离子凝胶法制备壳聚糖纳米粒的影响因素研究

目的 探讨离子凝胶法制备壳聚糖纳米粒(CS-NPs)的影响因素.方法 用碱降解法制备高脱乙酰度的壳聚糖(CS),并以之为材料,采用离子凝胶法制备CS-NPs,以微粒的平均粒径、分散度和Zeta电位为指标,考察CS及三聚磷酸钠(TPP)的质量浓度、CS/TPP质量比、CS溶液pH值和CS溶液温度对制备CS-NPs的影响....     

水杨酸脂质体凝胶剂的制备工艺研究

目的制备水杨酸脂质体凝胶并优化制备工艺。方法采用逆相蒸发法制备水杨酸脂质体,以卡波姆为凝胶基质制备水杨酸脂质体凝胶。采用离心法测定脂质体包封率、渗透率,正交实验法优化水杨酸脂质体凝胶剂的制备工艺。结果水杨酸脂质体的包封率为75.86%,渗透率为1.37%;脂质体凝胶的最佳工艺为:卡波姆3g、甘油15g、搅拌温度40℃、搅拌时间15min。结论逆相蒸发法制备水杨酸脂质体,包封率较高,性质稳定;优化后所得产品性状稳定、均一,该法制备水杨酸脂质体凝胶可行。     

胰岛素壳聚糖纳米粒的制备及影响包封率因素的考察

采用离子感胶化法制备亲水性壳聚糖纳米粒。该法制备条件温和，是在下将两种水相混合而形成纳米粒。混合的两相中，其中一相含有壳聚糖和聚氧乙烯，另一相含有聚阴离子三聚磷酸钠。该纳米粒的粒度大小及ζ电位可以通过控制制剂处方组成及工艺进行调节。采用该法制备的胰岛素壳聚糖纳米粒，实验结果表明，胰岛素的包封率可高达90％，且制剂处方及工艺各因素对该纳米粒的包封率有不同程度的影响。该亲水性纳米粒可作为蛋白质或其它能与壳聚糖相互作用的大分子类药物给药系统的载体。     

微乳法制备姜黄素固体脂质纳米粒

目的:制备姜黄素固体脂质纳米粒。方法:微乳法制备姜黄素固体脂质纳米粒。采用伪三元相图法优选微乳三相因素,确定优化条件后,将热微乳分散于冷水中制备固体脂质纳米粒。单因素试验初筛各因素(乳化剂、脂质材料、脂质用量、药脂比、冷水相温度和微乳保温温度)后,以包封率为指标进行正交试验优化处方,并进行验证试验。结果:65℃下由硬脂酸(油相)、聚山梨酯80(乳化剂)、乙醇(助乳化剂)组成三相,乳化剂与助乳化剂比为1∶4所制得的微乳最佳。固体脂质纳米粒的优化处方为姜黄素投药量为50 mg、硬脂酸的用量为0.5 g、冷水相温度为2℃、微乳保温温度为65℃;所得固体脂质纳米粒的包封率为87.73%、载药量为7.72%、粒径为(156.9±2.2)nm、多分散系数为0.480,平均Zeta电位为-24.8 m V(RSD<2%,n=3)。结论:采用微乳法制备固体脂质纳米粒操作简便、可行。     

壳聚糖-甲基丙烯酸甲酯共聚物纳米粒的制备和表征

目的制备壳聚糖-甲基丙烯酸甲酯共聚物纳米粒。方法用自由基聚合法合成壳聚糖-甲基丙烯酸甲酯共聚物,该聚合物在水中形成具有疏水核心、亲水表面的纳米粒。测定纳米粒的形态、粒径和表面电位(Zeta电位),并研究了壳聚糖含量、聚合物总浓度和引发剂浓度对纳米粒粒径的影响。以胰岛素为模型药物,研究纳米粒的包封和释药性能。结果纳米粒呈球形,粒径均匀,表面荷正电。胰岛素的包封率可达90%以上。pH 5.8的磷酸盐缓冲液中胰岛素的释放较慢,16 h释放量为66.8%。结论该纳米制剂具有较好的物理性能和体外缓释特性。     

负载胰岛素壳聚糖接枝醋酸乙烯酯纳米粒的制备和性能

目的:制备负载胰岛素壳聚糖-醋酸乙烯酯共聚物纳米粒并研究其性能。方法:用自由基聚合法合成壳聚糖-醋酸乙烯酯共聚物,该聚合物在水中形成具有疏水核心、亲水表面的纳米粒。采用正交设计试验研究了投料比、引发剂浓度和反应时间对纳米粒粒径的影响。结果:对纳米粒进行了热重分析和红外表征。测定纳米粒的形态、粒径和表面电位(Zeta电位),以胰岛素为模型药物,研究纳米粒的包封和释药性能。结论:纳米粒呈球形,粒径均匀,表面荷正电。胰岛素的包封率可达90%以上。pH6.8的磷酸盐缓冲液中胰岛素释放较慢。结论:该纳米制剂具有较好的物理性能和体外缓释特性。     

