Single-phased luminescent mesoporous nanoparticles for simultaneous cell imaging and anticancer drug delivery

Multifunctional materials for biological use have mostly been designed with composite or hybrid nanostructures in which two or more components are incorporated. The present work reports on a multifunctional biomaterial based on single-phased luminescent mesoporous lanthanide oxide nanoparticles that combine simultaneous drug delivery and cell imaging. A simple strategy based on solid-state-chemistry thermal decomposition process was employed to fabricate the spherical mesoporous Gd(2)O(3):Eu nanoparticles with homogeneous size distribution. The porous nanoparticles developed by this strategy possess well-defined mesopores, large pore size and volume, and high specific surface area. The mesoporous features of nanoparticles impart the material with capabilities of loading and releasing the drug with a relatively high loading efficiency and a sustained release behavior of drugs. The DOX-loaded porous Gd(2)O(3) nanoparticles are able to kill the cancer cells efficiently upon incubation with the human cervical carcinoma (HeLa) cells, indicating the potential for treatment of cancer cells. Meanwhile, the intrinsic luminescence of Gd(2)O(3):Eu nanoparticles gives the function of optical imaging. Therefore, the drug release activity and effect of drugs on the cells can be effectively monitored via luminescence of nanoparticles themselves, realizing multifunctionality of simultaneous cell imaging and anticancer drug delivery in a single-phased nanoparticle.     

Non-viral DNA delivery from porous hyaluronic acid hydrogels in mice

The lack of vascularization within tissue-engineered constructs remains the primary cause of construct failure following implantation. Porous constructs have been successful in allowing for vessel infiltration without requiring extensive matrix degradation. We hypothesized that the rate and maturity of infiltrating vessels could be enhanced by complementing the open pore structure with the added delivery of DNA encoding for angiogenic growth factors. Both 100 and 60 μm porous and non-porous hyaluronic acid hydrogels loaded with pro-angiogenic (pVEGF) or reporter (pGFPluc) plasmid nanoparticles were used to study the effects of pore size and DNA delivery on angiogenesis in a mouse subcutaneous implant model. GFP-expressing transfected cells were found inside all control hydrogels over the course of the study, although transfection levels peaked by week 3 for 100 and 60 μm porous hydrogels. Transfection in non-porous hydrogels continued to increase over time corresponding with continued surface degradation. pVEGF transfection levels were not high enough to enhance angiogenesis by increasing vessel density, maturity, or size, although by 6 weeks for all pore size hydrogels more hydrogel implants were positive for vascularization when pVEGF polyplexes were incorporated compared to control hydrogels. Pore size was found to be the dominant factor in determining the angiogenic response with 60 μm porous hydrogels having more vessels/area present than 100 μm porous hydrogels at the initial onset of angiogenesis at 3 weeks. The results of this study show promise for the use of polyplex loaded porous hydrogels to transfect infiltrating cells in vivo and guide tissue regeneration and repair.     

In vitro degradation of porous poly(L-lactic acid) foams

This study investigated the in vitro degradation of porous poly(L-lactic acid) (PLLA) foams during a 46-week period in pH 7.4 phosphate-buffered saline at 37 degrees C. Four types of PLLA foams were fabricated using a solvent-casting, particulate-leaching technique. The three types had initial salt weight fraction of 70, 80, and 90%, and a salt particle size of 106-150 microm, while the fourth type had 90% initial weight fraction of salt in the size range 0-53 microm. The porosities of the resulting foams were 0.67, 0.79, 0.91, and 0.84, respectively. The corresponding median pore diameters were 33, 52, 91, and 34 microm. The macroscopic degradation of PLLA foams was independent of pore morphology with insignificant variation in foam weight, thickness, pore distribution, compressive creep behavior, and morphology during degradation. However, decrease in melting temperature and slight increase in crystallinity were observed at the end of degradation. The foam half-lives based on the weight average molecular weight were 11.6+/-0.7 (70%, 106-150 microm), 15.8+/-1.2 (80%, 106-150 microm), 21.5+/-1.5 (90%, 106-150 microm), and 43.0+/-2.7 (90%, 0-53 microm) weeks. The thicker pore walls of foams prepared with 70 or 80% salt weight fraction as compared to those with 90% salt weight fraction contributed to an autocatalytic effect resulting in faster foam degradation. Also, the increased pore surface/volume ratio of foams prepared with salt in the range 0-53 microm enhanced the release of degradation products thus diminishing the autocatalytic effect and resulting in slower foam degradation compared to those with salt in the range 106-150 microm. Formation and release of crystalline PLLA particulates occurred for foams fabricated with 90% salt weight fraction at early stages of degradation. These results suggest that the degradation rate of porous foams can be engineered by varying the pore wall thickness and pore surface/volume ratio.     

