HPMC improves protective effects of naringenin and isonicotinamide co-crystals against abdominal aortic aneurysm.

PURPOSE: Abdominal aortic aneurysm (AAA) rupture is one of the most common causes of mortality in cardiovascular diseases, but currently there is no approved drug for AAA treatment or prevention in the clinic. Naringenin (NGN) has been reported to have anti-AAA effects. However, water solubility and in vivo absorption of NGN are not satisfactory, which leads to its low bioavailability, thus affecting its pharmacological effects. In this project, the improving effects of isonicotinamide (INT) co-crystal and hydroxy propyl methyl cellulose (HPMC) or polyvinyl pyrrolidone (PVP) on the solubility, in vivo absorption, and anti-AAA effects of NGN were evaluated. METHODS: In the current study, co-crystals of naringenin-isonicotinamide (NGN-INT) were prepared, and effects of PVP or HPMC on precipitation rate, supersaturation, and bioavailability of NGN were explored. In addition, with or without HPMC supply, the effects of NGN-INT co-crystal on anti-AAA efficacy of NGN were investigated on an elastase-induced AAA mouse model, and the results were compared with the efficacy of the NGN crude drug. RESULTS: Our results demonstrate that NGN-INT formulation, compared to the NGN crude drug, enhanced the dissolution rate of NGN and significantly increased Cmax and AUC(0-∞) of NGN by 18 times and 1.97 times, respectively. Addition of PVP or HPMC in NGN-INT co-crystal further increased bioavailability of NGN in NGN-INT. The in vivo pharmacodynamic study showed that NGN-INT with HPMC significantly improved the inhibitory effects of NGN against AAA. CONCLUSION: NGN-INT significantly improved the absorption and aortic protective effects of NGN. The supersaturation-prolonging effect of HPMC further enhanced bioavailability and anti-AAA effects of NGN-INT.

Polyurethane Nanoparticle-Loaded Fenofibrate Exerts Inhibitory Effects on Nonalcoholic Fatty Liver Disease in Mice.

Polyurethane (PU) nanoparticles are potential drug carriers. We aimed to study the in vitro and in vivo efficacy of biodegradable PU nanoparticles loaded with fenofibrate (FNB-PU) on nonalcoholic fatty liver disease (NAFLD). FNB-PU was prepared by a green process, and its preventive effects on NAFLD were investigated on HepG2 cells and mice. FNB-PU showed sustained in vitro FNB release profile. Compared to FNB crude drug, FNB-PU significantly decreased triglyceride content in HepG2 cells incubated with oleic acid and in livers of mice with NAFLD induced by a methionine choline deficient diet, and increased plasma FNB concentration of the mice. FNB-PU increased absorption of FNB and therefore enhanced the inhibitory effects of FNB on NAFLD.

Fenofibrate nanoliposome: Preparation and its inhibitory effects on nonalcoholic fatty liver disease in mice.

The aim was to prepare fenofibrate nanoliposome (FNB-Nanolipo) and investigate its characterizations, oral pharmacokinetic (PK) profiles as well as preventive and therapeutic effects on nonalcoholic fatty liver disease (NAFLD) induced by a methionine choline deficient (MCD) diet in mice. The prepared FNB-Nanolipo showed high drug loading capacity and sustained in vitro FNB release profile. Compared to FNB crude drug at equal doses, the FNB-Nanolipo given at 20 mg/kg/day (beginning on the same day when the MCD diet feeding started and lasted for 7 days) or 40 mg/kg/day (beginning after 7 days of the MCD diet feeding and lasting for another 7 days together with the MCD diet) increased plasma FNB concentration of the mice by 11.8-fold (P<0.05) or 57.3-fold (P<0.001), respectively, and reduced 54.7% (P<0.05) or 35.5% (P<0.05) of excessive hepatic lipid, respectively. The results suggest that the FNB-Nanolipo could not only significantly prevent but also efficiently treat NAFLD.

Preventive effects of simvastatin nanoliposome on isoproterenol-induced cardiac remodeling in mice.