载基因壳聚糖纳米粒的制备及其相关性质的研究

目的：制备壳聚糖载基因纳米粒，并对其体外相关性质进行初步研究。方法：采用复凝聚法制备载基因纳米粒；用纳米粒度仪测量粒度分布，分散性和Zeta电位；用透射电镜观察粒子的形态；用紫外分光光度法和比色法测定包封率和载药量，并对主要影响因素进行考察。用凝胶阻滞分析和电性结合分析对载药方式进行初步推测。结果：所制备的载基因纳米粒形态规则，大多呈球形，纳米粒平均粒径为263．2nm，粒径分布较窄，多分散度为0．213，Zeta电位为19．8mV；包封率大于90％，载药量约30％；凝胶阻滞和电性结合分析结果表明，非甲基化胞嘧啶鸟嘌呤的寡核苷酸链（CPG-ODN）与壳聚糖分子间可通过电性结合作用而完全结合。结论：采用复凝聚法可制备粒度分布均匀，形态规则，具有较高包封率和载药量的载基因壳聚糖纳米粒；电性结合作用是载基因壳聚糖纳米粒载药的主要方式。     

小檗碱壳聚糖纳米粒的制备及其体外释药特性研究

目的:制备小檗碱壳聚糖纳米粒,并考察其外观、粒径和体外释药特性。方法:以离子凝胶法制备小檗碱壳聚糖纳米粒,紫外分光光度法测定小檗碱含量并计算其在不同递质中的累积释放度。结果:壳聚糖纳米粒呈球形或类球形,平均粒径267.9nm,多分散系数0.264,平均包封率(65.4±0.7)%。纳米粒6h内释放度为(56.8±1.7)%,8h以后趋于平缓,24h释放度为(65.6±1.1)%;在人工胃液、人工肠液和pH7.4磷酸盐缓冲液3种溶出递质6h内释放度依次为(75.3±1.3)%、(55.7±0.9)%、(45.8±1.6)%。结论:离子凝胶法适用于小檗碱壳聚糖纳米粒的制备,释药递质对释药程度影响显著,呈pH依赖性。     

盐酸环丙沙星壳聚糖纳米粒原位凝胶的制备与评价

目的 制备盐酸环丙沙星壳聚糖纳米粒原位凝胶,并评价其抑菌及创面愈合效果。方法 采用复乳法制备盐酸环丙沙星壳聚糖纳米粒,采用2因素2水平全因子析因实验设计考察了壳聚糖相对分子质量（X₁）和壳聚糖质量浓度（X₂）对壳聚糖纳米粒的药物包封率（Y₁）、粒径分布（Y₂）、多分散系数（Y₃）和Zeta电位（Y₄）的影响;并以泊洛沙姆407作为凝胶基质制备盐酸环丙沙星壳聚糖纳米粒原位凝胶。通过抑菌圈实验比较盐酸环丙沙星乳膏和盐酸环丙沙星壳聚糖纳米粒原位凝胶对金黄色葡萄球菌和铜绿假单胞菌的抑菌活性;使用无菌活检穿刺针在大鼠背部造成直径为5 mm的皮肤全切除的圆形人工创面,并使用金黄色葡萄球菌和铜绿假单胞菌的培养基感染24 h,建立大鼠创面模型,将模型大鼠随机分为模型组、盐酸环丙沙星乳膏组和盐酸环丙沙星壳聚糖纳米粒原位凝胶组,模型组大鼠创面未接受任何处理,给药组大鼠每2天给药1次,每次给药量均约为1 mg,观察并记录每组大鼠创面脱痂时间和愈合时间。结果 选择低相对分子质量壳聚糖、壳聚糖质量浓度为2.0 mg·mL^-1制备盐酸环丙沙星壳聚糖纳米粒,其中盐酸环丙沙星质量浓度为50.0 mg·mL^-1,其包封率为（85.3±0.9）%,平均粒径为（354.7±15.7）nm,PDI为0.357±0.014,Zeta电位为（22.2±0.5）mV,呈球状分布;盐酸环丙沙星壳聚糖纳米粒原位凝胶和盐酸环丙沙星乳膏对金黄色葡萄球菌的抑菌圈直径分别为（38.4±0.2）、（29.2±0.3）mm,对铜绿假单胞菌抗菌圈直径分别为（41.3±0.6）、（32.1±0.1）mm;大鼠创面给予盐酸环丙沙星壳聚糖纳米粒原位凝胶后,其脱痂时间和愈合时间均较模型组和盐酸环丙沙星乳膏组显著缩短（P<0.05）。结论 成功制备盐酸环丙沙星壳聚糖纳米粒原位凝胶,其可以抑制创面细菌繁殖、加速伤口愈合。     

