PLGA微球包埋药物的稳定性及释放研究的新进展

乳酸-乙醇酸共聚物[ poly( lactide-co-glycolide),PLGA]是一种前景良好的可降解合成高分子材料,作为缓释给药系统的基体材料被广泛研究.这主要基于其优异的生物相容性、可调控的生物降解性,以及已被欧美药监局批准等优点.微球缓释给药可延长药物的半衰期,增加临床治疗效果,在医药行业和生物材料领域备...     

负载二甲酸钾缓释抗菌微球的构建

为避免二甲酸钾(KDF)在酸性环境下分解过快,调节仔猪肠胃道酸碱性和菌落平衡,实现KDF靶向释放抗菌,本研究以可生物降解的壳聚糖(CS)、羧甲基纤维素(CMC)和无机刚性材料P型沸石分子筛(Zeolite P)为载体,负载抗菌药物二甲酸钾制备控释水凝胶微球。发现CS中–NH2与CMC中–COOH离子作用,可形成结构稳定的聚电解质复合物。溶胀率的差异性表明CS/CMC/ZeoliteP水凝胶微球对pH高度敏感。加入ZeoliteP使水凝胶微球在pH1.2保持原有形貌且不被降解破裂。CS/CMC/Zeolite P/KDF抗菌微球的包封率为47.75%,载药率为23.88%,可有效缓释KDF,在p H7.4磷酸盐缓冲溶液中的缓释性比p H1.2更优。CS/CMC/Zeolite P/KDF抗菌微球浓度为96 mg/mL时对大肠杆菌最大抑菌率为83%,有效提高了KDF利用率。     

超临界CO2抗溶剂法制备紫杉醇缓释微球

采用超临界流体强制分散溶液技术,以D,L-聚乳酸和D,L-聚乳酸-聚乙二醇共聚物为载体材料,分别制备了紫杉醇缓释微球.通过扫描电镜、激光粒度仪检测微球外形及粒径分布;紫外吸光度法测量其载药量和包封率,恒温振荡透析法检测药物的体外释放性能;MTT法检测载药微球对Hela细胞的抑制作用.实验表明,两种载体的缓释微球球形度均较好,表面光滑,平均粒径较小,且粒径分布较窄.以聚乳酸和共聚物为载体的缓释微球载药量分别为5.4%±0.3%和5.3%±0.4%,包封率分别为51%±3%和45%±3%;药物释放呈缓释模式,共聚物载药微球药物释放速率较快.MTT法检测结果表明,载药微球对Hela细胞的增殖有明显抑制,共聚物载药微球对细胞增殖抑制更为明显.     

木质素酚醛基载药微球的制备及缓释性能

以工业碱木质素、苯酚和甲醛为主要壁材,采用反相乳液聚合法制备了木质素酚醛基阿维菌素微球。通过扫描电镜、红外光谱、比表面及孔结构分析仪对微球结构进行表征,着重研究了壁材中木质素含量对微球结构和释放性能的影响。结果表明,制得的微球表面形貌呈粗糙球形,粒径在50μm~100μm,分布均匀。木质素含量较高时,微球表面结构较疏松,孔隙较多,释放速度较快。木质素含量约50%时得到的载药微球具有较致密的表面结构,在80%(体积分数)甲醇水溶液中,20 h内的释放率近40%,具有明显的缓释效果。     

载药壳聚糖缓释微球的制备及其释放研究

实验采用乳化交联法,使用复合交联剂(先用甲醛交联,再用戊二醛交联),制得盐酸四环素壳聚糖缓释微球,并考察不同分子量的壳聚糖、原料质量比、交联剂用量、复合交联剂用量、搅拌速度对微球的影响,筛选出最佳条件制备出戢药微球,并研究了该微球在扫描电镜和倒置式研究型显微镜下的形态及其在pH=7.4,温度为37℃时的释放规律.结果表明,采用复合交联剂的乳化交联法所制得的微球球形好,粒径分布为5～50μm之间,载药量为26.9%,包封率为56.3%,并且具有良好的缓释效果.     

