氢氧化镁调控BSA-PLGA微球体外释放的研究

目的:探索氢氧化镁对BSA微球体外释放的影响,优化BSA微球的制备工艺。方法:通过水包油包固复乳法制备BSA-PLGA微球。先将BSA与葡聚糖制备成玻璃体颗粒,再将玻璃体颗粒与氢氧化镁包裹进PLGA中,制备成缓释微球。在扫描电镜下观察其形态。然后用Micro BCA法测定其包封率和载药量,并考察其体外释放行为。结果:所制得的微球粒径约60μm,呈较好的球形。添加氢氧化镁后,BSA微球的包封率和载药量都有显著提高。不同含量的氢氧化镁对BSA微球的包封率和载药量影响也不同。在体外释放过程中,载有氢氧化镁的微球14天累积释放量为(85.10±2.67)%,而对照组不到80%。结论:通过调整氢氧化镁的量,可以制得形态完整,大小均匀,突释较小的BSA微球。     

rhEGF缓释微球对糖尿病皮肤溃疡创面修复的 作用

采用W/O/W方法制备聚乳酸-羟基乙酸共聚物(PLGA)载重组人表皮生长因子(rhEGF)缓释微球, 表征了缓释微球形貌和粒径分布, 研究了体外释放行为, 进行了细胞实验和动物实验. 结果显示：微球形貌规则, 粒径均匀; 药物包封率达85.6%; 缓释时间达24 h. 细胞实验表明, 微球比rhEGF原液具有更好的促进细胞增殖作用; 通过观察动物实验中溃疡面积变化、组织病理切片和PCNA表达, 发现微球组治疗效果优于生长因子原液组和空白对照组, 并且具有显著性差异. 本研究为rhEGF缓释微球技术的临床应用提供了重要的科学依据.     

包封不对称膜高分子囊泡对PLGA微球中蛋白释放行为的改善作用

目的:研究含蛋白的不对称膜高分子囊泡包封进PLGA微球后对其体外释放动力学的改善作用.方法:将包封有BSA蛋白的不对称膜高分子囊泡采用S/O/W法包裹进PLGA微球中,制备复合微球,对微球表征后,以包封葡聚糖颗粒的微球做对照品,于37℃测定微球的体外释放,比较两者的释放曲线,考察不对称膜高分子囊泡时微球中蛋白释放的改善作用.结果:①经扫描电镜(SEM)观察,包裹高分子囊泡的复合微球形态圆整,表面光滑,平均粒径为75.20μm,粒径较为均匀,复合微球制备成功.②比较复合微球和对照微球的释放曲线,发现对照微球有较小的突释,而复合微球的几乎没有突释效应.结论:不对称膜高分子囊泡包封进PLGA微球后可以很好的改善蛋白的释放行为,获得更为理想的释放曲线.     

壳聚糖-海藻酸钠包裹Hp全菌蛋白微球剂的研制及其表征分析

以壳聚糖、海藻酸钠为主要合成材料包裹幽门螺杆菌全菌超声蛋白抗原 ,制备新型Hp疫苗制剂。采用一定工艺 ,将海藻酸钠、壳聚糖以及Hp超声全菌抗原制备成W /O/W微球。通过扫描电镜、粒径分布仪等设备检测微球粒径大小 ;微球溶出度仪、Lowry法检测蛋白含量、高压液相色谱等检测微球的蛋白的包封率以及释放速率 ;12 5I标记后口服观测微球的定向靶向作用等。所制备微球形态规则 ,粒径均在 10 μm以内 ;包封率达到 4 1%左右 ;整个包封过程对蛋白没有任何降解作用 ;微球呈缓 快 缓释药模式 ,药物缓释时间可长达 72h ;微球在肠PP结分布明显高…     

载阿霉素PLGA纳米微球的制备及性质研究

目的:制备新型癌症化疗制剂载阿霉素(Adriamycin)、聚乳酸-羟基乙酸共聚物(PLGA)纳米微球(ADM-PLGA-NP),研究其性质及体外释药特点。方法:以聚乳酸-羟基乙酸共聚物为包封材料,阿霉素为模型药物,采用复乳蒸发法制备ADM-PLGA-NP,扫描电镜观察微球形态,激光粒度分析仪检测粒径分布,紫外分光光度法计算载药率及包封率,体外药物释放实验考察微球对ADM的缓释作用。结果:ADM-PLGA-NP外观呈球形,平均粒径约(237±12.7)nm,载药量及包封率分别为(6.42±1.67)%和(53.82±8.34)%,药物在体外缓慢释放,5 d累积释放量达85%。结论:通过复乳蒸发法制备的ADM-PLGA-NP性质稳定,具有药物缓释性,有望成为一种新型的药物化疗载体。     

