A PEDF N-terminal peptide protects the retina from ischemic injury when delivered in PLGA nanospheres

The neuroprotective effects of small pigment epithelium-derived factor (PEDF) peptides injected intravitreally as free peptides or delivered in poly(lactide-co-glycolide) (PLGA) nanospheres, were tested in retinal ischemic injury. We induced transient ischemia in C57BL/6 mice by elevating the intraocular pressure to the equivalent of 120 mmHg for 60 min, then injected these eyes with one of the following: PBS, full-length native PEDF, N-terminal peptides-PEDF(136-155) and PEDF(82-121), blank PLGA nanospheres or PLGA loaded with PEDF(82-121) (PLGA-PEDF(82-121)). Morphometric analysis and TUNEL assays were used to determine the extent of retinal damage. Transient ischemia caused a rapid reduction in the number of viable cells in the retinal ganglion cell (RGC) layer over 48h as compared to non-ischemic retinas. About 76% surviving cells in the RGC layer were observed in the full-length PEDF protein treated group, whereas only 32% of cells survived in the PBS group. Thus, PEDF prevented approximately 44% of the cell death in the RGC layer resulting from transient ischemia. PEDF(82-121) peptide was as effective as full-length PEDF when injected as either a free peptide or delivered in PLGA nanospheres. PLGA-PEDF(82-121) showed longer-term protection of the RGC layer with no noticeable side effects at 7days. PEDF and PEDF(82-121) lessened damage to the IPL as measured by layer thickness. PEDF and PEDF(82-121) also delayed retinal responses to ischemic injury as measured by GFAP immunolabeling in Müller cells. PEDF(82-121) is an effective neuroprotective peptide in retinal ischemia. PLGA-PEDF(82-121) offers greater protection to the retina suggesting that this peptide and the method of delivering therapeutically active drugs have potential clinical advantages for longer-term treatments of retinal diseases.     

Preparation of Sterically Stabilized Human Serum Albumin Nanospheres Using a Novel Dextranox-MPEG Crosslinking Agent

Human serum albumin (HSA) nanospheres with a size less than 200 nm in diameter were prepared using a modified coacervation method and crosslinking with methyl polyethylene glycol modified oxidized Dextram (Dextranox-MPEG) which created a sterically stabilizing polyethylene oxide surface layer surrounding the nanospheres. The crosslinking efficiency and the surface characteristics of glutaraldehyde and Dextranox-MPEG crosslinked HSA nanospheres were determined and compared. The zeta potential of the Dextranox-MPEG crosslinked particles was significantly lower than that of glutaraldehyde stabilized particles. The existence of a hydrated steric barrier surrounding the nanospheres was confirmed by an electrolyte and pH induced flocculation test. The Dextranox-MPEG crosslinked nanospheres showed a significantly reduced plasma protein adsorption on the particle surface compared with glutaraldehyde crosslinked nanospheres.     

Biodegradable Nanospheres Containing Phthalocyanines and Naphthalocyanines for Targeted Photodynamic Tumor Therapy

Preparation methods of cyanoacrylic nanocapsules or nanoparticles containing phthalocyanines and naphthalocyanines are described. Nanocapsules were obtained by interfacial polymerization in an oil-in-water emulsion. Drug encapsulation efficiency depended upon drug concentration, ethanol concentration, and phthalocyanine sulfonation degree and reached 100% in some cases. Nanocapsules size ranged from 150 to 250 nm and varied with phthalocyanine sulfonation degree and pH of the aqueous phase. Nanoparticles were prepared by the addition of monomer to an aqueous phase containing hydrophilic phthalocyanine derivatives. Depending upon the pH, sizes ranged from 10 to 380 nm. Drug binding was between 75 and 80%. These new preparations could prove useful in the photodynamic treatment of tumors.     

