共聚比不同的两种聚乳酸-聚羟基乙酸共聚物材料生物相容性观测

背景：近年来，α-羟基酸及其衍生物合成的脂肪族聚酯，如聚乳酸、聚羟基乙酸等已广泛用于周围神经组织工程的支架材料研究，这种支架有可能克服因自体神经移植缺乏及供区的永久性失神经支配以及供受区神经匹配等问题，提高神经诱导作用。 目的：对共聚比为（85：15）及（50：50）的聚乳酸-聚羟基乙酸共聚物材料的生物相容性及神经再生诱导作用进行对比观测。 设计：分组观察对比实验。 单位：解放军第三军医大学附属新桥医院骨科。 材料：清洁级健康成年Wistar大鼠66只，雌雄不拘，体质量180～200kg；共聚比为（85：15）及（50：50）的聚乳酸-聚羟基乙酸共聚物。方法：实验于2001-11／2002-12在第三军医大学大坪医院野战外科研究所6室，创伤、烧伤与复合伤国家重点实验室完成。①许旺细胞的培养及与聚乳酸-聚羟基乙酸共聚物膜的共培养观察：将培养的许旺细胞接种于聚乳酸-聚羟基乙酸共聚物膜上，应用扫描电镜观察细胞在共聚物膜上的生长情况。②聚乳酸-聚羟基乙酸共聚物膜材料肌肉包埋组织学观察：取Wistar大鼠15只，实验动物按随机数字法分以1，2,4，8和12周为时相点分为5组，每组3只。将共聚物材料（85：15）裁剪成10mm&;#215;5mm&;#215;0．3mm的膜，植入大鼠椎旁肌内，各时相点切取包含聚乳酸-聚羟基乙酸共聚物膜在内的周围组织进行苏木精-伊红染色。③聚乳酸-聚羟基乙酸共聚物管材料样品桥接大鼠坐骨神经缺损预实验：取Wistar大鼠51只，分为共聚物85：15管组、共聚物50：50管组和硅胶管组，各组以2，4．6，8和12周为观察时相点，除12周为5只太鼠外，其余各时相点均为3只大鼠。于各时相点对各组材料进行大体观察及12周对大鼠进行再生神经运动传导速度测定，并取材桥接管中新生神经中段进行甲苯胺蓝染色，光镜观察。 主要观察指标：主要结局：①大鼠肌肉包埋条件下聚乳酸-聚羟基乙酸共聚物组织学观察。②坐骨神经缺损桥接大鼠实验模型应用组织学及神经电生理学检测聚乳酸-聚羟基乙酸共聚物管神经诱导作用。次要结局：许旺细胞和共聚物共培养条件下许旺细胞的生长行为观察。 结果：66只大鼠均进入结果分析。①大鼠肌肉包埋条件下聚乳酸-聚羟基乙酸共聚物组织学观察结果：聚乳酸-聚羟基乙酸共聚物早期诱发以淋巴细胞及成纤维细胞为主的轻度的非特异性炎性反应，持续到10～12周时基本消退。②许旺细胞的培养及与聚乳酸-聚羟基乙酸共聚物膜的共培养观察结果：许旺细胞在聚乳酸-聚羟基乙酸共聚物膜上能良好的生长并发生增殖。③大鼠体内神经桥接实验结果：大体观察：硅胶管促发有明显的纤维组织增生，而形成包囊包裹于管壁，而两种聚乳酸-聚羟基乙酸共聚物管组未见类似现象；12周再生神经运动传导速度聚乳酸-聚羟基乙酸共聚物85：15管组与硅胶管组无显著差别[（17．03&;#177;0．66），（17．15&;#177;0．76）m／s，P〉0．05]；共聚物85：15管组髓鞘厚度、神经纤维直径、轴突数及神经组织面积比与硅胶管组均无显著差别[（0.45&;#177;0．16）μm，（3．96&;#177;1．73）μn，（10135&;#177;1053）个／mm^2，（23．4&;#177;2．7）％比（0．45&;#177;0．19）μm，（4．07&;#177;1.86）μm，（9879&;#177;1491）个／mm^2，（23．6&;#177;3．1）％，P〉0．05];而聚乳酸-聚羟基乙酸共聚物（50：50）管体内神经桥接4周时即出现破裂，不能为坐骨神经桥接提供良好的支持作用。 结论：与硅胶管及聚乳酸-聚羟基乙酸共聚物（50：50）相比，聚乳酸-聚羟基乙酸共聚物（85：15）是一种异物反应小、生物相容性佳，生物降解速率合适的周围神经组织工程材料。     