干扰素α缓释微球的制备及体外释放研究

目的:开发一种有效地长效缓释干扰素α微球制剂。方法:利用S/O/W乳剂-挥发法制备了包裹干扰素α多糖颗粒的PLAG微球,对其外观形态进行了考察,并用ELISA方法考察了微球体外释放效果。结果:制备的干扰素α微球圆整光滑,粒径均匀;经24天体外释放,累计释放率达到80%以上。结论:通过包封包裹干扰素α的多糖颗粒进PLGA微球,有效地保护了干扰素α在微球中的活性,实现了长效缓释,是一种可行的缓释方案。     

装载于PLGA中的5-氟尿嘧啶缓释微球的制备及其体外释放的研究

目的:研究装载于不同分子量的PLGA中的5-氟尿嘧啶微球的制备方法及其在体外条件下的缓释行为。方法:以水包油包固复乳法将5-氟尿嘧啶包裹在高分子聚乳酸-聚羟基乙酸共聚物(PLGA)中,形成缓释微球,考察其大小,外观,包封率等理化性质,以紫外分光光度法为检测方法研究其体外释放行为。结果:经扫描电子显微镜观察,所制备的微球形态完整,大小较均匀。具有一定得包封率和载药量,体外释放研究表明其处方1和处方2的缓释时间为8天和23天。结论:以水包油包固复乳法制备的PLGA 5-氟尿嘧啶微球能够达到缓释的目的。     

装载于PLGA中的5-氟尿嘧啶缓释微球的制备及其体外释放的研究

目的：研究装载于不同分子量的PLGA中的5-氟尿嘧啶微球的制备方法及其在体外条件下的缓释行为。方法：以水包油包固复乳法将5-氟尿嘧啶包裹在高分子聚乳酸-聚羟基乙酸共聚物（PLGA）中,形成缓释微球,考察其大小,外观,包封率等理化性质,以紫外分光光度法为检测方法研究其体外释放行为。结果：经扫描电子显微镜观察,所制备的微球形态完整,大小较均匀。具有一定得包封率和载药量,体外释放研究表明其处方1和处方2的缓释时间为8天和23天。结论：以水包油包固复乳法制备的PLGA 5-氟尿嘧啶微球能够达到缓释的目的。     

PLGA微球复合明胶组织工程支架缓释蛋白药物的研究

目的：研究PLGA微球复合明胶支架对蛋白药物的释放影响。方法：将模型蛋白BSA通过复乳法制备成缓释PLGA微球,然后将微球埋置于明胶支架中,形成担载蛋白的PLGA微球复合明胶组织工程支架。考察复合支架体外蛋白释放行为,并用MicroBCA法定量测定释放的BSA量,采用β-半乳糖苷酶催化ONPG的方法检测制备前后蛋白的活性,并与不含PLGA微球直接担载蛋白的支架做对照。结果：PLGA微球复合支架蛋白的包封率能达到73．2％,其中第一天释放20％,对蛋白活性的保持达到70％以上。结论：微球复合明胶支架可以改善一般组织工程支架蛋白药物的突释,提高蛋白药物在制剂,贮存,释放过程中的稳定性。     

姜黄素壳聚糖微球的制备及其在体内外释放度的研究

目的:研究响应面法优化姜黄素壳聚糖微球制备的工艺参数,提高姜黄素的溶出度.方法:采用离子交联法制备姜黄素缓释微球,以微球的载药量和包封率为考察指标,采用星点设计考察配制壳聚糖的醋酸浓度、药物载体的比例以及交联剂浓度对微球制备工艺的影响,对结果进行二次多项式拟合,并根据最佳数学模型进行预测.结果:姜黄素壳聚糖微球最优制备工艺参数为:醋酸的浓度为1％,载体药物比例为0.83,交联剂的浓度为0.15％,载药量和包封率的预测值和理论值偏差分别为0.47％和3.2％.结论:响应面法优化姜黄素壳聚糖微球制剂处方具有很好的预测性,体内外药物释放度研究表明,最优条件下制备的微球可以在提高姜黄素溶出度的前提下缓慢释放达12h.     