In this study, simvastatin (SMV) and SMV nanoliposome (SMV-Lipo) were given to male BALB/c mice by either intragastric (i.g.) or intraperitoneal (i.p.) administration, and their effects on isoproterenol (ISO)-induced cardiac remodeling were compared. The results indicate that by i.p. administration, the SMV-Lipo at an equal SMV dose exhibited more significant inhibitory effects than the crude SMV on cardiac hypertrophy, fibrosis and inflammation. Comparing the SMV-Lipo on different administration regimens, i.p. group showed more significant inhibitory effects on cardiac remodeling than i.g. group. In addition, pharmacokinetic studies revealed that SMV-Lipo administrated by either i.p. or i.g. more significantly improved the plasma SMV concentration than the crude SMV. Therefore, the SMV-Lipo significantly enhanced the inhibitory effects of SMV on cardiac remodeling resulted from the enhanced absorption of SMV by nanoliposome formulation, and i.p. was better than i.g. administration.

Oral absorption enhancement of probucol by PEGylated G5 PAMAM dendrimer modified nanoliposomes.

Probucol (PB), an antioxidant drug, is commonly used as a lipid concentration lowering drug to reduce blood plasma cholesterol levels in the clinic. However, the therapeutic effects of this drug are negatively impacted by its poor water solubility and low oral absorption efficiency. In this study, a PEGylated G5 PAMAM dendrimer (G5-PEG) modified nanoliposome was employed to increase water solubility, transepithelial transport, and oral absorption of PB. The uptake mechanism was explored in vitro in Caco-2 cells with the results suggesting that the absorption improvement of G5-PEG modified PB-liposome (PB-liposome/G5-PEG) was related to P-glycoprotein (P-gp) efflux pump but was independent of caveolae endocytosis pathways. Additionally, plasma lipid concentration lowering effects of PB-liposome/G5-PEG were evaluated in vivo in a LDLR-/- hyperlipidemia mouse model. Compared with saline treated group, treatment with PB-liposome/G5-PEG significantly inhibited the increase of plasma total cholesterol (TC) and triglyceride (TG) of mice induced by a high fat diet. Moreover, its lipid concentration lowering effects and plasma drug concentration were greater than PB alone or commercial PB tablets. Our results demonstrated that PB-liposome/G5-PEG significantly increased the oral absorption of PB and therefore significantly improved its pharmacodynamic effects.

G5 PAMAM dendrimer versus liposome: a comparison study on the in vitro transepithelial transport and in vivo oral absorption of simvastatin.

This study compared formulation effects of a dendrimer and a liposome preparation on the water solubility, transepithelial transport, and oral bioavailability of simvastatin (SMV). Amine-terminated G5 PAMAM dendrimer (G5-NH2) was chosen to form SMV/G5-NH2 molecular complexes, and SMV-liposomes were prepared by using a thin film dispersion method. The effects of these preparations on the transepithelial transport were investigated in vitro using Caco-2 cell monolayers. Results indicated that the solubility and transepithelial transport of SMV were significantly improved by both formulations. Pharmacokinetic studies in rats also revealed that both the SMV/G5-NH2 molecular complexes and the SMV-liposomes significantly improved the oral bioavailability of SMV with the liposomes being more effective than the G5-NH2. The overall better oral absorption of SMV-liposomes as compared to SMV/G5-NH2 molecular complexes appeared to arise from better liposomal solubilization and encapsulation of SMV and more efficient intracellular SMV delivery. FROM THE CLINICAL EDITOR: Various carrier systems have been designed to enhance drug delivery via the oral route. In this study, the authors compared G5 PAMAM dendrimers to liposome preparations in terms of solubility, transepithelial transport, and oral bioavailability of this poorly water-soluble drug. This understanding has improved our knowledge in the further development of drug carrier systems.

Impacts of polypropylene microplastics on the distribution of cadmium, enzyme activities, and bacterial community in black soil at the aggregate level.