Preparation and degradation behavior of polyanhydrides nanoparticles

Polyanhydrides have been used in many drug delivery systems because of their biodegradability and biocompatibility. Their degradation pattern of surface erosion made them suitable for stable drug release applications. However, in nanoparticle systems, this degradation pattern may not hold, and the drug release kinetics will be different also. In this study, copolymers of 1,3-bis(p-carboxyphenoxy)propane (CPP) and sebacic acid (SA) were synthesized to investigate the different degradation patterns of disk and nanoparticle forms of polyanhydride, in addition to the study of the method of preparation of nanoparticles from these copolymers. By using oil-in-water emulsion and poly(vinyl alcohol) (PVA) as emulsifier, nanoparticles of the size 200-500 nm were prepared. The size of the particles can be controlled by varying polymer concentration or PVA concentration, but different SA:CPP ratio did not affect the particle size significantly. Degradation was followed by detecting the amount of monomers released to the medium. It was found that CPP and SA were released at approximately the same rate from nanoparticles; while in disk form, SA was released much faster than CPP. It was found that contrary to general trend in disks, higher CPP content, a more hydrophobic component than SA, in the copolymer actually accelerated the degradation of nanoparticles.     

Mathematical modeling of drug release from nanostructured porous Si: Combining carrier erosion and hindered drug diffusion for predicting release kinetics

A novel, empirical, macroscopic model is developed to describe the release of a model anticancer drug, Mitoxantrone, from native and chemically modified porous Si (PSi) thin films. Drug release from these carriers results from a combination of two mechanisms, i.e. out-diffusion of the drug molecules and erosion of the Si scaffold. Thus, the proposed mathematical model adapts the Crank model to lump the effects of temporal changes in molecular interactions and carrier scaffold erosion into a comprehensive model of hindered drug diffusion from nanoscale porous systems. Careful characterization of pore size, porosity, surface area, drug loading, as well as Si scaffold degradation profiles, measured over the same time-scale as drug release, are incorporated into the model parameter estimation. A comparison of the experimental and model results shows accurate representation of the data, emphasizing the reliability of the model. The proposed model shows that drug diffusivity values significantly vary with time for the two studied carriers, which are ascribed to the distinctive role of the prevailing physical mechanisms in each system. Finally, secondary validation of the proposed model is demonstrated by showing adequate fit to published data of the release of dexamethasone from similar mesoporous Si carriers.     

Sphere梯度孔结构力学性能有限元分析

建立不同孔径分布的钛合金梯度多孔结构的三维有限元模型,对力学性能进行分析。使用Rhino 5.0和ABAQUS 6.1软件,分别建立sphere、sphere_line、sphere_plane、sphere_point等4种按不同梯度分布的多孔结构有限元模型。对模型分别加载200、400、600、800、1000 N的力,加载力作用于上表面,方向垂直于表面向下,选定下表面为固定约束,计算等效应力及最大主应力。在加载力相同的情况下,sphere_plane梯度孔模型的最大主应力及最大等效应力最大;其次为sphere_point梯度孔模型,较sphere_plane梯度孔模型小42.49%和23.61%;sphere_line梯度孔模型再次之,较sphere_plane梯度孔模型小47.60%和33.12%;sphere无梯度孔模型的最大主应力及最大等效应力最小,较sphere_plane梯度孔模型小68.44%和54.13%。在4种不同梯度孔径分布的多孔结构中,sphere无梯度孔结构的实际受力最小、承载能力最好,其次是sphere_line梯度孔结构,再次是sphere_point梯度孔结构次之,sphere_plane梯度孔结构实际受力最大,其承载能力相比前3种要差。最后通过快速原型对设计出的4种模型进行制备,得到多孔钛合金实体,并对实体进行力学性能测试实验,得出的结论可验证数值模拟分析结果的可靠性。该研究结果可为多孔钛合金植入体设计以及临床应用提供相关设计参考和理论依据。     