重组人粒细胞集落刺激因子缓释微球的研究

目的：研究固体／油／水法制备重组人粒细胞集落刺激因子缓释微球,为开发其缓释剂型进行初步研究。方法：以聚乳酸．聚羟乙酸共聚物（PLGA）为载体材料：用固体／油／水法和水／油／水法制备载rhG-CSF缓释微球;考察粒径大小、外观、包封率等理化性质;用MieroBCA法考察微球的体外释药特性及影响因素;用SEC-HPLC和MTT比色法初步评价了微球制备工艺过程对rhG-CSF稳定性的影响。结果：两种方法制得的微球形态圆整、分散性良好,包封率均超过80％。固／油／水法制得的微球体外释放在2周内可超过90％,而水／油／水法制得的微球在相同的时间内仅释放30％。对于固／油／水法制备过程,SEC-HPLC法测定蛋白无明显聚集体出现,MTT法测定蛋白活性无明显损失。结论：实验证明了固／油／水法制备的PLGA微球可以实现2周以上的体外缓释。     

左旋多巴甲酯缓释微球的研究

目的：由于长期服用左旋多巴治疗帕金森病,其药物浓度波动刺激易引起异动症,本实验旨在制备突释小,药物释放浓度稳定的左旋多巴甲酯微球制剂。方法：将左旋多巴甲酯用复乳法包裹于PLGA微球内,采用C18反相色谱研究药物包封率和体外释放行为。结果：通过调节药物浓度和不同高分子组合筛选出突释小,包封率高且缓慢释放的处方。结论：左旋多巴甲酯包裹于PLGA能实现理想的缓释效果,降低药物浓度波动,为后期药效学实验提供基础。     

Preparation and quality by design assisted (Qb-d) optimization of bioceramic loaded microspheres for periodontal delivery of doxycycline hyclate

PLGA (Lactic- co-glycolic acid) coated chitosan microspheres loaded with hydroxyapatite and doxycycline hyclate complex were developed in the present study for periodontal delivery. A modified single emulsion method was adopted for the development of microspheres. Formulation was optimized on the basis of particle size, drug loading and encapsulation efficiency with the central composite design using 2³ factorial design. Microspheres were optimized and electron microscopy revealed their spherical shape and porous nature. In-vitro study showed initial burst and then sustained release behavior of the formulation for 14 days. Further, in-vitro antibacterial study performed on E. coli (ATCC-25922) and S. aureus (ATCC-29213) revealed concentration dependent activity. Also, in-vitro cyto-toxicity assessment ensures biocompatibility of the formulation with the fibroblast’s cells. Overall, the quality by design assisted PLGA microspheres, demonstrated the desired attributes and were found suitable for periodontal drug delivery.     

血管内皮生长因子(VEGF)乳液法电纺纤维膜的体外研究

目的:研究担载血管内皮生长因子(VEGF)的乳液法电纺纤维膜的亲水性能、外观形态和机械性能,纤维膜中VEGF的包封率和体外释放动力学,为评价其能否应用于血管再生领域的研究奠定基础。方法:将VEGF水溶液通过W/O乳液法制备成缓释VEGF的生物可降解的丙交酯-乙交酯共聚物(PLGA)静电纺丝纤维膜,对该纤维膜的接触角、外观形态、机械性能进行表征,Elisa法测定该纤维膜的体外14天的释放行为,分别观察纤维膜释放0天、7天、14天后的电镜图。结果:加入VEGF后,纤维膜的接触角由140.0°减小到136.1°,亲水性增强,具有类似细胞外基质(ECMs)网状结构和良好的力学性能,纤维膜第1天的突释不超过载药量的50%,电镜图下显示纤维膜释放1周时纤维发生断裂。结论:通过乳液法制备的担载VEGF的电纺纤维膜具有良好的物理性能,能够持续缓释VEGF,可作为血管再生的组织工程支架进行深入研究。     

Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate

This study was conducted to develop formulations of hydrocortisone butyrate (HB)-loaded poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NP) suspended in thermosensitive gel to improve ocular bioavailability of HB for the treatment of bacterial corneal keratitis. PLGA NP with different surfactants such as polyvinyl alcohol (PVA), pluronic F-108, and chitosan were prepared using oil-in-water (O/W) emulsion evaporation technique. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential, and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when nanoparticles were suspended in thermosensitive gels and zero-order release kinetics was observed. In HCEC cell line, chitosan-emulsified NP showed the highest cellular uptake efficiency over PVA- and pluronic-emulsified NP (59.09?±?6.21%, 55.74?±?6.26%, and 62.54?±?3.30%, respectively) after 4 h. However, chitosan-emulsified NP indicated significant cytotoxicity of 200 and 500 μg/mL after 48 h, while PVA- and pluronic-emulsified NP exhibited no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases.     

