The Release of NSAIDs Such as Ibuprofen and Diclofenac from Magnetic Nanoparticles Coated with Dextran

Pharmaceutical Chemistry Journal - In this study, iron oxide (Fe3O4) nanoparticles were synthesized using the Massart co-precipitation method followed by surface coating with dextran. Next, coated...     

Erratum to: Thermodynamic Changes Induced by Intermolecular Interaction Between Ibuprofen and Chitosan: Effect on Crystal Habit,Solubility and In Vitro Release Kinetics of Ibuprofen

Pharmaceutical Research -     

酸敏性葡聚糖纳米凝胶的制备与释药性质考察

目的制备具有酸敏特性的聚（甲基丙烯酸缩水甘油酯修饰葡聚糖,dex GMA）/（丙烯酸,AAc）纳米凝胶,研究其降解和释药性质。方法乳液聚合法制备poly(dex GMA/AAc)纳米凝胶,测定不同pH值下的粒度分布,以红霉素（EM）为药物模型,动态透析法测定纳米凝胶在不同pH值下的释药性质。结果poly(dex GMA/AAc)纳米凝胶的平均粒径约为100 nm,包裹率、载药率分别为90.7%和1.06%。在无酶人工胃液 (SGF) 2 h纳米凝胶的药物累积释放率分别为7.0%,之后在无酶人工肠液(SIF)里4 h 内增加到37.0%。结论poly(dex GMA/AAc)纳米凝胶具有酸敏特性,在SGF里释放少量药物,在SIF里凝胶溶胀、降解,药物释放量明显增大。poly(dex GMA/AAc)纳米凝胶是潜在的结肠靶向载体。     

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。     

Doxorubicin Loading,Release, and Stability of Polyamidoamine Dendrimer-Coated Magnetic Nanoparticles

Nanotechnology is a promising alternative to overcome the limitations of classical chemotherapy. As a novel approach, dendrimer-coated magnetic nanoparticles (DcMNPs) maintain suitable drug delivery system because of their buildup of functional groups, symmetry perfection, nanosize, and internal cavities. They can also be targeted to the tumor site in a magnetic field. The aim of this study is to obtain an effective targeted delivery system for doxorubicin, using polyamidoamine (PAMAM) DcMNPs. Different generations (G₂, G₃, G₄, and G₇) of PAMAM DcMNPs were synthesized. Doxorubicin loading, release, and stability efficiencies in these nanoparticles (NPs) were studied. The results showed that low-generation NPs obtained in this study have pH-sensitive drug release characteristics. G₄DcMNP, which releases most of the drug in lower pH, seems to be the most suitable generation for efficient Doxorubicin delivery. Furthermore, application of doxorubicin-loaded G₄DcMNPs may help to overcome doxorubicin resistance in MCF-7 cells. On the contrary, G₂ and G₃DcMNPs would be suitable for the delivery of drugs such as vinca alkaloids (Johnson IS, Armstrong JG, Gorman M, Burnett JP. 1963. Cancer Res 23:1390–1427.) and taxenes (Clarke SJ, Rivory LP. 1999. Clin Pharmacokinet 36(2):99–114.), which show their effects in cytoplasm. The results of this study can provide new insights in the development of pH-sensitive targeted drug delivery systems to overcome drug resistance during cancer therapy.     

胰岛素壳聚糖胶态纳米粒的制备及体外释药性能

采用离子趋向凝胶化法制备了胰岛素壳聚糖胶态微粒,并考察了外观、粒径和体外释药性能.所得产品呈球形,表面光滑圆整,平均粒径为276nm,多分散系数为0.08.体外释药呈pH依赖性,释药速度受载药量及泊洛沙姆188含量的影响.     

Design and Evaluation of Ethyl Cellulose Based Matrix Tablets of Ibuprofen with pH Modulated Release Kinetics

Controlled release preparations have been reported to reduce the gastro irritant and ulcerogenic effects of non steroidal antiinflammatory drugs. In the present study, an attempt was made to develop matrix tablet-based controlled release formulations of ibuprofen, using ethyl cellulose as the rate-controlling polymer. In order to prevent initial release of the drug in the acidic environment of the stomach, cellulose acetate phthalate was incorporated in the matrix in varying amounts. It was found that with increasing the proportion of ethyl cellulose in the matrix, the drug release was extended for 14-16 h. Incorporation of cellulose acetate phthalate in ethyl cellulose matrix provided very low initial release of the drug in the first 2-3 h followed by enhanced release rate in alkaline medium owing to the high solubility of cellulose acetate phthalate at basic pH which led to creation of a porous matrix. It was concluded that combination of cellulose acetate phthalate with ethyl cellulose in the matrix base can be an effective means of developing a controlled release formulation of ibuprofen with very low initial release followed with controlled release up to 14-16 h.     

