聚乳酸微球对破伤风类毒素疫苗免疫效果的影响

破伤风全程免疫需要连续 3次注射疫苗。为减少注射次数 ,提高接种覆盖率 ,降低辍种率 ,开发具有长效作用的单剂破伤风类毒素控释系统是全球儿童疫苗发展计划的主要目标之一。微球作为疫苗载体是近年来免疫学和疫苗研究领域中的一个热点。本文观察了聚乳酸微球对破伤风类毒素疫苗免疫效果的影响。采用不同分子量的聚乳酸制备不同载药量及粒径的微球 ,分为小粒径微球、大粒径微球、低载药量微球、高载药量微球、空白微球、混合微球 (由小粒径、高载药量及低分子量聚乳酸等剂量比组成 )。将微球混悬于含 0 5 %山梨醇、0 1%羧甲基纤维素及 0 …     

阿霉素磁性壳聚糖微球的制备及释放实验

应用改进的悬浮交联技术制备磁性壳聚糖(chitosan,CS)纳米微球。结果显示:该药物微球基本呈球形,其粒径在200~800 nm之间,并且显示了好的磁响应性。阿霉素(doxorubicin,DOX)为试验药物,DOX和CS以化学键(-N=C-)结合在一起,药物含量在1%~15%(w/w)。pH值的大小对其药物体外释放试验的影响很大,当pH为1、2和4时,7 d内药物的释放从22.0%、13.4%降至4.1%。该微球为pH敏感的磁靶向药物微球。     

缓释抗菌微球复合型组织工程材料水凝胶的制备及性能评价

背景：氧化羟丙基甲基纤维素-透明质酸钠水凝胶体系具有良好的力学性能、生物相容性与降解性,可作为组织工程支架对受损组织起保护支撑作用,也可作为药物载体实现局部缓释作用。目的：制备缓释抗菌微球复合型组织工程材料水凝胶,研究其理化性能、生物学性能、骨诱导性能和抗菌性能。方法：以聚乳酸乙醇酸共聚物、壳聚糖和透明质酸钠为材料,通过乳液法制备出具有多层结构的多孔微球载体,并对酸万古霉素进行负载,制备出抗菌缓释微球;以氧化羟丙基羧甲基纤维素和胺化透明质酸钠为基质制备成可注射水凝胶,并将不同质量浓度的抗菌缓释微球(0.1,0.2,0.3 g/m L)添加到水凝胶中,制备出载抗菌缓释微球的可注射水凝胶,对其理化性能(成胶时间测定、溶胀性能、降解性能)、生物学性能(细胞毒性、细胞溶血性)及成骨性能(碱性磷酸酶活性及诱导成骨基因RUN-x2、骨形态发生蛋白2、骨钙蛋白、Ⅰ型胶原蛋白表达水平)、抗菌性能进行检测及评价。结果与结论：(1)3种载抗菌缓释微球水凝胶具有良好的成胶性能与较小的溶胀比;体外降解扫描电镜结果显示,水凝胶具有稳定的自身降解性能;(2)细胞毒性实验显示,当抗菌缓释微球添加量≤0.2 g/m ...     