乳液法静电纺丝PLGA组织工程缓释纤维的研究

目的：研究Dextran对蛋白药物的释放影响。方法：将模型蛋白BSA溶解于多糖溶液中,通过W/O乳液法静电纺丝制备缓释纤维。采用MicroBCA法测定该纤维体外释放行为,采用SEC-HPLC检测制备前后蛋白的聚集程度,并与不含多糖的BSA纤维做对照。结果：添加Dextran以后蛋白的包封率由52.68%提高到63.92%,第一天突释不大于药物载量的15%,对蛋白单体的保持达到85%以上。结论：Dextran可以改善一般组织工程纤维中蛋白药物的释放,提高蛋白药物在制剂、贮存、释放过程中的稳定性,增加纤维的载药量。     

Polyelectrolyte nanoparticles based on water-soluble chitosan-poly(l-aspartic acid)-polyethylene glycol for controlled protein release

Water-soluble chitosan (WSC)-poly(l-aspartic acid) (PASP)-polyethylene glycol (PEG) nanoparticles (CPP nanoparticles) were prepared spontaneously under quite mild conditions by polyelectrolyte complexation. These nanoparticles were well dispersed and stable in aqueous solution, and their physicochemical properties were characterized by turbidity, FTIR spectroscopy, dynamic light scattering (DLS), transmission electron microscope (TEM), and zeta potential. PEG was chosen to modify WSC-PASP nanoparticles to make a protein-protective agent. Investigation on the encapsulation efficiency and loading capacity of the bovine serum albumin (BSA)-loaded CPP nanoparticles was also conducted. Encapsulation efficiency was obviously decreased with the increase of initial BSA concentration. Furthermore, its in vitro release characteristics were evaluated at pH 1.2, 2.5, and 7.4. In vitro release showed that these nanoparticles provided an initial burst release, followed by a slowly sustained release for more than 24 h. The BSA released from CPP nanoparticles showed no significant conformational change compared with native BSA, which is superior to the BSA released from nanoparticles without PEG. A cell viability study suggested that the nanoparticles had good biocompatibility. This nanoparticle system was considered promising as an advanced drug delivery system for the peptide and protein drug delivery.     

Design of Methylprednisolone Biodegradable Microspheres Intended for Intra-articular Administration

This study aimed to design methyprednisolone (MP)-loaded poly(d,l lactide-co-glycolide) (PLGA) microspheres (MS) intended for intra-articular administration. MP was encapsulated in four different types of PLGA by using an S/O/W technique. The effects of β-irradiation at the dose of 25 kGy were evaluated on the chemical and physicochemical properties of MS and the drug release profiles. The S/O/W technique with hydroxypropylmethylcellulose (HPMC) as surfactant allowed obtaining MS in the tolerability size (7–50 μm) for intra-articular administration. The MP encapsulation efficiency ranged 56–60%. HPMC traces were evidenced in the loaded and placebo MS by attenuated total reflectance Fourier transform infrared spectroscopy. MS made of the capped PLGA DL5050 2M (MS 2M) and uncapped PLGA DL5050 3A (MS 3A) prolonged the release of MP over a 2- to 3-month period with a triphasic (burst release–dormant period–second release pulse) and biphasic release pattern, respectively. The β-irradiation did not significantly alter the morphology, chemical, and physicochemical properties of MS. The only variation was evidenced in the drug release for MS 2M in term of shorting of the dormant period. The minimal variations in the properties of irradiated PLGA MS, which are in disagreement with literature data, may be attributed to a radioprotecting effect exerted by HPMC.     

Preparation and optimization of rivastigmine-loaded tocopherol succinate-based solid lipid nanoparticles

Rivastigmine hydrogen tartrate (RHT) is a pseudo-irreversible inhibitor of cholinesterase and is used for the treatment of Alzheimer's. However, RHT delivery to the brain is limited by the blood–brain barrier (BBB). The purpose of this study was to improve the brain-targeting delivery of RHT by producing and optimizing rivastigmine hydrogen tartrate-loaded tocopherol succinate-based solid lipid nanoparticles (RHT-SLNs). RHT-SLNs were prepared using the microemulsion technique. The impact of significant variables, such as surfactant concentration and drug/lipid ratio, on the size of RHT-SLNs and their drug loading and encapsulation efficiency was analysed using a five-level central composite design (CCD). The minimum size of particles and the maximum efficiency of loading and encapsulation were defined according to models derived from a statistical analysis performed under optimal predicted conditions. The experimental results of optimized RHT-SLNs showed an appropriate particle size of 15.6?nm, 72.4% drug encapsulation efficiency and 6.8% loading efficiency, which revealed a good correlation between the experimental and predicted values. Furthermore, in vitro release studies showed a sustained release of RHT from RHT-SLNs.