新型生物可降解材料聚乳酸凝胶的生物相容性

目的：研究新型生物可降解材料聚乳酸凝胶的生物相容性，为此种材料的应用提供生物学依据。方法：实验于2002—11／2003—02在四川大学华西医院移植免疫实验室和动物实验外科完成。通过动物急性毒性试验、溶血试验、遗传毒性试验、肌腱鞘管内及硬膜外长期植入试验测定材料的动物毒性；并通过细胞毒性测定、细胞与材料混合培养，综合评价新材料的生物相容性。结果：聚乳酸凝胶注射入小鼠无急性毒性；材料浸提液无溶血反应(溶血率为0．22％)及遗传毒性(微核率为0．24％)；材料在动物体内长期埋植后局部和全身各器官无组织损伤，局部无明显粘连；材料浸提液(1000，500，100g／L)的细胞毒性及分级与阴性对照差异无显著性意义(P&;gt;0．05)，材料与细胞的混合培养中细胞生长良好。结论：聚乳酸凝胶具有良好的生物相容性。     

新型生物可降解材料聚乳酸凝胶的生物相容性

目的:研究新型生物可降解材料聚乳酸凝胶的生物相容性,为此种材料的应用提供生物学依据。方法:实验于2002-11/2003-02在四川大学华西医院移植免疫实验室和动物实验外科完成。通过动物急性毒性试验、溶血试验、遗传毒性试验、肌腱鞘管内及硬膜外长期植入试验测定材料的动物毒性;并通过细胞毒性测定、细胞与材料混合培养,综合评价新材料的生物相容性。结果:聚乳酸凝胶注射入小鼠无急性毒性;材料浸提液无溶血反应(溶血率为0.22%)及遗传毒性(微核率为0.24%);材料在动物体内长期埋植后局部和全身各器官无组织损伤,局部无明显粘连;材料浸提液(1000,500,100g/L)的细胞毒性及分级与阴性对照差异无显著性意义(P>0.05),材料与细胞的混合培养中细胞生长良好。结论:聚乳酸凝胶具有良好的生物相容性。     

聚乳酸-聚羟乙酸/磷酸三钙的细胞生物相容性研究

目的:采用骨髓基质细胞检测聚乳酸-聚羟乙酸/磷酸三钙(PLGATCP)材料的细胞生物相容性,筛选细胞组织工程的载体材料。方法:利用骨髓基质细胞在体外接种于PLGA/TCP材料,并与PLGA/TCP材料浸提液共培养,进行形态学观察、细胞增殖及酶学检测。结果:骨髓基质细胞能在PLGA/TCP材料上贴附、繁殖,其生长及功能不受影响。结论PLGA/TCP材料具有良好的细胞生物相容性,能作为细胞组织工程种子细胞的载体材料。     

组织工程人工神经诱导管的制作及其生物相容性观测

目的：观测聚乳酸-聚羟基乙酸共聚物[Poly(DL-lactide-co-glycolide)，PLGA]管生物相容性及其神经再生诱导作用。方法：采用肌肉包埋、雪旺细胞直接接种以及坐骨神经缺损桥接预实验的方法观察两种构成比不同的PLGA管[(85：15)或(50：50)]的生物相容性及其神经再生诱导作用。结果:①肌肉包埋条件下。PLGA早期诱发以淋巴细胞及成纤维细胞为主的轻度的非特异性炎性反应，持续到10-12周时基本消退。②采用细胞直接接种的方法，观察到雪旺细胞在PLGA膜上能良好的生长并发生增殖。③体内神经桥接情况下，硅胶管促发有明显的纤维组织增生，而形成包囊包裹于管壁，而两种PLGA管组未见类似现象。④与硅胶管组相似。PLGA(85：15)管能够顺利完成坐骨神经缺损桥接作用，再生神经电生理及组织学评价显示两组无明显差异，PLGA(50：50)管体内神经桥接4周时即出现破裂，不能为坐骨神经桥接提供良好的支持作用。结论：与硅胶管及PLGA(50：50)相比，PLGA(85：15)是一种异物反应生物相容性佳，生物降解速率合适的周围神经组织工程材料。     