功能型多孔聚合物微球的制备及其缓释性能研究

利用超声分散改进的二步溶胀法制备4～9μm的聚苯乙烯-二乙烯苯(PSt-DVB)多孔微球,并以防晒剂parsol 1789为模型组分考察了其缓释性能.通过SEM和BET等手段表征微球表面形貌和孔结构,并研究了超声分散时间、种球类型、交联单体浓度等因素对微球性能的影响.确认超声分散的应用可以明显缩短溶胀时间;种球的粒径和分子量受分散介质极性影响较大,种球的单分散性直接决定最终粒子的形貌;随交联单体浓度增大,微球比表面积上升、孔径下降.制得的多孔聚合物微球用作化妆品活性物载体时,具有良好的缓释作用.     

超细玻璃微球的理化特性及复合化玻璃微球的研究

本文较系统地研究了一种超细玻珠的化学成份，矿物组成，谱学特性及表面电性等，并简介了无机－无机－无机－无机－有机复合玻璃微球的研制。     

壳聚糖靶向缓释功能高分子载药微球及其特性研究

采用壳聚糖作为载体,通过分子结构设计,以叶酸靶向受体改性壳聚糖,然后选择5-氟尿嘧啶为模型药物,采用复凝聚法制备新型壳聚糖靶向缓释功能高分子载药微球。通过红外光谱和1 H-NMR核磁共振分析确定了叶酸改性壳聚糖化学结构,并通过扫描电镜、激光粒度分析仪、激光共聚焦显微镜及紫外光谱等现代仪器和分析方法对载药微球的形貌结构、粒径、包埋率、载药量和体外药物释放特性等进行研究。结果表明,模型药物被成功包埋到叶酸改性后的壳聚糖微球中,包埋率E和载药量L最高可达86.5%和32.7%,载药微球的平均粒径为5.251μm,多分散系数(PDI)为0.056,球形度、分散性良好;激光共聚焦显微镜结果显示微球为核壳结构;体外释放实验表明壳聚糖靶向缓释功能高分子载药微球具有持久的缓释作用,24h后载药微球在模拟胃液(pH值=1.2)中释放率为70%,在模拟肠液(pH值=7.4)中释放率为40%,释药速度与释放介质的pH值密切相关。     

中空层状羟基磷灰石微球对溶菌酶的吸附与缓释研究

利用锂钙硼玻璃在磷酸盐溶液中的原位转化反应制备表面多孔且具有中空层状结构的羟基磷灰石(HA)微球,以溶菌酶为蛋白的药物模型,研究了中空层状结构的羟基磷灰石微球对溶菌酶的吸附及缓释特性,结果显示,中空微球对不同浓度的溶菌酶溶液,具有不同的吸附机理,当溶菌酶溶液的浓度低于0.8mg/mL时,溶菌酶的吸附主要发生在微球的外表面,符合Langmuir模型,释放速率较快,48h内基本释放完全;当溶菌酶溶液的浓度高于0.8mg/mL时,溶菌酶扩散进入微球内部及球壁的微孔中,使得吸附量显著增加,满足Henry吸附模型,溶菌酶的释放周期明显增加,可持续释放800h,微球对蛋白具有很好的缓释效果。     

纳米结构的空腔二氧化硅微球的制备与缓释行为

以单分散聚苯乙烯(PS)微球作为胶体模板,采用层层静电自组装技术,交替组装聚电解质聚二烯丙基二甲基氯化铵[poly(diallyldimethylammonium chloride),PDDA]和二氧化硅纳米颗粒(10和20nm),得到核壳型聚苯乙烯/聚电解质/二氧化硅复合微球,高温煅烧除去模板PS和聚电解质,制得空腔二氧化硅微球.TEM观察的结果显示空腔二氧化硅微球呈单分散性且内部空腔呈球形;XRD图谱显示组装的二氧化硅颗粒热处理后晶化的程度很小,仍基本保持着无定形状态;N₂等温吸附-脱附实验测得用10和20nm的二氧化硅组装成的空腔二氧化硅微球的平均孔径和比表面积分别为11nm、282.71m²·g^-1和15nm、158.17m²·g^-1. 染料的装载和释放实验分别验证了空腔二氧化硅微球的腔壁具有可渗透性和缓释性.     