Microplastics (MPs) can co-occur widely with heavy metals in soil. This study intended to investigate the influences of the co-exposure of polyethylene MPs (0.5 %, w/w) and cadmium (Cd) in black soil on the Cd distribution, enzyme activities, and bacterial communities in both bulk soil and different sized soil aggregates (> 1, 0.50-1, 0.25-0.50, and < 0.25 mm aggregates) after a 90-day incubation. Our results showed that the existence of MPs increased the distributions of Cd in >1 mm and < 0.25 mm soil aggregates and decreased its distributions in 0.50-1 mm and 0.25-0.50 mm soil aggregates. About 12.15 %-17.65 % and 9.03 %-11.13 % of Cd were distributed in the exchangeable and oxidizable forms in bulk soil and various sized soil aggregates after the addition of MPs which were higher than those in the only Cd-treated soil (11.17 %-14.72 % and 8.66 %-10.43 %, respectively), while opposite tendency was found for Cd in the reducible form. Urease and ß-glucosidase activities in the Cd-treated soils were 1.14-1.18 and 1.07-1.31 times higher than those in the Cd-MPs treated soils. MPs disturbed soil bacterial community at phylum level and increased the bacteria richness in bulk soil. The levels of predicted functional genes which are linked to the biodegradation and metabolism of exogenous substances and soil C and N cycles were altered by the co-exposure of Cd and MPs. The findings of this study could help deepen our knowledge about the responses of soil properties, especially microbial community, to the co-occurrence of MPs and heavy metals in soil.

3D-Printed proangiogenic patches of photo-crosslinked gelatin and polyurethane hydrogels laden with vascular cells for treating vascular ischemic diseases.

Engineering vascularized tissues remains a promising approach for treating ischemic cardiovascular diseases. The availability of 3D-bioprinted vascular grafts that induce therapeutic angiogenesis can help avoid necrosis and excision of ischemic tissues. Here, using a combination of living cells and biodegradable hydrogels, we fabricated 3D-printed biocompatible proangiogenic patches from endothelial cell-laden photo-crosslinked gelatin (EC-PCG) bioink and smooth muscle cell-encapsulated polyurethane (SMC-PU) bioink. Implantation of 3D-bioprinted proangiogenic patches in a mouse model showed that EC-PCG served as an angiogenic capillary bed, whereas patterned SMC-PU increased the density of microvessels. Moreover, the assembled patterns between EC-PCG and SMC-PU induced the geometrically guided generation of microvessels with blood perfusion. In a rodent model of hindlimb ischemia, the vascular patches rescued blood flow to distal tissues, prevented toe/foot necrosis, promoted muscle remodeling, and increased the capillary density, thereby improving the heat-escape behavior of ischemic animals. Thus, our 3D-printed vascular cell-laden bioinks constitute efficient and scalable biomaterials that facilitate the engineering of vascular patches capable of directing therapeutic angiogenesis for treating ischemic vascular diseases.

Efficient in vitro siRNA delivery and intramuscular gene silencing using PEG-modified PAMAM dendrimers.

Although siRNA techniques have been broadly applied as a tool for gene knockdown, substantial challenges remain in achieving efficient delivery and in vivo efficacy. In particular, the low efficiency of target gene silencing in vivo is a critical limiting step to the clinical application of siRNA therapies. Poly(amidoamine) (PAMAM) dendrimers are widely used as carriers for drug and gene delivery; however, in vivo siRNA delivery by PAMAM dendrimers remains to be carefully investigated. In this study, the effectiveness of G5 and G6 PAMAM dendrimers with 8% of their surface amines conjugated to MPEG-5000 was studied for siRNA delivery in vitro and for intramuscular in vivo delivery in mice. The results from the PEG-modified dendrimers were compared to the results from the parent dendrimers as well as Lipofectamine 2000 and INTERFERin. Both PEG-modifed dendrimers protect the siRNA from being digested by RNase and gave high transfection efficiency for FITC-labeled siRNA in the primary vascular smooth muscle cells (VSMC) and mouse peritoneal macrophages. The PEG-modified dendrimers achieved knockdown of both plasmid (293A cells) and adenovirus-mediated green fluorescence protein (GFP) expression (Cos7 cells) in vitro with efficiency similar to that shown for Lipofectamine 2000. We further demonstrated in vivo that intramuscular delivery of GFP-siRNA using PEG-modified dendrimer significantly suppressed GFP expression in both transiently adenovirus infected C57BL/6 mice and GFP transgenic mice.

