白藜芦醇纳米载体的制备与表征

制备了负载1%白藜芦醇（Res）的三种脂质纳米载体,分别为固体脂质纳米粒（SLN）、纳米脂质载体（NLC）和纳米乳（NE）,通过进行离心、粒径、zeta电位、pH值、含量、包封率及对温度的稳定性等理化性质研究,结果表明,Res-SLN,粒径45±5nm,zeta电位-10.0±0.3mV,含量为9.57mg.mL-1,包封率为98.68%;Res-NLC,粒径185±3nm,zeta电位-10.8±0.5mV,含量为9.17mg.mL-1,包封率为99.36%;Res-NE,粒径7nm,zeta电位-4.8±0.4mV,含量为9.89mg.mL-1,包封率为97.97%。三种载体体系在4℃及25℃离心10000r/min,30min不分层。分别在室温、4℃、40℃下放置15d,Res-NLC表现出良好的稳定性。     

近红外荧光磁性复合载药脂质体的制备及应用

拟建立以近红外荧光磁性复合脂质体(NFMSLs)为模型药物载体、盐酸多柔比星(DOX)为包封药物的药物输送系统,研究了近红外荧光磁性载药复合脂质体(DOX-NFMSLs)的制备、性质及初步应用。采用共沉淀法制备Fe3O4磁流体,CdTe掺杂Se制备近红外量子点CdSeTe,薄膜分散法制备DOX-NFMSLs。用DOX荧光分光光度法测定DOX-NFMSLs的包封率和体外药物释放率;用DOX-NFMSLs与HepG2肝癌细胞共孵育来进行细胞成像和细胞毒性实验。结果表明,近红外CdSeTe量子点粒径约为5nm,闪锌矿结构,发射波长824nm。磷脂与胆固醇质量比为8∶1,药脂比为1∶20的DOX-NFMSLs平均粒径为252.9nm,Zeta电位为-48.6mV,理想释放药物温度为41℃,平均包封率为(74.84±0.89)%。DOX-NFMSLs对HepG2肝癌细胞有一定的抗癌效果。得到了具有良好磁响应、释药温度T=41℃、可近红外成像的载药脂质体。     

甘草酸羧甲基壳聚糖纳米粒的制备及其性能研究

通过正交试验设计优化钙离子交联法制备羧甲基壳聚糖纳米粒工艺条件,以透射电镜观察,纳米粒外观形态圆整;以激光粒度分析仪测定,纳米粒平均粒径为(131.2±5.27)nm;以高效液相色谱法测定,纳米粒包封率为(51.2±0.41)%,载药量为(16.7±0.29)%。对模型药物甘草酸的体外释放性能考察结果表明,所制备的纳米粒具有较好的控制药物释放的作用。     

甜玉米芯多糖纳米乳微胶囊制备及释放

目的 改善甜玉米芯多糖(SCP)大分子特性以及稳定性,促进SCP的肠道吸收。方法 将SCP水溶液制备成油包水型(W/O)甜玉米芯多糖纳米乳液(SCP-NE),以复合蛋白为壁材制备成SCP-NE微胶囊,采用单因素试验、Box-Behnken设计和响应面法优化SCP-NE微胶囊制备工艺,以粒径分析、红外光谱分析、热重分析,对SCP-NE微胶囊物化性质进行研究,并进行体外模拟胃肠液释放研究。结果 制备SCP-NE微胶囊最佳条件为麦芽糊精(MD)与大豆分离蛋白(SPI)的质量比为2∶3、芯壁比为1∶2、总体固形物含量为20%,此时包封率达到(87.6±1.3)%。体外模拟胃肠液释放结果表明,SCP-NE微胶囊在2 h的胃液消化中释放率为8.83%,在模拟肠液中1 h的释放量为62.87%。结论 以MD和SPI作为壁材制备的SCP-NE微胶囊在胃肠液释放中具有良好的缓释性能。     

聚己内酯载药微球的制备及释药性能研究

首次以利福喷丁为模型药物、聚己内酯为载体材料,制备了用于长效抑制骨结核生长的利福喷丁聚己内酯缓释微球,观察其理化特性和体外释放性能。采用O/W乳化溶剂挥发法制备载利福喷丁聚己内酯微球,系统考察了投药量、聚乙烯醇的浓度、乳化速度对微球形貌、粒径、载药量和包封率的影响。通过对制备工艺的优化,得到最佳制备条件是乳化速度300r·min-1,投药量20mg,聚乙烯醇的浓度2%。所制备的载利福喷丁聚己内酯微球圆整,表面有微孔,大小分布均匀,粒径分布较窄,平均粒径为(27.249±0.256)μm、载药量(3.098±0.011)%、包封率(34.078±0.123)%。实验结果表明:聚己内酯是负载利福喷丁的一种理想控释材料。     