Chitosan Nanoparticles for Plasmid DNA Delivery: Effect of Chitosan Molecular Structure on Formulation and Release Characteristics

Chitosan can be useful as a nonviral vector for gene delivery. Although there are several reports to form chitosan-pDNA particles, the optimization and effect on transfection remain insufficient. The chitosan-pDNA nanoparticles were formulated using complex coacervation and solvent evaporation techniques. The important parameters for the encapsulation efficiency were investigated, including molecular weight and deacetylation degree of chitosan. We found that encapsulation efficiency of pDNA is directly proportional with deacetylation degree, but there is an inverse proportion with molecular weight of chitosan. DNA-nanoparticles in the size range of 450–820 nm depend on the formulation process. The surface charge of the nanoparticles prepared with complex coacervation method was slightly positive with a zeta potential of +9 to +18 mV; nevertheless, nanoparticles prepared with solvent evaporation method had a zeta potential ～ +30 mV. The pDNA-chitosan nanoparticles prepared by using high deacetylation degree chitosan having 92.7%, 98.0%, and 90.4% encapsulation efficiency protect the encapsulated pDNA from nuclease degradation as shown by electrophoretic mobility analysis. The release of pDNA from the formulation prepared by complex coacervation was completed in 24 hr whereas the formulation prepared by evaporation tecnique released pDNA in 96 hr, but these release profiles are not statistically significant compared with formulations with similar structure p >. 05). According to the results, we suggest nanoparticles have the potential to be used as a transfer vector in further studies.     

Controlled Drug Release of Smart Magnetic Self-Assembled Micelle,Kinetics and Transport Mechanisms

Magnetic nanocarriers have been extensively used as a potential drug release system for breast cancer therapy. This work investigates drug release kinetics and transport mechanisms of dasatinib (DAS) anticancer drugs encapsulated in nanomagnetic self-assembled micelles. The drug release kinetics of DAS from the nanomagnetic micelles (NMM) was predicted by fitting the drug release experimental data to four different empirical models at pH values 7.4 and 5. Moreover, a simple mathematical model that can predict the drug release from bulk eroding polymer matrices has been developed using the COMSOL Multiphysics® program. The diffusional egress of the DAS release through the NMM was carried out by evaluating the diffusion coefficients inside NMM using Fick's second law and diffusion coefficients in the solution utilizing the Stokes-Einstein equation. The results revealed that NMM exhibited a superior sustained drug release rate in acidic conditions compared to the neutral state. The Peppas-Sahlin and COMSOL models gave the best fitting for the experimental drug release data and eroding matrices obtained from free DAS, DAS-micelles, and DAS-magnetic micelles at both pH values with correlation coefficients reached to 0.99. The transport mechanisms results showed a Fickian diffusion mechanism controlled with the highest diffusion coefficients of NMM in acidic conditions, while a significant relaxation contribution was observed at the neutral state.     

Preparation and In Vitro and In Vivo Evaluation Of Panax Notoginseng Saponins-loaded Nanoparticles Coated with Trimethyl Chitosan Derivatives

In this study, novel Panax notoginseng saponins (PNS)-loaded nanoparticles coated with the Trimethyl chitosan (TMC) derivatives TMC-VB₁₂ and TMC-Cys (PPTT-NPs) were developed to improve the oral absorption of the constituents. PPTT-NPs were prepared by the double emulsion method and showed different encapsulation effects on the major components, including Rg1, Rb1, and R1, in PNS. In vivo, the absorption rate constant and apparent absorption coefficient of PPTT-NPs were higher than PNS solution. These findings preliminarily proved that PPTT-NPs can promote intestinal absorption to a certain extent. The pharmacokinetic results indicated that the blood concentration and the area under the curve of Rg1 and Rb1 in the PPTT-NPs were higher than Xueshuantong capsules. The cell viability of PPTT-NPs was above 90% within 25-150 μg/mL. PPTT-NPs promoted the cellular uptake of PNS by receptor-mediated endocytosis. In summary, NPs coated with TMC-VB₁₂ and TMC-Cys can be used as promising drug delivery systems.     

Chitosan Film Containing Poly(D,L-Lactic-Co-Glycolic Acid) Nanoparticles: A Platform for Localized Dual-Drug Release

Purpose  

To characterize and evaluate chitosan film containing PLGA nanoparticles (NPs) as a platform for localized dual-drug release.     