三维支架材料外消旋聚乳酸复合藻酸钙的生物相容性观察

目的:观察外消旋聚乳酸(PDLLA)复合藻酸钙(CAG)制备的三维支架材料的组织相容性、细胞相容性,为进一步改善材料性能提供实验依据。方法:体外大鼠成骨细胞与PDLLA、PDLLA/CAG支架材料联合培养,倒置显微镜、环境扫描电镜观察细胞黏附情况,MTT法分析细胞增殖情况;将支架材料植入大鼠肌袋中,观察局部伤口情况,术后2,4,8,12周行组织学观察。结果:复合支架材料在细胞贴壁时间和细胞活性方面均较单纯支架优良;两种支架材料在体内均无明显炎症反应。MTT法测定结果显示:随着培养时间的延长,各组细胞数量都明显增加,各时间点PDLLA组细胞数高于对照组,差异有显著性意义(t=-285.091,-154.681,-72.794,-81.306,P<0.01);PDLLA/CAG组细胞数高于PDLLA组,差异有显著性意义(t=-297.156,-167.687,-84.900,-103.103,P<0.01)。结论:PDLLA/CGA是一种具有良好生物相容性的支架材料,有望在骨组织工程中得到广泛应用。     

聚乳酸-聚羟乙酸／磷酸三钙薄膜预防屈肌腱粘连的实验

目的：探讨在屈肌腱损伤修复后应用和不应用聚乳酸-聚羟乙酸／磷酸三钙薄膜包裹两种情况下，术后不同时期屈肌腱的粘连情况和聚乳酸-聚羟乙酸／磷酸三钙薄膜在肌腱愈合过程中的作用。方法：实验于2004-03／10在东南大学修复重建外科研究所实验室进行。选取健康成熟的三黄鸡40只，以右足第2，3趾深屈肌腱横断后修复作为肌腱粘连的动物模型，取右足第2趾为实验趾、第3趾为对照趾。聚乳酸-聚羟乙酸／磷酸三钙薄膜包裹，术后3，4，8周分别取材。通过生物力学、大体观察、组织学及扫描电镜检查，观测肌腱愈合情况、与周围组织的粘连情况、屈趾功能及假鞘结构。结果：进入结果分析的实验鸡39只。①实验趾肌腱的屈趾功能明显优于对照趾[术后3周：（10．53&;#177;1．07），（7．78&;#177;0．37）mm，术后4周：（14．96&;#177;1.51），（9．37&;#177;1．35）mm，术后8周：（19．93&;#177;0．81），（11．47&;#177;0．15）mm，P〈0．05]。②大体观察实验趾在各时间段肌腱与腱周组织的粘连均较对照趾轻，肌腱为内源性愈合，并形成具有正常滑膜A、B型细胞的假鞘结构，与肌腱间有间隙。结论：聚乳酸-聚羟乙酸／磷酸三钙薄膜通过刺激周围组织形成假鞘，阻止来自腱周的粘连，且不影响肌腱正常愈合，是较理想的预防肌腱粘连材料。     

组织工程人工神经诱导管的制作及其生物相容性观测

目的观测聚乳酸-聚羟基乙酸共聚物[Poly(DL-lactide-co-glycolide),PLGA]管生物相容性及其神经再生诱导作用。方法采用肌肉包埋、雪旺细胞直接接种以及坐骨神经缺损桥接预实验的方法观察两种构成比不同的PLGA管[(85∶15)或(50∶50)]的生物相容性及其神经再生诱导作用。结果①肌肉包埋条件下,PLGA早期诱发以淋巴细胞及成纤维细胞为主的轻度的非特异性炎性反应,持续到10～12周时基本消退。②采用细胞直接接种的方法,观察到雪旺细胞在PLGA膜上能良好的生长并发生增殖。③体内神经桥接情况下,硅胶管促发有明显的纤维组织增生,而形成包囊包裹于管壁,而两种PLGA管组未见类似现象。④与硅胶管组相似,PLGA(85∶15)管能够顺利完成坐骨神经缺损桥接作用,再生神经电生理及组织学评价显示两组无明显差异,PLGA(50∶50)管体内神经桥接4周时即出现破裂,不能为坐骨神经桥接提供良好的支持作用。结论与硅胶管及PLGA(50∶50)相比,PLGA(85∶15)是一种异物反应生物相容性佳,生物降解速率合适的周围神经组织工程材料。     