聚羟基丁酸-羟基辛酸共聚酯载生长因子的缓释纳米微球

背景:骨形态发生蛋白2可增加软骨细胞和祖细胞基质的产生,可增强组织金属蛋白酶抑制因子1、sox9基因、Ⅱ型胶原以及聚集蛋白聚糖的表达,具有诱导间充质细胞迁徙、增殖、分化,最终促使软骨、骨形成的作用。目的:制备重组人骨形态发生蛋白2聚羟基丁酸-羟基辛酸共聚酯纳米微球系统纳米微球缓释系统,观察微球生长因子形态和粒径分布、载药量、包封率、体外缓释时间及生物活性。方法:采用复乳-干燥法制备重组人骨形成蛋白2聚羟基丁酸-羟基辛酸共聚酯纳米微球系统,体外分离培养猪软骨细胞。实验分为3组:第1组培养液不添加药物做为对照;第2组培养液中添加含20μg/L重组人骨形态发生蛋白2;第3组培养液中添加20μg/L重组人骨形态发生蛋白2聚羟基丁酸-羟基辛酸共聚酯纳米微球系统纳米微球;其中在第2组和第3组又将重组人骨形态发生蛋白2和重组人骨形态发生蛋白2聚羟基丁酸-羟基辛酸共聚酯纳米微球系统纳米微球分别设为55,100μg/L两种的有效浓度,采用MTT法检测微球对软骨细胞增殖的影响,模拟体内条件观察纳米微球的体外缓释性及生物活性。结果与结论:该纳米微球表面光滑圆整,球体大小均匀,粒径为231-415 nm,扫描电镜平均粒径323 nm。微球的包封率和载药量分别为(79.63±0.16)%和(1.92±0.16)%。根据15 d内对重组人骨形态发生蛋白2聚羟基丁酸-羟基辛酸共聚酯纳米微球的体外释药的观察,保持持续释放重组人骨形态发生蛋白2,且释放的浓度呈增长水平。该微球缓释系统有生物活性,能显著促进猪软骨细胞的增殖,其效应高于单纯重组人骨形态发生蛋白2的效应。提示重组人骨形态发生蛋白2聚羟基丁酸-羟基辛酸共聚酯纳米微球缓释系统包封率、载药量、体外释药性以及生物活性符合纳米微球的一般规律,能够满足相应的软骨缺损修复要求。     

两性霉素B缓释微球的制备及缓释性能研究

为了更好地研究药物载体材料对药物微球缓释性能的影响,本研究将可完全生物降解的共聚物作为壁材以相分离法制备含抗真菌药物两性霉素B的微球,研究了不同溶剂/非溶剂、不同分子量共聚物、不同配比共聚物、不同表面活性剂及其不同用量等因素对微球的粒径大小、分布、药物包封率和药物体外释放等性能的影响。使用透射电镜（TEM）和原子力显微镜（AFM）观察微球的表面形貌,使用激光粒度分析仪测试微球的粒径大小及分布,使用紫外分光光度计测定药物的包封率。研究发现,聚合物特性粘度和分子量越大,聚合物中LA：PEG的配比越大,微球粒径越大,分布越宽;微球粒径越大,包封率也较大;AmB/PLA-PEG微球具有缓释性能,且含药微球的释放性能与微球的粒径,包封率等因素有关。     

Fe_3O_4空心磁纳米微球制备工艺条件的影响因素

背景:空心微球材料具有很好的生物相容性,在生物医学和化学等许多领域得到广泛的应用。目的:分析Fe3O4空心磁性纳米微球制备流程中反应温度、反应时间、洗涤次数、超声时间工艺条件对粒径的影响。方法:以聚氧乙烯-聚氧丙烯-聚氧乙烯-嵌段共聚物F127为原料,用共沉淀法制备空心超顺磁性纳米微球。运用正交试验的数学方法设计一个4×3的正交实验模型,从反应温度、反应时间、洗涤次数、超声时间4个方面考察不同制备条件对空心磁性纳米微球粒径大小的影响。结果与结论:得到的最佳实验制备条件:在75℃下,充分反应6h,用甲醇/去离子水反复洗涤3次之后,用功率为30%的超声处理20min。样品通过0.22μm滤嘴过滤后,用粒径分布仪、X射线衍射和透射电子显微镜对产物进行表征观察,证实用最优的实验条件制备的空心Fe3O4磁性纳米微球粒径为37.5nm,外壳厚度10nm左右,颗粒大小均匀,分布较好。     

免疫磁性海藻酸钠载药纳米微球的制备与评价

靶向治疗系统是目前研究的热点,用微乳化-离子交联方法制备包覆阿霉素的碳包铁/海藻酸钠复合纳米微球,以水溶性碳二亚胺为交联剂,将载药微球与单抗Hab18连接,制备出了免疫磁性药物纳米微球.对该免疫磁性微球的理化性能进行了表征,同时检测了免疫磁性微球中抗体的活性和免疫磁性微球与靶细胞的体外结合情况,结果表明,免疫磁性药物纳米微球平均粒径约为171.2nm,外观为球型,铁含量为14.6%,载药量为10.8%,且具有强磁响应性和长时间药物缓释效果.同时在体外该微球能够与靶细胞特异性结合.这种免疫磁性药物纳米微球有望成为一种优良的靶向肿瘤药物载体.     