载基因壳聚糖纳米粒的制备及其相关性质的初步研究

目的制备壳聚糖载基因纳米粒,并对其体外相关性质进行初步研究。方法采用复凝聚法制备载基因纳米粒;用纳米粒度仪测量粒度分布、多分散性和Zeta电位;用透射电镜观察粒子的形态;用荧光分光光度法和比色法测定包封率和载药量,并对主要影响因素进行考察;用凝胶阻滞分析和电性结合分析对载药方式进行初步推测。结果所制备的载基因纳米粒形态规则,大多呈球形,平均粒径约150nm,PDI＜0．2,Zeta电位约20mV;包封率大于90％,载药量约30％;凝胶阻滞和电性结合分析结果表明,pDNA与壳聚糖分子间可通过电性结合作用而完全结合。结论采用复凝聚法可制备粒度分布均匀,形态规则,具有较高包封率和载药量的载基因壳聚糖纳米粒;电性结合作用是载基因壳聚糖纳米粒载药的主要方式。     

季铵化壳聚糖胰岛素纳米粒的制备、处方优化及其初步药效学实验

目的 采用正交设计试验优化载胰岛素季铵化壳聚糖纳米粒的处方工艺,并初步考察其降糖效果。 方法 用离子交联法制备载胰岛素的季铵化壳聚糖纳米粒,用正交试验确定其最佳处方工艺。用透射电子显微镜观察纳米粒的表面形态;用粒径/Zeta电位仪测定纳米粒的粒径和Zeta电位;用高效液相色谱(HPLC)法测定纳米粒的包封率、载药量及体外释放情况。对糖尿病大鼠皮下注射给药,对其药效学进行初步考察。 结果 制得的纳米粒呈球形,分布均匀;平均粒径(63.26±1.88) nm;Zeta电位(33.1±0.3) mV;包封率(37.92±2.11)%;载药量(5.42±0.3)%;24 h累计释放率63.83%。皮下注射给药8 h,糖尿病大鼠血糖较单纯注射胰岛素组下降平缓,且药效持久。 结论 优化后的载胰岛素的季铵化壳聚糖纳米粒形态较好、粒径较小,为研究胰岛素的新型给药途径奠定了基础。     

三甲基化壳聚糖卵清蛋白纳米粒的制备

目的：以N-三甲基壳聚糖盐酸盐（N—trimethyl chitosan chloride，TMC）为材料制备新型纳米粒（nanoparticles，NPs），包裹卵清蛋白（ovalbumin，OVA），以提高卵清蛋白的包封率。方法：利用TMC与三聚磷酸钠（tripolyphosphatesodium，TPP）之间的离子胶凝作用制备纳米粒；用纳米粒度及表面电位分析仪测定纳米粒的粒径及zeta电位；探讨OVA溶液的pH值及浓度，TMC溶液的浓度，TPP溶液的浓度等因素对OVA包封率的影响；用十二烷基硫酸钠一聚丙烯酰胺明胶电泳（Soldium Dodeoyl Sulfate—Polyacrylamide，SDS-PAGE）检验OVA在纳米粒制备及体外释放过程中有无降解。结果：本研究制备的TMC／OVA纳米粒为紧密球形，分布均匀，粒径约为135．4nm，zeta电位约为＋20mV；OVA的pH值及制备工艺是影响包封率的主要因素；SDS-PAGE电泳证实在纳米粒的制备及释放过程中OVA没有降解。结论：用离子胶凝法制备载蛋白多肽类疫苗的纳米粒，操作简便，采用合适的制备方法，调整处方可将包封率提高到90％以。     

用离子交联-匀化工艺制备乙肝疫苗壳聚糖纳米粒

目的：研究制备乙肝疫苗壳聚糖（chitosan，CS）纳米粒的适宜条件和影响因素。方法：以CS溶液和三聚磷酸钠溶液，采用离子交联-高压匀化工艺制备乙肝疫苗壳聚糖纳米粒，考察CS的浓度、CS与二聚磷酸钠的质量比及高压匀化对壳聚糖纳米粒粒径和多分散系数的影响，测定了载药纳米粒的包封率和载药量。结果：当CS与三聚磷酸钠的浓度都为2mg/mL，质量比为3：1～6：1，通过离子交联-高压匀化工艺可以得到稳定的纳米粒。纳米粒外观圆整，粒径分布均匀，包封率达到90％以上。结论：用离子交联－高压匀化工艺制备CS纳米粒不需要使用有机溶剂，包封率较高，可以满足给药系统应用要求。     