Preparation of Biodegradable,Surface Engineered PLGA Nanospheres with Enhanced Lymphatic Drainage and Lymph Node Uptake

Purpose. Nanospheres can be utilised for the targeting of drugs and diagnostic agents to the regional lymph nodes. The surface modification of model polystyrene, (PS), and poly(lactide-co-glycolide),(PLGA), nanospheres by poly(lactide)-poly(ethylene glycol), (PLA:PEG), copolymers has been assessed by in vitro characterisation and in vivobiodistribution studies following subcutaneous administration of the nanospheres to the rat. Methods. Three PLA: PEG copolymers were investigated, with PEG chain lengths of 750, 2000 and 5000 Da. The PLA:PEG copolymers were either coated onto the surface of PS and PLGA nanospheres or used as a co-precipitate in the formation of PLGA-PLA:PEG nanospheres. Coating of the nanospheres was confirmed by an increase in their particle size and a corresponding decrease in the surface potential. The kinetics of injection site drainage and lymph node retention was determined over a 24 hour time course for naked, coated and co-precipitated nanosphere systems. Results. Dependent on the surface characteristics, the distribution of the nanospheres can be significantly modified and the lymph node localisation dramatically enhanced by coating their surfaces with PLA:PEG copolymers or by producing co-precipitate nanospheres of PLGA and PLA:PEG. Conclusions. A fully biodegradable nanosphere system has been developed with excellent lymph node targeting characteristics.     

In vitro effects of cholesteryl butyrate solid lipid nanospheres as a butyric acid pro-drug on melanoma cells: Evaluation of antiproliferative activity and apoptosis induction

Literature data show that butyric acid derivatives bear a dose-dependent differentiative anti-proliferative activity on cancer cell lines and that apoptosis induction may play a major role. Although it was recently shown that solid lipid nanospheres (SLNs) are a suitable tool for several in vivo drug administration routes, there is little available information on melanoma cell lines. This study was aimed at evaluating the anti-proliferative and apoptotic in vitro effects of cholesteryl butyrate (chol-but) SLNs on melanoma cells. Increasing concentrations of chol-but SLNs were used to test two melanoma cell lines. Both cell lines were treated with Na-butyrate (Na-but) and chol-but SLNs for viability. Those tested with chol-but SLNs were more effective than Na-butirate (3 to 72 h). The apoptotic effects of chol-but SLNs were evaluated between 3 and 72 h by annexin-V (ANX-V)/propidium iodide (PI) staining and the antiproliferative effect by PI staining. Apoptosis anti-proliferative-regulatory proteins as bcl-2, Fas/APO1 (CD95) and PCNA (PC10) were also investigated. Flow cytometric analyses evidenced a G_0/1-S transition block and a `sub-G_0/1' apoptotic peak from 0.5 to 1.0 mM butyric acid. In ANX-V/PI flow cytometric staining, a dose- and time-dependent increase in the apoptotic cell percentage (ANX-V+) coupled with a down-regulation of PC10 and bcl-2 and a parallel up-regulation of Fas/APO1 (CD95) were found in both lines started after 3 to 24 h of chol-but SLNs treatment. Results show that chol-but SLNs exerts a dose/time-dependent effect in melanoma cell apoptosis induction between 3 and 24 h and a dose but not time-dependent effect after 24 h of treatment. This revised version was published online in July 2006 with corrections to the Cover Date.     

聚乳酸载药纳米球的制备工艺及性能研究

运用均匀设计实验,以灰黄霉素为囊心物质用油包水溶剂挥发法制备灰黄霉素/聚乳酸纳米球,并且分析比较了载药微米球和纳米球的释药性能。结果表明所获得的纳米球球形较好且较为分散,粒径分布较为均一,粒径在114 nm左右。经线性回归和三次重复试验得出综合评分S为95.59,误差为3.66%,载药量为13.55%。载药微米球的释药速率较慢,而纳米球在性能上有一个“突跃”,能起到“增溶”药物的作用。     

Ultrafine Gold Nanoparticles Anchored on Pyridine-Inner-Functionalized Hollow Porous Organic Nanospheres for Highly Efficient Heterogeneous Catalysis

The development of metal nanoparticles (MNPs) loaded on porous materials with high efficiency and stability is significant importance for heterogeneous catalysis. Herein, ultrafine Au NPs are prepared and anchored on hollow porous organic nanospheres (Au@HPONs) with polylactide-b-poly(4-vinylpyridine)-b-polystyrene (PLA-b-P4VP-b-PS) triblock copolymers as precursors and pyridine as the coordination group. In this strategy, pyridine functional groups can coordinate with the Au NPs and uniformly disperse them in the carrier. Due to its hollow porous structure, high specific surface area, and physicochemical stability, the obtained Au@HPONs nanocomposite shows excellent catalytic performance and cycling ability for the oxidation of benzyl alcohol and the reduction of 4-nitrophenol.     