转化生长因子β3/聚乳酸-羟基乙酸微球对干细胞的调控

文题释义：转化生长因子β3：是转化生长因子β超家族成员,在胚胎软骨形成的多个时期都是必不可少的软骨组织形成的关键调节因子,可以促进间充质干细胞迁移并诱导其向软骨组织分化与成熟,促进软骨缺损的愈合。 聚乳酸-羟基乙酸微球：属于食品药品监督管理局(Food and Drug Administration,FDA)批准的可生物降解聚合物,具有可控的降解性和良好的生物相容性,被广泛应用于医药领域。由于其生物可降解性,聚乳酸-羟基乙酸微球微球被广泛应用于小分子药物、蛋白质和其他大分子药物的可控持续释放。 背景：转化生长因子β3/聚乳酸-羟基乙酸缓释微球系统可使药物在作用部位维持有效药物浓度,提高生长因子的利用率。 目的：优化转化生长因子β3/聚乳酸-羟基乙酸缓释微球制备工艺,探究其对脂肪间充质干细胞增殖和迁移的影响。 方法：采用乳化-溶剂挥发法制备转化生长因子β3/聚乳酸-羟基乙酸缓释微球,并对微球的形态、粒径大小、药物空间分布、包封率、载药量和缓释性能进行表征。将转化生长因子β3/聚乳酸-羟基乙酸缓释微球溶解于PBS中,于相应的时间点检测上清液中转化生长因子β3浓度,对应时间点扫描电镜观察微球形态。将脂肪间充质干细胞分6组培养,分别加入培养基(阴性对照)、含转化生长因子β3的培养基、含空白聚乳酸-羟基乙酸微球的培养基、含10,100,1 000 g/L转化生长因子β3/聚乳酸-羟基乙酸微球的培养基,于对应的时间点CCK-8法检测增殖。将脂肪间充质干细胞分别与培养基(阴性对照)、含转化生长因子β3的培养基、含聚乳酸-羟基乙酸微球的培养基、含10,100,1 000 g/L转化生长因子β3/聚乳酸-羟基乙酸微球的培养基以非接触方式共培养24 h,检测细胞迁移数量。结果与结论：①转化生长因子β3/聚乳酸-羟基乙酸微球呈球形,表面光滑,无粘连,粒径均匀分布,微球直径2-50 μm,微球内的蛋白药物分布均匀,具有较高的包封率与载药量;②缓释微球具有良好的降解性能,体外可于6个月后完全降解;同时具有良好的缓释性能,体外可缓慢释放转化生长因子β3长达45 d;③空白微球及含转化生长因子β3的缓释微球对脂肪间充质干细胞增殖无影响;④空白微球对脂肪间充质干细胞的迁移无影响,转化生长因子β3及含转化生长因子β3的缓释微球可促进脂肪间充质干细胞的迁移,不同质量浓度缓释微球间的促进效果无差异;⑤结果表明,转化生长因子β3/聚乳酸-羟基乙酸缓释微球可在不影响脂肪间充质干细胞增殖的情况下促进其迁移。 ORCID: 0000-0002-2267-4589(杨振) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

乳酸—乙醇酸共聚物（8：2）微球在大鼠体内的降解

制备了乳酸—乙醇酸(8:2)共聚物的空白微球,经过筛、~(60)Co灭菌后,注射于大鼠后腿肌肉中。微球直径65-80μm。每隔一定时间处死大鼠,并从注射部位分离得到微球。微球用电镜观察并用GPC测定其分子量。结果表明,此聚合物微球在大鼠体内完全降解约需6个月且分子量的下降与扫描电镜照片显示的微球形态的变化相符合。     

用溶解蒸发方法制备的聚(D.L丙交酯/乙交酯)型微球的体内外降解

用溶解蒸发制备各种聚(α-羟基酸)微球,研究γ消毒对微球稳定的影响,并证实体内外的降解过程.经γ-射线消毒后明显地降低了该聚合物的分子量,并且这种降解继续存在,γ-射线改变了顺铂微球的控制释放方式.用微球使大鼠肝栓塞后,进行炎症反应的组织学研究,同时对降解聚合物进行凝胶渗透层析分析,聚合物的降解率随乳酸链中乙醇单位含量而增加.作者研究了顺铂填充的各种类型微球结构特点及释放动力学.它们是由不同分子量的D,L乳酸与乙醇酸共聚物和立体共聚物制备的.这些微球含有50%以上顺铂,根据顺铂结晶的分布和制备过程,得到了各种类型的顺铂微球.作者的目的是研究不同行为对微球降解的影响,如γ-射线,体内外降解.用大鼠肝栓塞来进行体内研究,观察其生物相容性,确     