左旋多巴固体脂质纳米粒的制备及包封率测定

目的:用微乳法制备左旋多巴固体脂质纳米粒(LDP-SLN),并建立包封率的测定方法。方法:通过绘制三元相图,采用微乳法制备LDP-SLN,用TEM和激光粒度仪进行了颗粒形貌和粒径分布的研究,用葡聚糖凝胶层析法分离测定包封率。对其粒径、形态、包封率等理化性质进行研究,并考察其稳定性。结果:实验制得LDP-SLN为稳定的略泛蓝色乳光的纳米混悬液,在透射电镜下显示为较为均匀的球体,激光粒度测定平均粒径为108nm,多分散系数1.153;4℃放置2个月,粒径、包封率无显著变化。包封率测定的线性范围为2～100mg·mL-1,线性良好(r=0.9999),精密度符合要求,LDP-SLN上柱洗脱后分离度和回收率均符合要求。结论:该研究中制备了物理性质较为稳定的LDP-SLN,建立了合适的包封率测定方法,并考查初步稳定性较好。     

Preparation,characterization, and antibacterial activity of diclofenac-loaded chitosan nanoparticles

Emerging antibiotic resistance necessitates the development of new therapeutic approaches. Many studies have reported the antimicrobial activity of diclofenac sodium (DIC) and chitosan nanoparticles (CNPs). Hence, this study aimed to prepare non-antibiotic DIC-loaded CNPs (DIC.CNPs) and characterize their in vitro antibacterial activity. DIC.CNPs were prepared from low and high molecular weight (LMW and HMW, respectively) chitosan using an ionic gelation method. Prepared NPs were characterized, and their antibacterial activity against gram-positive Staphylococcus aureus and Bacillus subtilis was evaluated using the agar diffusion and broth dilution methods. The particle size, polydispersity index (PDI), and encapsulation efficiency of the formulated DIC.CNPs increased with increasing MW of chitosan. The prepared NPs showed a narrow size distribution with low PDI values (0.18 and 0.24) and encapsulation efficiency (29.3% and 31.1%) for LMW.DIC.CNPs and HMW.DIC.CNPs, respectively. The in vitro release profile of DIC from the DIC.CNPs was biphasic with a burst release followed by slow release and was influenced by the MW of chitosan. DIC.CNPs exhibited significantly higher antibacterial activity against S. aureus (minimum inhibitory concentration [MIC₉₀] _LMW.DIC.CNPs?=?35?µg/mL and MIC_{90 HMW.DIC.CNPs}?=?18?µg/mL) and B. subtilis (MIC_{90 LMW.DIC.CNPs}?=?17.5?µg/mL and MIC_{90 HMW.DIC.CNPs}?=?9?µg/mL) than DIC alone did (MIC_{90 DIC}?=?250 and 50?µg/mL against S. aureus and B. subtilis, respectively). The antibacterial activity was influenced by pH and the MW of chitosan. Collectively, these results may suggest the potential usefulness of DIC.CNPs as non-antibiotic antibacterial agent necessitating further future studies to asses the stability of DIC.CNPs prepared.     

叶酸修饰的粉防己碱壳聚糖纳米粒制备工艺的研究

目的:研究叶酸修饰的粉防己碱(tetrandrine, TET)壳聚糖纳米粒(TET/FA-CSO-NPs)的最佳制备工艺并进行质量评价。方法:以离子交联法制备TET/FA-CSO-NPs,通过单因素及正交试验优化处方组成并确定最佳制备工艺,通过形态观察、粒径、载药量及包封率的考察对其进行质量评价。以MTT法分别检测TET和TET/FA-CSO-NPs作用于人肝癌HepG2细胞的增殖抑制作用,并计算半数抑制浓度(IC₅₀)。结果:最佳制备工艺为叶酸-壳聚糖偶联物(FA-CSO)1.50 mg·mL^-1,TPP浓度2.50 mg·mL^-1,载药质量比为1∶1,制备的TET/FA-CSO-NPs粒径为(214.9±2.1) nm, Zeta电位为(35.2±1.3) mV,包封率为(89.49±1.21)%,载药量为(24.41±0.33)%,外观圆整、均匀。FA-CSO空白纳米粒的质量浓度达到800μg·mL^-1时细胞的存活率为(83.08±9.23)%,TET,TET/CSO-NPs和TET/FA-...     