基于凝固浴剪切法制备多孔实心聚(乳酸-羟基乙酸)共聚物载药微球

以聚(乳酸-羟基乙酸)为基质材料,采用一种新颖的流动凝固浴剪切法制备包载盐酸万古霉素的载药微球,并研究微球的形貌结构、粒径、包封率、载药率、体外释放性能及其影响因素。结果表明,所制备的载药微球平均粒径在15~29μm范围,微球呈现内部实心表面多孔的复合结构;微球的包封率及载药可分别在15%~75%和1.5%~9.3%范围内调控。微球制备过程中的工艺条件对微球结构形貌、包封率、载药率及释放性能有重要影响,通过调整微球的粒径,可有效减缓释药过程中的突释现象。     

PLA、PGA及其共聚物在包装领域应用研究进展

目的 综述聚乳酸(PLA)、聚乙交酯(PGA)、聚乙丙交酯(PLGA)及其改性材料在包装领域的研究进展,对改性材料及制备工艺进行展望,为PLA、PGA以及PLGA的改性与制备提供参考。方法 简介PLA、PGA以及PLGA的制备方法、基本性能,并总结近几年改性材料的种类及其制备工艺。结果 对PLA、PGA以及PLGA进行改性,再通过溶液铸膜、吹塑制膜等工艺制备薄膜,制备的薄膜具有优异的抗紫外性能、阻隔性能以及抗菌性能。结论 PLA、PGA以及PLGA具有优异的生物降解性能,通过改性后制备的薄膜性能更加均衡,在包装领域具有极大的应用前景,对聚合物的改性方法还需进行深入研究,制备出性能更加优异的改性材料。     

CdSe-ZnS QDs/PLGA纳米复合材料的性能及体外降解行为

采用溶液浇铸法制备了不同CdSe-ZnS量子点(Quantum dots QDs)含量的QDs/乳酸-乙醇酸共聚物(PLGA)复合材料薄膜,通过傅里叶变换红外光谱仪、透射电子显微镜(TEM)、光致发光光谱仪(PL)及紫外-可见吸收光谱仪(UV-Vis)等对薄膜的微观结构与光学性能进行了表征,并对不同降解时间后降解液的pH值、薄膜的发光情况和相对分子质量及其分布进行了测试。PL及UV-Vis结果显示,QDs/PLGA纳米复合材料的发光性能良好,吸光度随QDs含量增加而增大;TEM结果显示,QDs在基体中分散良好;在体外降解过程中,凝胶渗透色谱和缓冲液p H值测试结果说明,量子点催化了PLGA的降解;复合材料的荧光效应随着降解时间的延长逐渐减弱。以上结果说明,采用简单的溶液浇铸法制备的CdSe-ZnS QDs/PLGA复合材料发光性能稳定优异,且可以通过检测荧光效应变化以实现动态监测QDs/PLGA复合材料的降解进程。     

Tracking the effect of microspheres size on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot in vitro and in vivo

The effects of particle size of microspheres on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot (m-SAIB) was investigated to develop a long-term sustained release drug delivery system with low burst release both in vitro and in vivo. A model drug, risperidone, was first encapsulated into PLGA microspheres with different particle sizes using conventional emulsification and membrane emulsification methods. The m-SAIB was prepared by dispersing the risperidone-microspheres in the SAIB depot. The drug release from m-SAIB was double controlled by the drug diffusion from the microspheres into SAIB matrix and the drug diffusion from the SAIB matrix into the medium. Large microspheres (18.95?±?18.88?µm) prepared by the conventional homogenization method exhibited porous interior structure, which contributed to the increased drug diffusion rate from microspheres into SAIB matrix. Consequently, m-SAIB containing such microspheres showed rapid initial drug release (C_max?=_?110.1?±54.2?ng/ml) and subsequent slow drug release (C_s(4–54d)=?2.7?±?0.8?ng/ml) in vivo. Small microspheres (5.91?±?2.24?µm) showed dense interior structure with a decreased drug diffusion rate from microspheres into SAIB matrix. The initial drug release from the corresponding m-SAIB was significantly decreased (C_max?=_?40.9?±?13.7?ng/ml), whereas the drug release rate from 4 to 54 d was increased (C_s(4–54d)=4.1?±?1.0?ng/ml). By further decreasing the size of microspheres to 3.38?±?0.70?µm, the drug diffusion surface area was increased, which subsequently increased the drug release from the m-SAIB. These results demonstrate that drug release from the m-SAIB can be tailored by varying the size of microspheres to reduce the in vivo burst release of SAIB system alone.     