Design and release kinetic pattern evaluation of indomethacin microspheres intended for oral administration

Indomethacin has been incorporated into either ethylcellulose (EC) or Eudragit RL microspheres by a solvent-evaporation process. Production variables have been tested in an attempt to produce indomethacin microspheres having adequate oral controlled-release properties. In spite of high drug content in the ethylcellulose microspheres, the indomethacin release rate was too slow and incomplete. Although the addition of an hydrophilic polymer, polyethylene glycol), to the EC polymer enhanced the indomethacin release rate, it was not possible to reach release profiles suitable for oral use. Therefore, indomethacin was incorporated into a more permeable polymer, Eudragit RL. While incorporation efficiency decreased with increasing initial concentration of indomethacin, adequate oral-release profiles were achieved. It was found that all the global-release profiles yielded by the indomethacin-loaded Eudragit RL microspheres conformed to the Higuchi diffusional model of dispersed drug particles in spherical micromatrices and not to the desorption kinetic model of a dissolved drug from a monolithic spherical device.     

Electrospraying: a facile technique for synthesis of chitosan-based micro/nanospheres for drug delivery applications

Electrospraying is a novel technique for the generation of micro/nanospheres for biomedical applications. Apart from being a high yield technique; electrospraying has an added advantage of not making use of an external dispersion/emulsion phase which often involves ingredients that are undesirable for biomedical applications. In this study, we report the use of electrospraying for the synthesis of chitosan micro/nanospheres. The focus was to optimize the fabrication parameters involved in electrospraying for reproducible synthesis of chitosan based micro/nanospheres and to study their potential as delivery vehicles for bioactive agents. The influence of the following was studied (i) electrospraying voltage, (ii) needle gauge, (iii) concentration of chitosan solution, (iv) concentration of acetic acid solution, and (v) electrospraying distance. SEM analysis demonstrated that microspheres of less than 1 mum were obtained when chitosan concentration was 2% dissolved in 90% acetic acid. The working distance and needle gauge that yielded favorable results were 7 cm and 26 g, respectively. Average particle size of ampicillin loaded chitosan micro/nanospheres was 520 nm with zeta potential of +28.2 mV and encapsulation efficiency of 80.4%. The particles were characterized for drug release kinetics and results demonstrated an initial burst release followed by a sustained release over a period of 120 h. Further, antibacterial activity of drug loaded micro/nanospheres demonstrated that the encapsulated drug was in its active form postexposure to high voltage during electrospraying. This study indicates that electrospraying is a facile technique for the synthesis of chitosan micro/nanospheres for drug delivery applications.     

Strategies for the nanoencapsulation of hydrophilic molecules in polymer-based nanoparticles

Hydrophilic drug delivery still remains a challenge; this either being attributed to the fragility and poor cellular penetration of macromolecules, or to the unsuitable pharmacokinetics and toxicity of small drugs, for instance anticancer agents. By offering more favourable pharmacokinetics and protection of the drug, encapsulation in polymer nanoparticles constitutes an attractive possibility to overcome these problems. This review provides an overview of the strategies that have been developed for encapsulating hydrophilic molecules in polymer-containing nanoparticles, e.g. nanospheres and nanocapsules. Polymer nanospheres are loaded either by drug entrapment (by pH modification, use of reverse micelles or the addition of a polyanion) and generally produce a poor level of entrapment efficiency, or molecule sorption onto the nanosphere surface (by pH modification, use of high drug concentration, or ion-pair formation) with the drawbacks of a less-well protected drug from degradation and a faster drug release. Another strategy consists of the use of aqueous-core nanocapsules, generally surrounded by a thin polymer layer, in which hydrophilic molecules are directly solubilised in internal water, and are thus entrapped within the nanocapsule core, assuring drug protection and sustained release. Nanocapsules require less polymer compared to nanospheres; on the other hand, when the drug is entrapped, it has to be added before or during the formulation process, and is thus likely to be degraded. Overall, drug encapsulation in polymer nanoparticles provides a better pharmacokinetic profile and bioavailability, enhanced anticancer activity, reduced drug toxicity and modified drug distribution as compared to free drugs.     