Poly(L-lactide)-b-poly(ethylene oxide) copolymers with different arms: hydrophilicity, biodegradable nanoparticles, in vitro degradation, and drug-release behavior

Biodegradable and amphiphilic poly(L-lactide)-b-poly(ethylene oxide) copolymers with different arms (PLLA-b-PEO having one, two, four, and six arms) were successfully synthesized via a two-step synthetic strategy. The hydrophilicity-hydrophobicity balance of these copolymers was mainly controlled by both the arm number of copolymers (i.e., macromolecular architecture) and the poly(ethylene oxide) (PEO) composition. Biodegradable nanoparticles could be generated by direct injection of these PLLA-b-PEO copolymers solutions into distilled water, and their critical micelles concentrations decreased with the increasing arm number of copolymers. Moreover, both the hydrophilic PEO composition and the arm number of copolymers controlled the average size of PLLA-b-PEO nanoparticles, and the nanoparticles with adjustable sizes (20-85 nm) completely meet the size prerequisite (less than 100 nm) for targeted drug delivery. In vitro degradation of PLLA-b-PEO nanoparticles showed that the PLLA composition gradually increased over the degradation time, and the degree of crystallinity of PLLA block within copolymers increased simultaneously. Furthermore, the nimodipine drug loading efficiency of the PLLA-b-PEO copolymers was apparently higher than that of PLLA homopolymers. The drug-release experiments demonstrated that these biodegradable nanoparticles might be used for a short-time controlled release system. Consequently, this will provide a facile method not only to design new PLLA-based biomaterials from both the macromolecular architecture and the hydrophilicity-hydrophobicity balance, but also to fabricate biodegradable nanoparticles with adjustable sizes for drug delivery.     

Inhibition of hypoxia-induced proliferation of pulmonary arterial smooth muscle cells by a mTOR siRNA-loaded cyclodextrin nanovector

The proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a key pathophysiological component of vascular remodeling in pulmonary arterial hypertension (PAH), an intractable disease, for which pharmacotherapy is limited and only slight improvement in survival outcomes have achieved over the past few decades. RNA interference provides a highly promising strategy to the treatment of this chronic lung disease, while efficient delivery of small interfering RNA (siRNA) remains a key challenge for the development of clinically acceptable siRNA therapeutics. With the aim to construct useful nanomedicines, the mammalian target of rapamycin (mTOR) siRNA was loaded into hybrid nanoparticles based on low molecular weight (Mw) polyethylenimine (PEI) and a pH-responsive cyclodextrin material (Ac-aCD) or poly(lactic-co-glycolic acid) (PLGA). This hybrid nanoplatform gave rise to desirable siRNA loading, and the payload release could be modulated by the hydrolysis characteristics of carrier materials. Fluorescence observation and flow cytometry quantification suggested that both Ac-aCD and PLGA nanovectors (NVs) may enter PASMCs under either normoxia or hypoxia conditions as well as in the presence of serum, with uptake and transfection efficiency significantly higher than those of cationic vectors such as PEI with Mw of 25 kDa (PEI25k) and Lipofectamine 2000 (Lipo 2k). Hybrid Ac-aCD or PLGA NV containing siRNA remarkably inhibited proliferation and activated apoptosis of hypoxic PASMCs, largely resulting from effective suppression of mTOR signaling as evidenced by significantly lowered expression of mTOR mRNA and phosphorylated protein. Moreover, these hybrid nanomedicines were more effective than commonly used cationic vectors like PEI25k and Lipo 2k, with respect to cell growth inhibition, apoptosis activation, and expression attenuation of mTOR mRNA and protein. Therefore, mTOR siRNA nanomedicines based on hybrid Ac-aCD or PLGA NV may be promising therapeutics for diseases related to hypoxic abnormal growth of PASMCs.     