家兔骨髓基质细胞培养后与载体聚乳酸-聚乙醇酸复合的相容性

目的：建立一套体外分离培养骨髓基质干细胞的方法，观察骨髓基质细胞的形态和生长规律，检测与载体聚乳酸-聚乙醇酸复合的细胞相容性。 方法：实验于2004-10／2005-04在解放军第四军医大学唐都医院骨实验室完成。选取健康30d龄家兔40只，取幼兔长骨骨髓进行培养，观察其传代细胞生长特性和生长曲线。应用组织培养技术，对兔骨髓基质干细胞和聚乳酸-聚乙醇酸体外联合培养，相差显微镜观察和扫描电镜观察细胞生长情况。 结果：实验纳入家兔40只，全部进入结果分析。①骨髓基质细胞不同接种时间的形态学观察：接种24h后可见大量密集的造血系细胞，有少量散在分布的贴壁细胞，呈多角形、短梭形；第3天可见形态各异、大小不一的贴壁细胞；第7天数量加速生长，己形成成纤维细胞集落，大部分细胞呈梭形，少部分呈多角形；第12天细胞融合成单层，从整体看大多数细胞沿胞体长轴呈有序排列。②骨髓基质细胞接种72h后扫描电镜观察结果：早期可见培养板内细胞增多，并向聚乳酸-聚乙醇酸材料移行贴附于材料周边，部分细胞直接贴附于材料表面，随复合培养时间的延长而增多，细胞形态多为梭形及三角形，无细胞衰老及异常分裂现象。 结论：兔骨髓基质细胞在体外培养条件下，早期生长性状稳定，增殖速度快，适应性强，可作为骨组织工程学的种子细胞。聚乳酸-聚乙醇酸具有良好的细胞相容性，可作为骨髓基质细胞的载体应用于组织工程的实验。     

聚乳酸-聚羟乙酸/磷酸三钙薄膜预防屈肌腱粘连的实验

目的:探讨在屈肌腱损伤修复后应用和不应用聚乳酸-聚羟乙酸/磷酸三钙薄膜包裹两种情况下,术后不同时期屈肌腱的粘连情况和聚乳酸-聚羟乙酸/磷酸三钙薄膜在肌腱愈合过程中的作用。方法:实验于2004-03/10在东南大学修复重建外科研究所实验室进行。选取健康成熟的三黄鸡40只,以右足第2,3趾深屈肌腱横断后修复作为肌腱粘连的动物模型,取右足第2趾为实验趾、第3趾为对照趾。聚乳酸-聚羟乙酸/磷酸三钙薄膜包裹,术后3,4,8周分别取材。通过生物力学、大体观察、组织学及扫描电镜检查,观测肌腱愈合情况、与周围组织的粘连情况、屈趾功能及假鞘结构。结果:进入结果分析的实验鸡39只。①实验趾肌腱的屈趾功能明显优于对照趾[术后3周:(10.53±1.07),(7.78±0.37)mm,术后4周:(14.96±1.51),(9.37±1.35)mm,术后8周:(19.93±0.81),(11.47±0.15)mm,P<0.05]。②大体观察实验趾在各时间段肌腱与腱周组织的粘连均较对照趾轻,肌腱为内源性愈合,并形成具有正常滑膜A、B型细胞的假鞘结构,与肌腱间有间隙。结论:聚乳酸-聚羟乙酸/磷酸三钙薄膜通过刺激周围组织形成假鞘,阻止来自腱周的粘连,且不影响肌腱正常愈合,是较理想的预防肌腱粘连材料。     

Biocompatibility and biodistribution of suberoylanilide hydroxamic acid loaded poly (DL-lactide-co-glycolide) nanoparticles for targeted drug delivery in cancer

The biodegradable polymeric nanoparticles have been potentially used to carry various chemotherapy agents into cancer cells for targeted drug delivery. Conversely, the biodistribution and toxic effects of these drug-loaded nanoparticles have raised some concerns. In the present study, we tried to explore the prospective histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) loaded poly (DL-lactide-co-glycolide) (PLGA) nanoparticles biocompatibility and biodistribution in animal system. The biocompatibility of SAHA loaded PLGA nanoparticles were evaluated through hemolysis, biochemical and histopathological analysis. The analysis results showed SAHA loaded PLGA nanoparticles has good hemocompatibility, not at all an elevation of blood biochemical parameters and no specific remarkable tissues changes in liver, kidney, lung, and heart as compared with control. The orally administered SAHA loaded PLGA nanoparticles distributions in various organs were confirmed using spectrofluorometry and fluorescence microscope. The results shows nanoparticles were remained detectable in the liver, kidney, heart and lung tissues after 3 days. Moreover, the SAHA loaded PLGA nanoparticles are actively taken up in the A549 lung cancer cells. The overall results conclude that the histone deacetylase inhibitor SAHA loaded PLGA nanoparticles is biocompatible and actively distributed various organs in the animal system. The biocompatible SAHA loaded PLGA nanoparticles may be a suitable anticancer agent in the near feature.     