Preparation of floating alginate gel beads for drug delivery to the gastric mucosa

Alginate gel beads containing ethylcellulose (ALECs) were prepared and investigated with regard to buoyancy, in vitro and in vivo drug release profiles, and drug targeting specificity in the gastric mucosa. When the ethylcellulose (EC) content of ALECs containing metronidazole (MZ) was higher than 3%, the beads floated in all test solutions with a specific gravity of approx. 1.01. ALECs containing 5% EC released MZ gradually and floated throughout the experimental period in simulated gastric juice (pH 1.2), and all of the drug had been released after 90 min. When we orally administered ALECs to guinea pigs, about 85% of the incorporated MZ was released at 1 h. The MZ concentration of the gastric mucosa after administration of ALECs was greater than that observed with administration of MZ solution, despite lower serum concentrations. Furthermore, the similar data were obtained for ALECs with 7% EC. These results suggest that ALECs may become a practical vehicle for delivering drugs to the gastric mucosa.     

硫酸庆大霉素-壳聚糖纳米粒的制备及性能评价

背景：庆大霉素珠链是较早用于治疗慢性骨髓炎的局部释药系统,但是由于其不能在体内降解吸收,须二次取出,因而限制了其的应用。因此国内外学者一直致力于可吸收材料负载抗生素装置的研究。 目的：制备负载庆大霉素的壳聚糖纳米粒,评价其性能,观察其体外释药行为及体外抗金黄色葡萄球菌的作用。 方法：以壳聚糖为药用载体,硫酸庆大霉素为模型药物,三聚磷酸钠为离子交联剂,采用离子交联法制备庆大霉素-壳聚糖纳米粒,在MH平板上进行抑菌实验,观察及评价其抑制金黄色葡萄球菌的作用。 结果与结论：制备的纳米粒形态为类圆形,粒径为40~70 nm,包封率及载药量分别为31.3%和15.4%,体外释药可持续14 d左右,对金黄色葡萄球菌的体外抑菌效果可持续25 d,在第5天纳米粒的抑菌作用达到最大,随着时间的推移,抑菌圈逐渐缩小。     

重组人骨形态发生蛋白2壳聚糖纳米微球的制备及体外细胞毒性

背景：通过各种微球负载骨生长因子使骨形态发生蛋白达到缓释效果逐渐成为研究热点,但关于载药壳聚糖纳米微球的生物相容性特别是细胞毒性的报道较少。 目的：对重组人骨形态发生蛋白2壳聚糖纳米微球进行细胞毒性检测,评估应用壳聚糖纳米微球作为重组人骨形态发生蛋白2缓释载体的生物安全性。 方法：通过离子交联法制备空白壳聚糖纳米微球,应用透视电镜观察微球的形态,激光粒径分析其粒径分布;通过重组人骨形态发生蛋白2壳聚糖纳米微球体外细胞毒性试验评估微球的生物安全性。 结果与结论：离子交联法制备的壳聚糖微球,球形规整,分散均匀,微球平均粒径为230 nm,分布较集中。载药及空白微球的反应分级为0或1级,均为合格。提示,离子交联法制备可成功制备出负载重组人骨形态发生蛋2的纳米微球,且微球细胞毒性检测合格,为进一步的骨组织工程研究提供理论实验基础。     

Cellular evaluation of oral chemotherapy carriers

Hydrogel nanospheres composed of methacrylic acid and poly(ethylene glycol) were loaded with bleomycin and tested as a potential oral delivery system for chemotherapeutic agents. The gastrointestinal epithelium was modeled through the use of Caco-2 monolayers for studies of permeation enhancement by the carriers as well as bleomycin transport. Bleomycin efficacy following release from the carrier was evaluated with a DLD-1 tumor cell model. The nanospheres release bleomycin in response to a pH increase similar to that seen when passing from the stomach into the upper small intestine. These carriers can also increase the permeability of a model of the epithelial barrier, which would hopefully improve drug transport into the bloodstream. Efficacy studies using a tumor cell model showed retention of activity for bleomycin following loading and release from the nanospheres. The carriers described performed well during in vitro evaluation and can hopefully expand the spectrum of chemotherapeutic agents capable of being administered orally.     