5-氟尿嘧啶载自组装水凝胶纳米粒的制备及体外释放

本实验以乙酰化普鲁兰(PA)为基质材料,采用透析法制备新型自组装水凝胶纳米粒,用以增强5-氟尿嘧啶的药物靶向性及药物选择活性,从而达到降低其毒副作用的目的。用傅立叶红外光谱仪(FT-IR)、动态光散射仪(DLS)和场发射扫描电镜(FE-SEM)对其进行表征。分别测量不同浓度、温度以及储存时间下,PA纳米粒的粒径的变化情况,以研究环境因素的改变对PA纳米粒的粒径及其粒径分布的稳定性影响。使用透析方将5-氟尿嘧啶(5-FU)物理包封于自组装纳米粒中,并模拟人体环境进行了体外释放研究。结果表明,PA纳米粒在不同环境条件下,粒径基本保持恒定,具有良好的稳定性;PA纳米粒的粒径在100nm左右,具有良好的表面球形度且分布均匀;不同环境条件变化下,粒径基本保持恒定,具有良好的稳定性;在18h内,5-FU释放量达70%左右,具有明显的缓释作用。乙酰化程度越低,5-FU的缓释效果越好,但载药量略有下降。PA纳米粒是非常具有应用前景的新型5-FU药物载体。     

Paclitaxel-loaded composite fibers: microstructure and emulsion stability

New core/shell fiber structures loaded with paclitaxel were developed and studied. These composite fibers are ideal for forming thin, delicate, biomedically important structures for various applications. Possible applications include fiber-based endovascular stents that mechanically support blood vessels while delivering drugs for preventing restenosis directly to the blood vessel wall, or drug delivery systems for cancer treatment. The core/shell fiber structures were formed by "coating" nylon fibers with porous paclitaxel-containing poly(DL-lactic-co-glycolic acid) structures. Shell preparation ("coating") was performed by freeze-drying water in oil emulsions. The present study focused on the effects of the emulsion's formulation (composition) and processing conditions on the porous shell structure, which actually reflects the emulsion's stability and also the drug release profile from the fibers. In general, extremely porous "shell" structures were obtained with good adhesion to the core fiber. An increase in the emulsion's drug content and copolymer composition demonstrated a significant effect on pore size and distribution, because of enhanced emulsion instability, whereas the homogenization rate and duration had only a slight effect on the pores' microstructure. The thermodynamic parameters in the studied system are thus more important than the kinetic parameters in determining the emulsion's stability and the shell's porous structure.     

盐酸表阿霉素纳米靶向制剂的缓释效应

背景：盐酸表阿霉素是一种广谱抗生素,目前临床使用的不足多为药物释放快、目标组织药物浓度低,静脉给药后广泛分布于体内各种组织器官,不良反应明显。 目的：针对盐酸表阿霉素临床应用的不足,制备盐酸表阿霉素纳米靶向注射制剂。 方法：以叶酸偶联牛血清白蛋白为载体,采用乳化-高压匀质法,制备盐酸表阿霉素纳米靶向注射制剂,以激光粒度分析仪测定纳米颗粒的粒径大小、粒径分布及Zeta电位,扫描电镜观察纳米颗粒的表面形态,高效液相色谱法分析白蛋白负载盐酸表阿霉素纳米制剂的包封率、载药量和释药性能。 结果与结论：制备的盐酸表阿霉素纳米粒外观呈均匀球型,粒径分布较窄,平均粒径为(157.73±     0.40) nm,平均 Zeta 电位为(-30.85±0.43) mV,载药量 22.78%,包封率可达96.24%。体外模拟释药结果表明药物释放曲线分为两个阶段,突释阶段微球释药量在24 h内达42.6%,缓释阶段纳米粒释药持续时间长,在112 h 时释药量达 84.1%,载药纳米粒的药物释放速率持续稳定。结果表明乳化结合高压匀质法制备的盐酸表阿霉素纳米靶向制剂粒径均匀,粒径范围分布窄,载药量和包封率高,具有一定的缓释作用。     