PLGA/TSF静电纺纳米纤维的仿生矿化及生物相容性

利用静电纺丝和模拟体液仿生矿化技术制备了聚乳酸-羟基乙酸共聚物/柞蚕丝素/羟基磷灰石((PLGA/TSF/HA)骨组织工程复合支架。通过扫描电子显微镜(SEM)、透射电子显微镜(TEM)、X射线衍射测试(XRD)和热重分析(TG)对复合纳米纤维的形貌结构进行了表征。此外,在复合纳米纤维支架材料上接种人骨髓间充质干细胞(hMSCs),通过四甲基偶氮噻唑蓝比色(Four methyl azo thiazole blue colorimetric,MTT)法,观察细胞在材料表面的生长情况评价纳米纤维的生物相容性。结果显示,PLGA/TSF纳米纤维毡具有精细的三维结构,纤维直径分布均匀,表面光滑。矿化后HA颗粒均匀地分布在PLGA/TSF纳米纤维表面,矿物含量约占63%。与PLGA/TSF纳米纤维支架相比,PLGA/TSF/HA纳米纤维支架的亲水性、生物相容性都得到显著提高。     

可降解聚碳酸亚丙酯马来酸酯载药微球的制备

采用阴离子配位聚合方法,合成了二氧化碳(CO2),环氧丙烷(PO)与马来酸酐(MA)的三元共聚物,聚碳酸亚丙酯马来酸酯 (PPCMA).采用复相乳液(W/O/W)溶剂挥发法制备了包裹水溶性模型药物葡萄糖(glucose)的可降解微球,并研究了壁材与囊心的比例、稳定剂明胶浓度、搅拌速率等因素对微球性能的影响.当v(PPCMA)∶v(glucose)=1∶2,gelatin质量分数为0.2%,第1次乳化搅拌速率为400r/min,第2次乳化搅拌速率为500r/min时,得到粒径较小、载药量和包封率分别为26.1%和76.1%的载药微球.     

超临界流体技术制备5-氟尿嘧啶-吲哚美辛-聚乳酸缓释微球

为了考察药物5-氟尿嘧啶(5-Fu)与吲哚美辛(IDMC)的协同作用, 采用超临界流体强制分散溶液技术(SEDS), 以二氯甲烷/二甲亚砜为共溶剂, 制备了复合5-Fu和IDMC的L-聚乳酸(PLLA)微球。利用单因素法探索了制备复合微球的最佳外部条件, 通过表面形貌、 载药量、 粒径分布、 释放性能的检测和体外细胞实验来表征微球的各项性能。结果表明: 当共溶剂二氯甲烷/二甲亚砜比例为30∶1时, 制备该微球的优化条件为39℃、 14MPa; 微球形貌呈类球形, 粒径分布在0.5~5μm; 复合IDMC后微球具有更优良的缓释效果; 载药微球对A549细胞系增殖有明显的抑制作用, 但与复合IDMC前后微球共培养的2组细胞的相对生长速率(RGR)无显著性差异。      

A Self-Disguised Nanospy for Improving Drug Delivery Efficiency via Decreasing Drug Protonation