Topological Effects on Cyclic Co-Poly(ionic liquid)s Self-Assembly

Topological geometry of poly(ionic liquid)s (PILs), such as brush-like, knot-like, hyperbranched and randomly coiled, often exerts a strong influence on their self-assembly behaviors. As a primary topological form, the cyclic topology-derived effects have not been investigated on PILs, which concerns synergy of charges and zero chain end. Herein, linear and cyclic poly(ionic liquid) copolymers (co-PILs) with randomly distributed counter anions of B(Ph)₄⁻ and Br⁻ by a template method in combination with a follow-up partial anion exchange is prepared. The self-assembly phenomena of linear and cyclic co-PILs are studied in selective solvents, where the hydrophobic counter anions B(Ph)₄⁻ and hydrophilic counter anions Br⁻ aggregated to form cores and corona in the assembled nanospheres, showing the average size of cyclic co-PILs nanospheres is 46.2% smaller (≈120 nm) than linear co-PILs nano-assemblies (≈176 nm). Based on the CGMD simulations, the authors speculate that the spherical aggregates are formed by transitioning from micelles with gradient block-like structures, which formed by enriched hydrophobic counter anions in the core and enriched hydrophilic counter anions in the corona. These results indicate a novel synergy of topology effects and dynamic anion movements, as revealed by cyclic co-PIL self-assembly in this work.     

Chiral mesoporous silica nano-screws as an efficient biomimetic oral drug delivery platform through multiple topological mechanisms

In the microscale, bacteria with helical body shapes have been reported to yield advantages in many bio-processes. In the human society, there are also wisdoms in knowing how to recognize and make use of helical shapes with multi-functionality. Herein, we designed atypical chiral mesoporous silica nano-screws (CMSWs) with ideal topological structures (e.g., small section area, relative rough surface, screw-like body with three-dimension chirality) and demonstrated that CMSWs displayed enhanced bio-adhesion, mucus-penetration and cellular uptake (contributed by the macropinocytosis and caveolae-mediated endocytosis pathways) abilities compared to the chiral mesoporous silica nanospheres (CMSSs) and chiral mesoporous silica nanorods (CMSRs), achieving extended retention duration in the gastrointestinal (GI) tract and superior adsorption in the blood circulation (up to 2.61- and 5.65-times in AUC). After doxorubicin (DOX) loading into CMSs, DOX@CMSWs exhibited controlled drug release manners with pH responsiveness in vitro. Orally administered DOX@CMSWs could efficiently overcome the intestinal epithelium barrier (IEB), and resulted in satisfactory oral bioavailability of DOX (up to 348%). CMSWs were also proved to exhibit good biocompatibility and unique biodegradability. These findings displayed superior ability of CMSWs in crossing IEB through multiple topological mechanisms and would provide useful information on the rational design of nano-drug delivery systems.     

Size-Controlled Synthesis of Soluble-Conjugated Polymeric Nanoparticles in Dendritic Mesoporous Silica Nanospheres

A size-controlled method has been exploited to synthesize 20 kinds of soluble-conjugated polymeric nanoparticles (SCPNs) through cross-coupling polymerizations between various combinations of symmetrical multifunctional monomers (A_x+B_y, x > 2, y ≥ 2). Unlike the classical polycondensation of these kinds of monomers where infinite polymer networks and insoluble polymeric products are typically formed, this confined polymerization in palladium nanoparticles-loaded dendritic mesoporous silica nanospheres produced SCPNs with good to high yields, narrow particle size distribution, and high solubility in common organic solvents. The controlled size of SCPNs characterized with gel permeation chromatography shows narrow distribution and various molecular weight ranging from 2164 to 14 234 Da, transmission electron microscopy and dynamic light scattering analyses range from 5 to 15 nm, suggesting the confined polymerization occurring inside of the mesopores. By simply adjusting the monomer structure and selecting an appropriate cross-coupling polymerization method among Suzuki, Stille, Sonogashira, and direct arylation polymerizations, the obtained SCPNs show bright fluorescence emission varying from blue to red. The SCPNs with long alkyl chain substituents in monomer units show good processability and smooth polymer films are formed by the simple spin-casting method. The repeatable and straightforward synthesis of SCPNs endows them with wide application prospects in light-emission, fluorescence sensing, and bioimaging.