BSA-PLGA微球的优化制备及特性

目的:优化BSA-PLGA微球制备工艺,并对其包封率、形态、体外释放药物及微球包裹前后BSA的稳定性进行评价。方法:以PLGA为载体,采用复乳溶剂挥发法制备BSA-PLGA微球。Micro BCA法测定微球的包封率和载药量,扫描电子显微镜观察微球的形态,激光粒度仪测定粒度及分布,聚丙烯酰胺凝胶电泳(SDS-PAGE)研究微球包裹前后BSA分子结构的完整性,同时考察体外释药性能。结果:根据优化工艺制备的微球外观圆整,平均粒径(2275.8±256.9)nm,包封率(82.59±2.92)%,载药量(13.76±0.49)×10-2%,包裹前后BSA结构稳定,体外释放28天以上,释放曲线符合Higuchi方程。结论:本研究获得了较优化的BSA-PLGA微球制备工艺,所制备的微球具有较高的包封率和明显的缓释效果。     

茶多酚/壳聚糖/海藻酸钠纳米微球的制备

目的探讨各因素对制备茶多酚/壳聚糖/海藻酸钠纳米微球载药率、包埋率的影响,研究纳米微球体外释放行为,为后期缓释抗菌膜的制备提供基础。方法采用单因素实验、正交实验考察海藻酸钠溶液浓度、壳聚糖溶液浓度、CaCl_2溶液浓度、茶多酚溶液浓度对纳米微粒载药率、包封率的影响,并考察其体外释放率。结果当海藻酸钠溶液、壳聚糖溶液、CaCl_2溶液、茶多酚溶液的质量浓度分别为15,10,15,0.8 mg/m L时,该工艺条件下制备的纳米微粒载药率为22.71%,包封率为61.38%,且粒径集中在500 nm左右,有较好的缓释效果。结论所得的最佳工艺制备条件为后期做缓释抗菌膜打下良好基础。     

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.     

葡聚糖中超顺磁氧化铁复合纳米粒子制备影响因素及表征

利用化学共沉积法在改性葡聚糖体系下制备了以超顺磁性纳米氧化铁为核心，外包葡聚糖的壳核结构复合粒子．对制备过程控制因素进行了详细的研究，实验结果表明：利用改性葡聚糖为表面活性剂，碱源快速滴加，合理的控制反应时间，温度可形成小核的超顺磁性纳米氧化铁-葡聚糖复合纳米粒子．在优化的实验条件下，得到核心的平均粒径5nm，总体的平均粒径为7．8nm，并利用XRD、TEM和GLS等手段对其结构，形态和粒径分布进行了表征．     

近红外荧光磁性复合载药脂质体的制备及应用

拟建立以近红外荧光磁性复合脂质体(NFMSLs)为模型药物载体、盐酸多柔比星(DOX)为包封药物的药物输送系统,研究了近红外荧光磁性载药复合脂质体(DOX-NFMSLs)的制备、性质及初步应用.采用共沉淀法制备FeO4磁流体,CdTe掺杂Se制备近红外量子点CdSeTe,薄膜分散法制备DOX-NFMSLs.用DOX荧光分光光度法测定DOX-NFMSLs的包封率和体外药物释放率;用DOX-NFMSLs与HepG2肝癌细胞共孵育来进行细胞成像和细胞毒性实验.结果表明,近红外CdSeTe量子点粒径约为5nm,闪锌矿结构,发射波长824 nm.磷脂与胆固醇质量比为8∶1,药脂比为1∶20的DOX-NFMSLs平均粒径为252.9 nm,Zeta电位为-48.6 mV,理想释放药物温度为41℃,平均包封率为(74.84±0.89)％.DOX-NFMSLs对HepG2肝癌细胞有一定的抗癌效果.得到了具有良好磁响应、释药温度T=41℃、可近红外成像的载药脂质体.     