转化生长因子β1基因缓释的壳聚糖纳米粒制备及体外检测***☆

背景：壳聚糖作为一种非病毒载体,具有低毒性、低免疫原性、良好的生物相容性以及带可高正电荷密度的特性,易与带负电荷的DNA通过静电作用形成相互作用体避免核酸酶的降解。 目的：构建负载重组人转化生长因子β1基因的壳聚糖纳米粒,检测其体外缓释转化生长因子β1基因及对软骨细胞基因转染等性能。 方法：将壳聚糖与负载增强型绿色荧光蛋白基因和转化生长因子β1基因的质粒DNA(pDNA)以复凝聚法制成壳聚糖/ pEGFP-TGF-β1纳米粒。 结果与结论：制备的壳聚糖/pEGFP-TGF-β1纳米粒呈球形,粒径、表面电位与pH值相关,随着pH值升高,粒径增大,表面电位减少。纳米粒可有效保护pDNA免受核酸酶的降解。纳米粒的pDNA包封率为(87.5±2.3)%;pDNA可从纳米粒中缓慢释放。体外转染实验证实壳聚糖/pEGFP-TGF-β1纳米粒能转染软骨细胞并在细胞内表达绿色荧光蛋白。提示壳聚糖/ pEGFP-TGF-β1纳米粒能有效保护pDNA免受核酸酶降解,具有良好的缓释转化生长因子β1基因的能力,并能介导基因转染软骨细胞。 关键词：转化生长因子β1;壳聚糖;软骨细胞;组织工程;基因载体 doi:10.3969/j.issn.1673-8225.2012.12.007     

Controlled preparation and properties of porous poly(L-lactide) obtained from a co-continuous blend of two biodegradable polymers

This study prepares porous PLLA from a blend of two biodegradable polymers. This approach is based on a detailed and quantitative morphology control of the blends. Co-continuous blends comprised of poly(L-lactide)/poly(epsilon-caprolactone) PLLA/PCL, were prepared via melt processing. Through a judicious combination of concentration control and a subsequent annealing step it is possible to generate a wide range of sizes for the co-continuous phases. Subsequent extraction of the PCL porogen phase generates a fully interconnected porous PLLA material with a void volume between 50% and 60%. The volume average pore diameter is controlled from 1.5 to 88 microm as measured by mercury intrusion porosimetry. Through static annealing it is also possible to generate porous structures well beyond that upper limit of pore size. The upper limit of pore size reported above is in the range required for scaffolds for tissue engineering. Micrographs of porous polyglycolide and PCL derived from co-continuous blends of PLLA/polyglycolide and PCL/poly(ethylene oxide) are also shown and demonstrate the versatility and wide applicability of this preparation protocol. The porous structures produced from PLLA/PCL blends possess a high level of mechanical integrity and a degree of crystallinity between 25% and 38%. High values of both compressive modulus and strength at 10%-strain are obtained, greater than 190 and 11 MPa, respectively. The compressive modulus is found to be from 10% to 20% of that of the pure PLLA material. A series of loading studies were also carried out and it was shown that under a pressure of 40 atm applied for 1 h, the pores of a 1.5 microm porous PLLA structure were filled to approximately 80% by water. In addition, the loading of an aqueous solution of a model drug compound, bovine serum albumin (BSA), was carried out at 40 atm and the results indicate that large quantities of BSA (up to 25% of the weight of the original porous capsule) can be driven into the pores. These results indicate that the internal porous structure is accessible to aqueous solution and that this material also has potential as a substrate for controlled release applications.     