Calcium phosphate/chitosan composite scaffolds for controlled in vitro antibiotic drug release

Macroporous chitosan scaffolds reinforced by beta-tricalcium phosphate (beta-TCP) and calcium phosphate invert glasses were fabricated using a thermally induced phase separation technique. These porous composite materials were specially designed as both a drug carrier for controlled drug release and a scaffold for bone regeneration. The controlled drug release of antibiotic gentamicin-sulfate (GS) loaded scaffolds and morphology of osteosarcoma MG63 cells cultured on the scaffolds were studied. In comparison with the GS loaded pure chitosan scaffolds, the initial burst release of GS was decreased through incorporating calcium phosphate crystals and glasses into the scaffolds, and the sustained release for more than 3 weeks was achieved. The possible mechanisms for the controlled drug release were investigated by SEM, FTIR, and measurements of the pH values of the PBS solution during the drug release test. SEM micrographs showed no apparent morphological differences for osteoblastic cells grown on the pure chitosan scaffolds and those grown on composite scaffolds. The cells were attached and migrated on these scaffolds, and exhibited a biological appearance, suggesting a good cellular compatibility.     

Redox/pH dual stimuli-responsive biodegradable nanohydrogels with varying responses to dithiothreitol and glutathione for controlled drug release

A new type of redox/pH dual stimuli-responsive poly(methacrylic acid) (PMAA)-based nanohydrogels was prepared from methacrylic acid and N,N-bis(acryloyl)cystamine crosslinker via distillation-precipitation polymerization. The nanohydrogels could be easily degraded into individual linear short chains (M(n) ≈ 1200, M(w)/M(n) < 1.1) in the presence of 10 mM dithiothreitol (DTT) or glutathione (GSH). Doxorubicin (DOX) as a model anti-cancer drug was high efficiently loaded into the nanohydrogels (up to 42.3 wt%) due to the strong electrostatic interactions between the amine group in doxorubicin (DOX) and the carboxyl groups in the nanohydrogels at a physiological pH. The cumulative release profile of the DOX-loaded nanohydrogels showed a low level of drug release (less than 15 wt% in 24 h) at pH 7.4, and was significantly accelerated at a lower pH (5.0) and reducing environment (over 91 wt% in 5 h), exhibiting an obvious pH/redox dual-responsive controlled drug release capability. The drug release behavior of the DOX-loaded nanohydrogels in the presence of GSH was very different from the DTT as the loaded DOX could be quickly released in the presence of GSH, but not in DTT. The possible reason is the synergic effect of reduction and charge exchange of GSH at a low pH. The dose-dependent cytotoxicity of the DOX-loaded nanohydrogels was studied by the CCK-8 assay; the DOX-loaded nanohydrogels could be taken up quickly by human glioma (U251MG cells) via endocytosis, and then biodegraded to release the loaded drugs, which exhibited a comparably anti-tumor efficacy. These nanohydrogels possess many favorable traits, such as excellent biocompatibility and biodegradability, adequate drug loading capacity, minimal drug release under an extracellular condition (non-reductive), and rapid drug release in response to the intracellular level of pH and reducing potential, which endow them as a promise candidate for delivering anti-cancer drugs.     

Protein encapsulation within poly(ethylene glycol)-coated nanospheres. II. Controlled release properties.

The development of injectable nanoparticulate "stealth" carriers for protein delivery is a major challenge. The aim of this work was to investigate the possibility of achieving the controlled release of a model protein, human serum albumin (HSA), from poly(ethylene glycol) (PEG)-coated biodegradable nanospheres (mean diameter of about 200 nm) prepared from amphiphilic diblock PEG-poly(lactic acid) (PLA) copolymers. HSA was efficiently incorporated into the nanospheres, reaching loadings as high as 9% (w/w). Results of the in vitro release studies showed that it is possible to control the HSA release by choosing the appropriate nanosphere size, loading, and composition. These results also revealed that, following their release, HSA molecules readsorbed onto the nanospheres surfaces when they were not protected by a PEG coating. We were surprised to observe that in spite of the water uptake of the PLA-PEG nanospheres [11-29% (w/w)], the copolymer did not significantly degrade after a 15-day incubation period. Therefore, we concluded that during this time HSA release from PLA-PEG nanospheres followed a diffusion mechanism where bulk erosion and surface desorption were negligible.