Multiple fluorescence labeling and two dimensional FTIR-13C NMR heterospectral correlation spectroscopy to characterize extracellular polymeric substances in biofilms produced during composting.

Knowledge on the structure and function of extracellular polymeric substances (EPS) in biofilms is essential for understanding biodegradation processes. Herein, a novel method based on multiple fluorescence labeling and two-dimensional (2D) FTIR-(13)C NMR heterospectral correlation spectroscopy was developed to gain insight on the composition, architecture, and function of EPS in biofilms during composting. Compared to other environmental biofilms, biofilms in the thermophilic (>55 °C) and cooling (mature) stage of composting have distinct characteristics. The results of multiple fluorescence labeling demonstrated that biofilms were distributed in clusters during the thermophilic stage (day 14), and dead cells were detected. In the mature stage (day 26), the biofilm formed a continuous layer with a thickness of approximately 20-100 µm around the compost, and recolonization of cells at the surface of the compost was easily observed. Through 2D FTIR-(13)C NMR correlation heterospectral spectroscopy, the following trend in the ease of the degradation of organic compounds was observed: heteropolysaccharides > cellulose > amide I in proteins. And proteins and cellulose showed significantly more degradation than heteropolysaccharides. In summary, the combination of multiple fluorescence labeling and 2D correlation spectroscopy is a promising approach for the characterization of EPS in biofilms.

[Compound erythromycin sustained release preparation and its in vitro release].

Using the weight-average molecular weight 50 000 polylactic acid (PLA) as a carrier, and a certain proportion of erythromycin (EM) and prednisone acetate (PNA) to mixed prepare the compound erythromycin sustained release preparation (sustained-release tablets). Using ultraviolet spectrophotometry and high performance liquid chromatography (HPLC) to detect separately the release amount of EM and PNA in vitro medium. The sustained-release tablets release for about 21 days, the average content of EM is 99.7 mg/table, RSD = 0.82%; and the average content of PNA is 10.03 mg/table, RSD = 0.93%. Within 21 days, the cumulative releases of EM and PNA are 86.1% and 78.3%, respectively. The drug release is steady and slow after 5 days, the burst release phenomenon in early stage is more significant. The results showed that the sustained-release tablet preparation method is feasible, the release performance is good and the clinical efficacy is significant.

Recent advances of dendrimers in delivery of genes and drugs.

Dendrimers as a new kind of polymer have been studied for medical applications mainly in two aspects: drug delivery and gene delivery. The unique characteristics, such as uniformity, monodispersity and the ability to functionalize their terminal groups with various targeting agents distinguish them as versatile carriers. In the paper the recent advances of dendrimer in gene transfer vehicles and drug delivery are separately reviewed. These advances illustrate the direction of the future development of dendrimers.

Treatment outcomes in a graduate orthodontic clinic for cases defined by the American Board of Orthodontics malocclusion categories.

INTRODUCTION: The American Board of Orthodontics (ABO) discrepancy index (DI) quantifies the severity of a malocclusion. The ABO objective grading system (OGS) assesses the quality of orthodontic finishing. Indiana University's comprehensive clinical assessment (CCA) supplements the OGS to provide an instrument to determine clinical outcomes. The purposes of this article were to (1) determine whether treatment outcome is related to the type of malocclusion as defined by the ABO classification, (2) determine the fraction of finished orthodontic cases in the graduate orthodontics clinic that are within the ABO standards for passing the phase III clinical examination, (3) evaluate the contribution of each component of the OGS and the CCA to the total OGS and CCA scores, (4) determine the percentage of finished cases that meet the ABO case category specifications, and (5) identify problem areas to improve the quality of treatment for challenging malocclusions. METHODS: Three hundred eighty-two cases that satisfied requirements for 8 of the ABO's malocclusion categories were selected from 989 consecutively finished cases from 1998 through 2003. They were evaluated by using the OGS, the CCA, and the DI. RESULTS: The average OGS score was 32.64, the average CCA score was 5.62, and the average DI score was 20.94. There was no significant difference in the OGS and the CCA scores among the categories. Categories 2, 5, 7, and 8 had a DI score that was significantly higher than the average for the entire sample. The OGS and CCA scores were positively correlated with the DI score, meaning that complex malocclusions are challenging to finish well. The most points lost for the OGS and the CCA were for occlusal contacts and treatment efficiency (length of treatment relative to the result), respectively. The fewest points lost were for interproximal contacts and vertical control, respectively. Furthermore, prematurely terminated cases (early debonds) had longer treatment times and higher (worse) OGS and CCA scores. CONCLUSIONS: This study demonstrates problems in treating complex malocclusions in a graduate orthodontics program and suggests methods for increasing the quality of clinical outcomes.