Chlorogenic acid stabilized nanostructured lipid carriers (NLC) of atorvastatin: formulation,design and in vivo evaluation

The present work was aimed at developing an optimized oral nanostructured lipid carrier (NLC) formulation of poorly soluble atorvastatin Ca (AT Ca) and assessing its in vitro release, oral bioavailability and pharmacodynamic activity. In this study, chlorogenic acid, a novel excipient having synergistic cholesterol lowering activity was utilized and explored in NLC formulation development. The drug-loaded NLC formulations were prepared using a high pressure homogenization technique and optimized by the Box-Behnken statistical design using the Design-Expert software. The optimized NLC formulation was composed of oleic acid and stearic acid as lipid phase (0.9% w/v), poloxamer 188 as surfactant (1% w/v) and chlorogenic acid (0.05% w/v). The mean particle size, polydispersity index (PDI) and % drug entrapment efficiency of optimized NLC were 203.56?±?8.57?nm, 0.27?±?0.028 and 83.66?±?5.69, respectively. In vitro release studies showed that the release of drug from optimized NLC formulations were markedly enhanced as compared to solid lipid nanoparticles (SLN) and drug suspension. The plasma concentration time profile of AT Ca in rats showed 3.08- and 4.89-fold increase in relative bioavailability of developed NLC with respect to marketed preparation (ATORVA® tablet) and drug suspension, respectively. Pharmacodynamic study suggested highly significant (**p?0.01) reduction in the cholesterol and triglyceride values by NLC in comparison with ATORVA® tablet. Therefore, the results of in vivo studies demonstrated promising prospects for successful oral delivery of AT Ca by means of its chlorogenic acid integrated NLC.     

Development and evaluation of nanostructured lipid carriers-based gel of isotretinoin

In the present work attempts have been made to prepare the nanostructured lipid carriers (NLC) gel, by using the poorly water-soluble drug isotretinoin (IT), which is preferably used in the case of acne. The four different formulations of IT-NLC (NLC 1–NLC 4) were prepared using solid and liquid lipid with Tween 80 in different ratios by the hot homogenization method. Properties of entrapment efficiency and drug release behavior were investigated for all formulations from this NLC 4 formulation and optimized. Evaluation of NLC 4 such as particle size, zeta potential, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM), x-ray diffraction (XRD), and photostabilty study was performed. The nanoparticles were suitably gelled and evaluated for drug content, pH, spreadability, extrudability, rheology, and drug release. Safety to gel was assessed using primary skin irritation studies. The formulated NLC 4 was spherical in shape, with average particle size 154.1?nm, zeta potential ?26.9?mV, and entrapment efficiency 91.85%?±?0.10%. The results showed that entrapment of IT into NLCs reduced its photo degradation. IT-NLC gel showed a faster onset of action and elicited prolonged activity. The IT-NLC gel was less irritating, which shows improving ability for skin tolerability and being a carrier for topical delivery.     

Formulation and in vitro evaluation of prolonged release floating microspheres of atenolol using multicompartment dissolution apparatus

The aim of the present work was to prepare floating microspheres of atenolol as prolonged release multiparticulate system and evaluate it using novel multi-compartment dissolution apparatus. Atenolol loaded floating microspheres were prepared by emulsion solvent evaporation method using 3² full factorial design. Formulations F1 to F9 were prepared using two independent variables (polymer ratio and % polyvinyl alcohol) and evaluated for dependent variables (particle size, percentage drug entrapment efficiency and percentage buoyancy). The formulation(F8) with particle size of 329?±?2.69 µm, percentage entrapment efficiency of 61.33% and percentage buoyancy of 96.33% for 12?h was the of optimized formulation (F8). The results of factorial design revealed that the independent variables significantly affected the particle size, percentage drug entrapment efficiency and percentage buoyancy of the microspheres. In vitro drug release study revealed zero order release from F8 (98.33% in 12?h). SEM revealed the hollow cavity and smooth surface of the hollow microspheres.     

Preparation and optimization of doxorubicin-loaded albumin nanoparticles using response surface methodology

Background: The objective of this work was to optimize the preparation of doxorubicin-loaded albumin nanoparticles (Dox-A-Nps) through desolvation procedures using response surface methodology (RSM). A central composite design (CCD) for four factors at five levels was used in this study.

Method: Albumin nanoparticles were prepared through a desolvation method and were optimized in the aid of CCD. Albumin concentration, amount of doxorubicin, pH values, and percentage of glutaraldehyde were selected as independent variables, particle size, zeta potential, drug loading, encapsulation efficiency, and nanoparticles yield were chosen as response variables. RSM and multiple response optimizations utilizing a quadratic polynomial equation were used to obtain an optimal formulation.