Chitosan-based nanoparticles as a sustained protein release carrier for tissue engineering applications

Chitosan/tripolyphosphate/chondroitin sulfate (Chi/TPP/CS) nanoparticles were prepared by an ionic gelation method to obtain a controlled release of proteins. Using Nel-like molecule-1 (Nell-1), a novel osteogenic protein, as a model protein, it was demonstrated that adjusting the composition of the particles modulated the protein association and release kinetics of incorporated proteins. Increasing the amounts of Chi crosslinking agents, TPP and CS, in the particles achieved sustained protein release. An increase in crosslinking density decreased degradation rates of the particles. Furthermore, the bioactivity of the protein was preserved during the encapsulating procedure into the particles. To demonstrate the feasibility of Chi/TPP/CS nanoparticles as sustained release carriers for tissue engineering scaffold applications, protein-loaded nanoparticles were successfully incorporated into collagen hydrogels or prefabricated porous poly(lactide-co-glycolide) (PLGA) scaffolds without obstructing the integrity of the hydrogels or porous structure of the scaffolds. Thus, we expect that these particles have a potential for efficient protein carriers in tissue engineering applications, and will be further evaluated in vivo.     

左旋多巴和姜黄素共递送protocells纳米粒的制备及体外评价

目的制备共载左旋多巴和姜黄素protocells纳米粒并进行体外评价。方法以介孔二氧化硅为内核,脂质双分子层为外膜,制备共载左旋多巴和姜黄素protocells纳米粒。使用激光粒度分析仪和透射电子显微镜对所制备纳米粒的形貌、粒径、多分散系数(PDI)和Zeta电势进行表征;采用高效液相色谱法对所制备纳米粒的载药量和包封率进行测定;采用透析袋法对所制备纳米粒的体外释放特性进行考察;应用粒径、Zeta电势、载药量等指标对所制备纳米粒的室温贮存稳定性进行评价。结果制备的载左旋多巴和姜黄素protocells纳米粒粒径分布均一性好、粒子表面呈电负性、平均粒径为(210.9±2.8)nm、PDI为(0.201±0.011)。其中左旋多巴的载药量为(20.28±0.43)%、包封率为(10.14±0.22)%;姜黄素的载药量为(1.97±0.01)%、包封率为(98.32±0.01)%。体外释放结果表明该纳米粒48 h姜黄素累计释放率为59.2%,且可有效阻止左旋多巴的泄漏,降低其在循环系统中的暴露量。稳定性结果表明左旋多巴和姜黄素在protocells纳米粒中稳定性良好。结论载左旋多巴和姜黄素的protocells纳米粒制备工艺简单,具有良好的理化性质、稳定性及所预期的释放性能。     

Design and characterization of microporous hyaluronic acid hydrogels for in vitro gene transfer to mMSCs

The effective and sustained delivery of DNA locally could increase the applicability of gene therapy in tissue regeneration and therapeutic angiogenesis. One promising approach is to use porous hydrogel scaffolds to encapsulate and deliver nucleotides in the form of nanoparticles to the affected sites. We have designed and characterized microporous (μ-pore) hyaluronic acid hydrogels which allow for effective cell seeding in vitro post-scaffold fabrication and allow for cell spreading and proliferation without requiring high levels of degradation. These factors, coupled with high loading efficiency of DNA polyplexes using a previously developed caged nanoparticle encapsulation (CnE) technique, then allowed for long-term sustained transfection and transgene expression of incorporated mMSCs. In this study, we examined the effect of pore size on gene transfer efficiency and the kinetics of transgene expression. For all investigated pore sizes (30, 60, and 100 μm), encapsulated DNA polyplexes were released steadily, starting by day 4 for up to 10 days. Likewise, transgene expression was sustained over this period, although significant differences between different pore sizes were not observed. Cell viability was also shown to remain high over time, even in the presence of high concentrations of DNA polyplexes. The knowledge acquired through this in vitro model can be utilized to design and better predict scaffold-mediated gene delivery for local gene therapy in an in vivo model where host cells infiltrate the scaffold over time.     