Crystallization,thermal and mechanical properties of stereocomplexed poly(lactide) with flexible PLLA/PCL multiblock copolymer

In this work, the synthesized PLLA/PCL multi-block copolymers with different compositions were introduced into a stereocomplexed poly(lactide) (sc-PLA) matrix to accelerate the stereocomplexation of PLA enantiomers and improve its inherent brittleness. The PLLA/PCL multi-block copolymers were in different compositions to adjust the molecular weight of the PLLA block. The structure, molecular weight, crystallization behavior, crystal structure and thermal stability of PLLA/PCL multi-block copolymers were investigated. The results indicated that PLLA/PCL multi-block copolymers with controllable structure and composition were successfully synthesized. On this basis, the blends of sc-PLA and PLLA/PCL multi-block copolymers were prepared by solution casting, and characterized. The results revealed that the introduction of PLLA/PCL multi-block copolymers promoted the stereocomplexation of the PLA enantiomers during the melting crystallization process to obtain a complete stereocomplexed material. But the presence of the PCL block leads to a decrease in the melting temperature of the stereocomplex and difficulty in homogeneous nucleation. Compared with sc-PLA, the elongation at break of the blends was significantly improved and their tensile strengths were only slightly reduced. And the thermal stability and mechanical properties of the blends could be adjusted by controlling the content and composition of PCL/PLLA multi-block copolymers. These results revealed that the degree of stereocomplexation and toughness of sc-PLA were improved, which may expand the application fields of PLA-based materials.

The PLLA/PCL multi-block copolymer was introduced into the stereocomplexed PLA matrix, and its effect on the crystallization, thermal and mechanical properties of the stereocomplexed PLA was discussed.     

新型支架材料羟基丁酸与羟基辛酸共聚体的生物相容性

文章选用细胞毒性实验、急性全身毒性实验、溶血实验、热源实验、皮内刺激实验、遗传毒性实验和皮下植入实验等7个生物相容性实验对生物可降解支架材料羟基丁酸与羟基辛酸共聚体的生物相容性进行评价.结果发现羟基丁酸与羟基辛酸共聚体及其浸提液与小鼠成骨细胞共培养时,细胞生长形态均良好,数量逐渐增加,无细胞毒性;羟基丁酸与羟基辛酸共聚体浸提液无急性毒性反应;其溶血率为1.67%,符合ISO规定的溶血率＜5%的标准;将其注入家兔耳缘静脉后未引起发热反应:注入家兔皮内未引起皮肤刺激反应;注入小鼠尾静脉未引起遗传毒性反应:将羟基丁酸与羟基辛酸共聚体膜植入皮下12周,尚未发现明显的炎症反应.提示羟基丁酸与羟基辛酸共聚体具有良好的生物相容性.     

Influence of poly(lactide) stereocomplexes as nucleating agents on the crystallization behavior of poly(lactide)s

The influence of the addition of linear and four-arm poly(lactide) (PLA) stereocomplexes (scPLAs) on the non-isothermal and isothermal crystallization behavior of poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA) from the molten state was investigated. The linear PLAs and four-arm PLA with a similar chain length for each arm were synthesized by ring-opening polymerization. The linear and four-arm scPLAs were then prepared by solution blending and characterized by ¹H-NMR, FTIR, and WAXD analysis. Various mass ratios of the scPLAs were subsequently added to PLLA and PDLA as nucleating agents and specimens were prepared by solution casting. The isothermal and non-isothermal crystallization behavior of the specimens was examined by differential scanning calorimetry and polarized optical microscopy. The SC crystallites effectively promoted the nucleation of the PLAs, thereby increasing the general crystallization rate of the matrix. A 10% content of stereocomplex nucleating agent increased the crystallization rate of PDLA and PLLA by more than 55% and 70%, respectively. Compared with the linear scPLA, the four-arm scPLA more strongly promoted crystallization at higher temperatures. This might be because the greater degree of branching and larger steric hindrance of the four-arm scPLA led to the formation of defective SC crystallites, which was more beneficial for adsorption of the matrix on the crystal surface and permitted the nucleation and growth at higher temperatures. These results demonstrate that scPLAs can potentially be used as nucleating agents to improve the performance and transparency of PLA films.