Results: The optimal formulation for Dox-A-Nps was composed of albumin concentration of 17?mg/ml, amount of doxorubicin of 2?mg/ml, pH value is 9 and percentage of glutaraldehyde of 125% of the theoretic amount, under which the optimized conditions gave rise to the actual average value of mean particle size (151?±?0.43?nm), zeta potential (?18.8?±?0.21 mV), drug loading efficiency (21.4?±?0.70%), drug entrapment efficiency (76.9?±?0.21%) and nanoparticles yield (82.0?±?0.34%). The storage stability experiments proved that Dox-A-Nps stable in 4°C over the period of 4 months. The in vitro experiments showed a burst release at the initial stage and followed by a prolonged release of Dox from albumin nanoparticles up to 60?h.

Conclusions: This study showed that the RSM-CCD method could efficiently be applied for the modeling of nanoparticles, which laid the foundation of the further research of immuno nanoparticles.     

Development and optimization of locust bean gum and sodium alginate interpenetrating polymeric network of capecitabine

Objective: The objective of the study was to develop interpenetrating polymeric network (IPN) of capecitabine (CAP) using natural polymers locust bean gum (LBG) and sodium alginate (NaAlg).

Significance: The IPN microbeads were optimized by Box–Behnken Design (BBD) to provide anticipated particle size with good drug entrapment efficiency. The comparative dissolution profile of IPN microbeads of CAP with the marketed preparation proved an excellent sustained drug delivery vehicle.

Methods: Ionotropic gelation method utilizing metal ion calcium (Ca²⁺) as a cross-linker was used to prepare IPN microbeads. The optimization study was done by response surface methodology based Box–Behnken Design. The effect of the factors on the responses of optimized batch was exhibited through response surface and contour plots. The optimized batch was analyzed for particle size, % drug entrapment, pharmacokinetic study, in vitro drug release study and further characterized by FTIR, XRD, and SEM. To study the water uptake capacity and hydrodynamic activity of the polymers, swelling studies and viscosity measurement were performed, respectively.

Results: The particle size and % drug entrapment of the optimized batch was 494.37?±?1.4?µm and 81.39?±?2.9%, respectively, closer to the value predicted by Minitab 17 software. The in vitro drug release study showed sustained release of 92% for 12?h and followed anomalous drug release pattern. The derived pharmacokinetic parameters of optimized batch showed improved results than pure CAP.

Conclusion: Thus, the formed IPN microbeads of CAP proved to be an effective extended drug delivery vehicle for the water soluble antineoplastic drug.     

Design and development of bioinspired calcium phosphate nanoparticles of MTX: pharmacodynamic and pharmacokinetic evaluation

The aim of this investigation is the management of rheumatoid arthritis (RA) by developing methotrexate-loaded calcium phosphate nanoparticles (MTX-CAP-NP) and to evaluate pharmacokinetic and pharmacodynamic behavior in adjuvant induced arthritis model. The nanoparticles were synthesized by wet precipitation method and optimized by Box-Behnken experimental design. MTX-CAP-NPs were characterized by TEM, FTIR, DSC and XRD studies. The particle size, zeta potential and entrapment efficiency of the optimized nanoparticles were found to be 204.90?±?64?nm, ?11.58?±?4.80?mV, and 88.33?±?3.74%, respectively. TEM, FTIR, DSC and XRD studies revealed that the developed nanoparticles were nearly spherical in shape and the crystalline structure of CAP-NP was not changed after MTX loading. The pharmacokinetic studies revealed that MTX-CAP-NP enhanced bioavailability of MTX by 2.6-fold when compared to marketed formulation (FOLITRAX-10). Under pharmacodynamic evaluation, arthritic assessment, radiography and histopathology studies revealed that CAP has ability to regenerate cartilage and bone therefore, together with MTX, MTX-CAP-NPs have shown significant reduction in disease progression. The overall work demonstrated that the developed nanodelivery system was well tolerated and more effective than the marketed formulation.     

