conditions to provide optimal active self-healing microencapsulation of vaccine antigen in PLGA was investigated. Active self-healing encapsulation of two vaccine antigens, ovalbumin and tetanus toxoid (TT), in PLGA microspheres was adjusted by preparing blank microspheres containing different vaccine adjuvant (aluminum hydroxide (Al(OH)3) or calcium phosphate). Active loading of vaccine antigen in Al(OH)3-PLGA microspheres was found to: a) increase proportionally with an increasing loading of Al(OH)3 (0.88-3 wt%) and addition of porosigen, b) decrease when the inner Al(OH)3/trehalose phase to 1 mL outer oil phase and size of microspheres was respectively > 0.2 mL and 63 μm, and c) change negligibly by PLGA concentration and initial incubation (loading) temperature. Encapsulation of protein sorbing Al(OH)3 in PLGA microspheres resulted in suppression of self-healing of PLGA pores, which was then overcome by improving polymer chain mobility, which in turn was accomplished by coincorporating hydrophobic plasticizers in PLGA. Active self-healing microencapsulation of manufacturing process-labile TT in PLGA was found to: a) obviate micronization- and organic solvent-induced TT degradation, b) improve antigen loading (1.4-1.8 wt% TT) and encapsulation efficiency (~ 97%), c) provide nearly homogeneous distribution and stabilization of antigen in polymer, and d) provide improved in vitro controlled release of antigenic TT.
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影响因子：
16.6
作者：
Reinhold, Samuel E.;Desai, Kashappa-Goud H.;Zhang, Li;Olsen, Karl F.;Schwendeman, Steven P.
通讯作者：
Schwendeman, Steven P.
影响因子：
3.7
作者：
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通讯作者：
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5.5
作者：
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10.8
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Pedraz, JL
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5.8
作者：
Murillo, M;Gamazo, C;Blanco-Príeto, MJ
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Blanco-Príeto, MJ