The influence of the addition of linear and four-arm poly(lactide) stereocomplexes on the crystallization behavior of poly(l-lactide) and poly(d-lactide) from the molten state was investigated.     

乙交酯-丙交酯共聚物与大鼠脊髓组织的生物相容性

观察生物可降解材料乙交酯-丙交酯共聚物支架与大鼠脊髓组织的生物相容性。实验于2005-05/09在首都医科大学附属北京市神经外科研究所损伤修复实验室完成。取健康成年雌性Wistar大鼠8只,体质量250～300g,将组织工程材料乙交酯-丙交酯共聚物移植入大鼠T9水平脊髓半横断损伤处,切除脊髓3mm,乙交酯-丙交酯共聚物支架移植入空隙处,术后每日人工排尿2次,截瘫护理。分别在移植后2,4,8,12周不同时间点电镜下观察支架的降解及组织细胞的生长状况。纳入8只大鼠,均进入结果分析。扫描电镜观察髓内移植后随时间的延长,材料逐步降解,透射电镜观察2周时可见材料表面有纤维细胞、纤维母细胞和巨噬细胞吞噬坏死变性的许旺细胞。4周和8周时可见再生的薄髓纤维,崩解或变性髓鞘,巨噬细胞吞噬坏死变性的许旺细胞较2周时少。12周时材料表面附着再生的有髓神经纤维、纤维细胞和纤维母细胞,巨噬细胞吞噬坏死变性的许旺细胞少见。乙交酯-丙交酯共聚物支架在大鼠脊髓内具有良好的生物相容性。     

Biocompatibility of poly (DL-lactic acid/glycine) copolymers

In this review the authors discuss the polymer chemical, physical and cell biological aspects of poly (DL-lactic acid/glycine) copolymers, both in vitro and in vivo. The mechanism and rate of degradation and the degree of foreign body reaction were evaluated as a function of the molecular composition of the (co)polymer, its initial molecular weight and changes in crystallinity. Data from the literature concerning poly(lactic acid), poly(glycolic acid) and poly(amino acids) are included in this review. The choice to apply the polymers mentioned was determined by their nature: all are present in the human body as natural residues. Upon degradation, biocompatibility will thus not be impaired. The authors conclude that the degradation mechanism of poly(lactic acid), poly(glycolic acid) and poly(amino acids) are similar, i.e. bulk hydrolysis of ester bonds. The initial molecular weight and the chemical composition, determine the rate of degradation and the degree of foreign body reaction.     

Microencapsulation of DNA using poly(DL-lactide-co-glycolide): stability issues and release characteristics.

The design of DNA vaccination delivery systems for the targeting of professional antigen presenting cells could be an interesting approach to elicit cytotoxic T-cell responses to fight viral infections and in cancer therapy. Stability studies with linear high and low molecular DNA and supercoiled plasmid DNA were performed in order to check their ability to withstand stress conditions applied during formulation processes. DNA was tested for integrity by the PicoGreen assay and transfectivity was assessed in cell culture transfection experiments. Double-stranded DNA is extremely stable under physiological conditions in vitro but is rapidly degraded under acidic conditions and high shear forces. Thereby, different stress factors resulted in distinct degradation patterns such as fragmentation and strand separation possibly followed by further decomposition of single-stranded DNA. DNA containing PLGA microparticles as a potential delivery system was prepared by spray-drying. Encapsulation efficiency, DNA stability and burst release varied significantly depending on the different parameters explored in this study. The microencapsulation process was altered to achieve maximal stability of encapsulated DNA by reducing exposure to shear forces and by the addition of NaHCO(3) which acts as a buffering agent and furthermore stabilizes dsDNA against mechanical degradation. Stability of DNA is maintained during the burst release phase, but massive degradation occurred during the second release phase possibly due to acidic catalyzed decomposition. In summary, we feel that microencapsulation of DNA vaccines by spray-drying offers manifold possibilities to design suitable delivery systems in terms of optimizing phagocytosis by APCs and maintaining stability of DNA in phagosomes.