Preparation and in vitro/in vivo evaluation of resveratrol-loaded carboxymethyl chitosan nanoparticles

Resveratrol (RES) is natural polyphenol with a strong biological activity, but its disadvantages, such as poor water solubility, susceptibility to oxidative decomposition and rapid metabolism in the body, which substantially restricts in vivo bioavailability, need to be resolved. This study used carboxymethyl chitosan (CMCS) as a drug carrier and utilized emulsion cross-linking to prepare RES-loaded CMCS nanoparticles (RES-CMCSNPs). A single-factor experiment was performed to optimize the preparation of these particles; in vitro and in vivo characteristics were evaluated. Spherical RES-CMCSNPs were prepared under optimal conditions, in which average particle size, potential, drug loading and encapsulation efficiency were (155.3?±?15.2) nm, (?10.28?±?6.4) mV, (5.1?±?0.8)% and (44.5?±?2.2)%, respectively. FTIR, DSC and XRD showed that RES molecules were wrapped in the nanoparticles. In vitro DPPH radical scavenging abilities showed RES-CMCSNPs were better than RES raw powder. The nanoparticles improved the solubility of RES, thereby greatly improving the antioxidant activity of the drug. In vitro release experiments of RES and RES-CMCSNPs by simulating the human gastrointestinal tract were performed, in which RES-CMCSNPs rendered better releasing effects than raw RES. Raw RES and RES-CMCSNPs results were in line with those obtained for the single-chamber model for pharmacokinetic studies in rats. Compared with the bulk drugs, the RES-CMCSNPs exhibited increased in vivo absorption, prolonged duration of action and increased relative bioavailability by 3.516 times more than those of the raw RES. In addition, the residual chloroform is less than the ICH limit for class 2 solvents.     

Preparation of endostatin-loaded chitosan nanoparticles and evaluation of the antitumor effect of such nanoparticles on the Lewis lung cancer model

The purpose of this study was to prepare ES-loaded chitosan nanoparticles (ES-NPs) and evaluate the antitumor effect of these particles on the Lewis lung cancer model. ES-NPs were prepared by a simple ionic cross-linking method. The characterization of the ES-NPs, including size distribution, zeta potential, loading efficiency and encapsulation efficiency (EE), was performed. An in vitro release test was also used to determine the release behavior of the ES-NPs. Cell viability and cell migration were assayed to detect the in vitro antiangiogenic effect of ES-NPs. In order to clarify the antitumor effect of ES-NPs in vivo, the Lewis lung cancer model was used. ES-NPs were successfully synthesized and shown to have a suitable size distribution and high EE. The nanoparticles were spherical and homogeneous in shape and exhibited an ideal releasing profile in vitro. Moreover, ES-NPs significantly inhibited the proliferation and migration of human umbilical vascular endothelial cells (HUVECs). The in vivo antiangiogenic activity was evaluated by ELISA and immunohistochemistry analyses, which revealed that ES-NPs had a stronger antiangiogenic effect for reinforced anticancer activity. Indeed, even the treatment cycle in which ES-NPs were injected every seven days, showed stronger antitumor effect than the free ES injected for 14 consecutive days. Our study confirmed that the CS nanoparticle is a feasible carrier for endostatin to be used in the treatment of lung cancer.     

Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method

In the past decade, many strategies have been developed to enhance oral protein delivery. The aim of the current work was to develop a nanoparticulate system based on ionic gelation between chitosan and Arabic gum for loading of insulin. Various formulations were prepared using 2³ factorial designs. The optimum association efficiency was obtained for formulations F2, F5, and F8. The release profile of insulin in phosphate buffer solutions (pH 6.5 and pH 7.2) is completely different than that in acidic medium (pH 1.2). Increased solubility of chitosan in acidic medium and better swelling of Arabic gum chains at pH >6.5 resulted in lower insulin release of nanoparticles at pH 6.5 in comparison with that of the other pH mediums. The values of the exponent n were 0.49 and 0.82 for formulations F8 and F5, respectively, indicating a non-Fickian transport. This suggests that release is possibly controlled by diffusion or relaxation of the polymer chains.From the Clinical EditorThis paper summarizes the development of a nanoparticulate system based on ionic gelation between chitosan and gum Arabic for oral delivery of insulin. If preclinical studies in animal models will indicate reliable and quantifiable delivery of insulin, this method may pave the way to a novel and less invasive way of administering insulin to diabetes patients.