布洛芬缓释片的生产及体外释药性能研究

目的:研究布洛芬骨架缓释片从研试处方到生产处方的放大过程中,工艺参数对药物释放性能的影响.方法:通过测定不同时间点药物累积释药量,考察布洛芬缓释片的释药机制;并考察了致孔剂、制粒工艺和压片设备等因素对药物释放的影响,还对骨架片进行了6个月的加速试验.结果:布洛芬不溶性骨架缓释片的药物释放规律符合Higuchi方程;致孔剂羟丙甲纤维素(HPMC)的加入可以提高药物释放速率;不同制粒工艺和压片设备对药物释放的均匀性有一定影响;在一定压力范围内,药物释放对压力敏感.结论:布络芬缓释片的大生产中,制粒工艺、致孔剂用量和压片设备对药物释放有影响,可以通过优化上述工艺参数来提高产品质量.     

壳聚糖包覆脂质体递药系统的研究进展

脂质体在药物传递方面被广泛研究,但因结构稳定性差等因素使其应用受到了限制.壳聚糖是一种阳离子多糖,具有良好的生物相容性、生物降解性以及生物黏附性,并且可经化学改性成为性能更佳的壳聚糖衍生物.近年来,壳聚糖及其衍生物包覆脂质体在载药方面的研究得到了越来越多学者的关注.壳聚糖或其衍生物修饰脂质体,可提高其稳定性、黏附渗透性...     

Preparation,Characterization and Protein Loading of Hexanoyl-Modified Chitosan Nanoparticles

Hexanoyl chitosan was synthesized through a coupling reaction between chitosan and hexanoic anhydride. Proton nuclear magnetic resonance (¹HNMR) and fourier-transform infrared (FTIR) spectroscopy studies showed the formation of hexanoyl chitosan. The nanoparticles of hexanoyl chitosan were prepared through ionotropic gelation with tripolyphosphate (TPP) followed by sonication. The hexanoyl chitosan-TPP nanoparticles exhibited uniform spherical shape with smooth surface as observed by atomic force microscopy and transmission electron microscopy. The particle size of nanoparticles was between 54.1 to 724 nm with a mean diameter of 324 nm. At 0.2, 0.4, and 0.6 mg/mL bovine serum albumin initial concentration, the encapsulation efficiency and loading capacity of hexanoyl-chitosan-TPP nanoparticles were 58.2, 44.5, and 28.1%, and 14.1, 23.4, and 30.3%, respectively.     

叶酸偶联壳聚糖纳米粒的制备

目的制备叶酸偶联的壳聚糖纳米粒。方法根据叶酸与壳聚糖的偶联比选择最佳工艺条件,通过叶酸活性酯与壳聚糖上的氨基反应,制得叶酸偶联的壳聚糖,再通过离子交联法制得叶酸偶联壳聚糖纳米粒,并测定纳米粒的粒径和表面电位。结果正交实验结果显示叶酸活性酯用量和反应温度是影响偶联比的主要因素,在叶酸活性酯与壳聚糖用量比为2∶1,反应温度50℃,反应时间2 h的条件下可得到偶联比大致为每个壳聚糖分子上偶联3个叶酸分子的叶酸偶联壳聚糖。所制得的纳米粒粒径316 nm,表面电位为(24.85±1.14)mV,透射电镜下观察其形态圆整。结论该方法可成功制备叶酸偶联壳聚糖纳米粒。     

Effects of Organic Acids on Drug Release From Ternary Polypeptide Nanoparticles Entrapping Carfilzomib

Carfilzomib (CFZ) is an FDA-approved proteasome inhibitor with antineoplastic properties against various cancers, yet its short blood retention time after intravenous injection (< 30 min) makes clinical applications limited to multiple myeloma. We previously developed ternary polypeptide nanoparticles (tPNPs) as a new nanoparticle formulation of CFZ to overcome these limitations. The formulation was prepared by polyion complexation between poly(ethylene glycol)-poly(L-glutamate) block copolymers (PEG-PLE) and CFZ-cyclodextrin (CD) inclusion complexes, where CDs were positively charged with 7 primary amines attached while PEG-PLE carried 100 carboxyl groups per polymer chain. Although tPNPs greatly improved biostability of CFZ, CFZ-loaded tPNPs (CFZ-tPNPs) still showed burst drug release and mediocre drug retention under physiological conditions. To address these issues, organic acids are tested as stabilizers in this study to improve particle stability and drug retention for tPNPs. Charge densities in the core of CFZ-tPNPs were optimized with selected organic acids such as citric acid (CA) and lactic acid (LA) at varying mixing ratios. Organic acids successfully maintained small particle size suitable for intravenous injection and drug delivery (diameters < 60 nm), improved CFZ solubility (> 1 mg/mL), allowed for lyophilization and easy reconstitution in various buffers, enhanced drug retention (> 60% post 24 h incubation), and suppressed burst drug release in the first 6 h following solubilization. These results demonstrate that organic acid stabilized tPNPs are useful as an injection formulation of CFZ, which may expand the utility of the proteasome inhibitor.