Alginate-folic acid-modified chitosan nanoparticles for photodynamic detection of intestinal neoplasms

Colorectal cancer is one of the leading causes of cancer death and often goes undetected with current colonoscopy practices. Improved methods of detecting dysplasia and tumors during colonoscopy could significantly improve mortality. Herein, we report a high-performance nanoparticle for photodynamic detection of colorectal cancer, where alginate is physically complexed with folic acid-modified chitosan to form nanoparticles with improved drug release in the cellular lysosome. The incorporated alginate molecules could complex stably with chitosan via electrostatic attraction, and the z-average diameter and zeta-potential of the prepared nanoparticles (fCAN) was 115 nm and 22 mV, respectively, enough to keep the nanoparticles stable in aqueous suspension without aggregation. When loaded with 5-aminolevulinic acid (5-ALA; 27% loading efficiency), the nanoparticles (fCANA) displayed no differences in particle size or zeta-potential compared to fCAN. Moreover, the fCANA nanoparticles were readily taken up by colorectal cancer cells via folate receptor-mediated endocytosis. Subsequently, the loaded 5-ALA was release in the lysosome, and this was promoted by the reduced attraction intensity between chitosan and 5-ALA via the deprotonated alginate, resulting in a higher intracellular PpIX accumulation for the photodynamic detection. These studies demonstrate that the alginate incorporated and folic acid-conjugated chitosan nanoparticles are excellent vectors for colorectal-specific delivery of 5-ALA for fluorescent endoscopic detection.     

Novel carboxymethylcellulose-based microporous hydrogels suitable for drug delivery

Several materials capable of acting as structures for controlled release were analysed for the fabrication of matrices. Among those used, hydrophilic polysaccharides appeared to be the most suitable materials. Carboxymethylcellulose (a semi-synthetic polysaccharide) was chemically cross-linked with a 60% and 90% cross-linking degree in order to obtain hydrogels and utilised as matrix for the realisation of controlled drug release systems. The morphology of the gels was changed in order to obtain a microporous structure with different porosity (14, 30 and 40 μm). The obtained porous matrices were characterised in terms of pore density, dimension and swelling behaviour. The influence of both the pore dimension and technique of loading on the release kinetics was analysed. By increasing the pore dimension the release of ibuprofen-lysin was slower. Inducing the microporous structure after the loading of the hydrogel with the drug resulted in a slower release.     

Layer-by-layer self-assembly vectors for gene delivery

The success of gene therapy largely relies on the development of high-efficient and low-toxic gene delivery vectors. Nanovector-based delivery of nucleic acids is a very promising approach for the effective transfer of genetic materials into cells. Compared with encapsulating of nucleic acids inside biodegradable nanoparticles which often suffers from low encapsulation efficiency and degradation of the loaded therapeutic gene, the layer-by-layer self-assembly vectors prepared by the surface adsorption of gene/polycation multilayered films on colloidal particles using layer-by-layer technique are a potent gene delivery system in offering efficient loading of nucleic acids, controlling the release of the loaded gene in physiological environment and targeting to a particular site or a specific cell type in the body. This review focuses on the preparation, advantages, application and the probable associated drawbacks of layer-by-layer self-assembly vectors for gene delivery.     

Novel carboxymethylcellulose-based microporous hydrogels suitable for drug delivery

Several materials capable of acting as structures for controlled release were analysed for the fabrication of matrices. Among those used, hydrophilic polysaccharides appeared to be the most suitable materials. Carboxymethylcellulose (a semi-synthetic polysaccharide) was chemically cross-linked with a 60% and 90% cross-linking degree in order to obtain hydrogels and utilised as matrix for the realisation of controlled drug release systems. The morphology of the gels was changed in order to obtain a microporous structure with different porosity (14, 30 and 40 microm). The obtained porous matrices were characterised in terms of pore density, dimension and swelling behaviour. The influence of both the pore dimension and technique of loading on the release kinetics was analysed. By increasing the pore dimension the release of ibuprofen-lysin was slower. Inducing the microporous structure after the loading of the hydrogel with the drug resulted in a slower release.