Hyaluronic acid-coated cationic nanostructured lipid carriers for oral vincristine sulfate delivery

The goal of this research is to structure a hyaluronic acid modified nanostructured lipid carrier (HA-NLCs) for vincristine sulfate (VCR) delivery, and detect its efficiency to improve the oral bioavailability. Emulsion solvent evaporation method was used to prepare the HA-NLCs nanoparticles. The particle size, zeta potential and entrapment efficiency of VCR-NLCs and HA-NLCs were 187?±?3.52?nm, ?8.61?±?1.29?mV, 33.12?±?1.16% and 192?±?4.41?nm, ?32.82?±?2.64?mV, 34.41?±?2.21%, respectively. HA-NLCs could significantly improve the cellular uptake efficiency and cytotoxicity in MCF-7 cells than other VCR formulations. The expressions of apoptosis related protein Caspase-3, Caspase-9, Bax and Bcl-2 were estimated by western blot assay in MCF-7 cells, and HA-NLCs exhibited the strongest effect in promoting cell apoptosis. The pharmacokinetics of HA-NLCs was evaluated in Sprague–Dawley male rats and the relative oral bioavailability of HA-NLCs and VCR-NLCs was improved about 1.8-fold and two-fold compared with VCR solution, respectively. Therefore, these results indicated that HA-NLCs could significantly improve the oral bioavailability and was a promising vehicle for the oral delivery of VCR.     

Cuboidal lipid polymer nanoparticles of rosuvastatin for oral delivery

The present work aimed to develop and characterize sustained release cuboidal lipid polymeric nanoparticles (LPN) of rosuvastatin calcium (ROS) by solvent emulsification-evaporation process. A three factor, two level (2³) full-factorial design was applied to study the effect of independent variables, i.e. amount of lipid, surfactant and polymer on dependent variables, i.e. percent entrapment efficiency and particle size. Optimized formulations were further studied for zeta potential, TEM, in vitro drug release and ex vivo intestinal permeability. Cuboidal nanoparticles exhibited average particle size 61.37?±?3.95?nm, entrapment efficiency 86.77?±?1.27% and zeta potential ?6.72?±?3.25?mV. Nanoparticles were lyophilized to improve physical stability and obtain free-flowing powder. Effect of type and concentration of cryoprotectant required to lyophilize nanoparticles was optimized using freeze-thaw cycles. Mannitol as cryoprotectant in concentration of 5-8% w/v was found to be optimal providing zeta potential ?20.4?±?4.63?mV. Lyophilized nanoparticles were characterized using FTIR, DSC, XRD and SEM. Absence of C=C and C–F aromatic stretch at 1548 and 1197?cm^?1, respectively, in LPN indicated coating of drug by lipid and polymer. In vitro diffusion of ROS using dialysis bag showed pH-independent sustained release of ROS from LPN in comparison to drug suspension. Intestinal permeability by non-everted gut sac model showed prolonged release of ROS from LPN owing to adhesion of polymer to mucus layer. In vivo absorption of ROS from LPN resulted in 3.95-fold increase in AUC_0–last and 7.87-fold increase in mean residence time compared to drug suspension. Furthermore modified tyloxapol-induced rat model demonstrated the potential of ROS-loaded LPN in reducing elevated lipid profile.     

Process,optimization, and characterization of budesonide-loaded nanostructured lipid carriers for the treatment of inflammatory bowel disease

The major challenge involved in the treatment of inflammatory bowel disease is targeted delivery of the drug at the site of inflammation. As nanoparticles possess the ability to accumulate at the site of inflammation, present investigation aims at development of Budesonide-loaded nanostructured lipid carrier systems (BDS-NLCs) for the treatment of inflammatory bowel disease. BDS-NLCs were prepared by employing a high pressure homogenization technique. Various preliminary trials were performed for optimization of the NLCs in which different processes, as well as formulation parameters, were studied. The BDS-NLCs was optimized statistically by applying a 3-factor/3-level Box–Behnken design. Drug concentration, surfactant concentration, and emulsifier concentration were selected as independent variables, and % entrapment efficiency and particle size were selected as dependent variables. The best batch comprises of 10%, 7%, and 20% w/w concentration of drug, surfactant, and emulsifier, respectively, with % entrapment efficiency of 92.66?±?3.42% and particle size of 284.0?±?4.53?nm. Further, in order to achieve effective delivery of nanoparticulate system to colonic region, the developed BDS-NLCs were encapsulated in Eudragit^® S100-coated pellets. The drug release studies of pellets depict intactness of BDS-NLCs during palletization process, with f₂ value of 75.879. The in vitro evaluation of enteric-coated pellets revealed that a coating level of 15% weight gain is needed in order to impart lag time of 5?h (transit time to reach colon). The results of the study demonstrate that the developed BDS-NLCs could be used as a promising tool for the treatment of inflammatory bowel disease.