Nanoscale drug carriers play a crucial role in reducing side effects of chemotherapy drugs. However, the mononuclear phagocyte system (MPS) and the drug protonation after nanoparticles (NPs) burst release still limit the drug delivery efficiency. In this work, a self-disguised Nanospy is designed to overcome this problem. The Nanospy is composed of: i) poly (lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) loading doxorubicin is the core structure of the Nanospy. ii) CD47 mimic peptides (CD47p) is linked to NPs which conveyed the “don't eat me” signal. iii) 4-(2-aminoethyl) benzenesulfonamide (AEBS) as the inhibitor of Carbonic anhydrase IX (CAIX) linked to NPs. Briefly, when the Nanospy circulates in the bloodstream, CD47p binds to the regulatory protein α (SIRPα) on the surface of macrophages, which causes the Nanospy escapes from phagocytosis. Subsequently, the Nanospy enriches in tumor and the AEBS reverses the acidic microenvironment of tumor. Due to above characteristics, the Nanospy reduces liver macrophage phagocytosis by 25% and increases tumor in situ DOX concentration by 56% compared to PLGA@DOX treatment. In addition, the Nanospy effectively inhibits tumor growth with a 63% volume reduction. This work presents a unique design to evade the capture of MPS and overcomes the influence of acidic tumor microenvironment (TME) on weakly alkaline drugs.     

Development and evaluation of hollow mesoporous silica microspheres bearing on enhanced oral delivery of curcumin

The aim of this work is to develop curcumin-loaded hollow mesoporous silica microspheres (HMSMs@curcumin) to improve the poor oral bioavailability of curcumin. Hollow mesoporous silica microspheres (HMSMs) were synthesized in facile route using a hard template. HMSMs and HMSMs@curcumin were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption measurements, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). In addition, to demonstrate the potential application of the HMSMs@curcumin, cytotoxicity, in vitro release behavior and in vivo pharmacokinetics of curcumin loaded in these HMSMs were investigated by using of Caco-2 cells and Sprague-Dawley (SD) rats, respectively. These mono-dispersed HMSMs exhibited high drug loading ratio and encapsulation efficiency due to the mesoporous shell and hollow core. The excellent characteristics of HMSMs such as mono-dispersed morphology, smooth surface, uniform, ordered and size-narrowing mesopores resulted in a good in vitro release profile of curcumin from HMSMs@curcumin. Moreover, an impressive improvement in the oral absorption of curcumin and prolonged systemic circulation time were achieved in the in vivo animal studies. In addition, the good biocompatibility of developed HMSMs with Caco-2 cells was confirmed based on the in vitro cytotoxicity assay. In conclusion, this system demonstrated a great potential for efficient delivery of curcumin in vitro and in vivo, suggesting a good prospect for its application in clinic for therapeutic drug delivery in future.     

Mucoadhesive plasticized system of branched poly(lactic-co-glycolic acid) with aciclovir

Commercially available antibacterial semisolid preparations intended for topical application provide only short-term drug release. A sustained kinetics is possible by exploitation of a biodegradable polymer carrier. The purpose of this work is to formulate a mucoadhesive system with aciclovir (ACV) based on a solid molecular dispersion of this drug in poly(lactic-co-glycolic acid) branched on tripenterythritol (PLGA/T). The ACV incorporation into PLGA/T was carried out either by solvent method, or melting method, or plasticization method using various plasticizers. The drug–polymer miscibility, plasticizer efficiency and content of residual solvent were found out employing DSC. Viscosity was measured at the shear rate range from 0.10 to 10.00?s^?1 at three temperatures and data were analyzed by Newtonian model. The mucoadhesive properties were ascertained in the tensile test on a mucin substrate. The amount of ACV released was carried out in a wash-off dissolution test. The DSC results indicate a transformation of crystalline form of ACV into an amorphous dissolved in branched polyester carrier, and absence of methyl formate residuals in formulation. All the tested plasticizers are efficient at T_g depression and viscosity decrease. The non-conventional ethyl pyruvate possessing supportive anti-inflammatory activity was evaluated as the most suitable plasticizer. The ACV release was strongly dependent on the ethyl pyruvate concentration and lasted from 1 to 10 days. The formulated PLGA/T system with ACV exhibits increased adhesion to mucosal hydrophilic surfaces and prolonged ACV release controllable by degradation process and viscosity parameters.