Thermosensitive Hydrogel Containing Doxycycline Exerts Inhibitory Effects on Abdominal Aortic Aneurysm Induced By Pancreatic Elastase in Mice.

Doxycycline (DOX) is reported to exert therapeutic effects against abdominal aortic aneurysm (AAA), a severe degenerative disease. In this study, a DOX hydrogel formulation of DOX/PECTgel is studied, and its phase transition behavior and in vitro release profiles are explored. In addition, the anti-AAA effects and bioavailability of DOX/PECTgel are evaluated in an elastase induced AAA mouse model. The results show that the phase transition temperature of 30% poly(e-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT) solution is above 34 °C. In vitro release profiles of DOX/PECTgel indicate a fast release of DOX at the first two days, followed by a slow and sustained release for 14 d. In vivo single-dose single subcutaneous injection of DOX/PECTgel containing 8.4 or 4.2 mg mL-1 DOX presents comparatively preventive effects on AAA, compared to intraperitoneal injections of DOX alone at a dose of 15 mg kg-1 for seven injections, while DOX bioavailability of the DOX/PECTgel treated groups is 1.39 times or 1.19 times of the DOX alone treated group, respectively.

Efficient siRNA Delivery Using PEG-conjugated PAMAM Dendrimers Targeting Vascular Endothelial Growth Factor in a CoCl2-induced Neovascularization Model in Retinal Endothelial Cells.

BACKGROUND: Choroidal neovascularization (CNV), also known as subretinal neovascularization, causes serious damage to the central vision as it happens more commonly in macula. The most important factor involved in angiogenesis is vascular endothelial growth factor (VEGF). By an RNAi technique, VEGF gene knockdown can be used to treat CNV. PEG-conjugated poly (amidoamine) (PEGPAMAM) dendrimers as a new type of synthetic polymers are very promising to be gene delivery carriers. METHODS: To investigate siRNA delivery efficacy of PEG-PAMAM dendrimers, we prepared dendriplexes of PEG-PAMAM dendrimers with a fluorescence-labelled siRNA (PEG-PAMAM/FAM siRNA) or VEGF siRNA (PEG-PAMAM/VEGF siRNA), and studied transfection and downregulation efficacy of the dendriplexes in a cobalt chloride (CoCl2)-induced neovascularization model in retinal vascular endothelial cells (RF/6A). RESULTS: Our results demonstrate that PEG-PAMAM dendrimers had significantly higher transfection efficiency to FAM siRNA than a commercial transfection reagent PEI (1.4-fold, P<0.001) measured by flow cytometry. Compared to the PEI/VEGF siRNA polyplexes, the dendriplexes of the PEG-PAMAM/VEGF siRNA more significantly downregulated VEGF gene expression (P < 0.01) at both mRNA and protein expression level. A tube formation assay also proved that the PEG-PAMAM/VEGF siRNA dendriplexes more significantly inhibited vascular-like formation than PEI/VEGF siRNA did (P < 0.001) in RF/6A. CONCLUSION: This study demonstrated that G5-PEG was more efficient than PEI in facilitating siRNA delivery, downregulating VEGF expression and inhibiting vascular-like formation on RF/6A.

Electrospinning of calcium phosphate-poly (d,l-lactic acid) nanofibers for sustained release of water-soluble drug and fast mineralization.

Calcium phosphate-based biomaterials have been well studied in biomedical fields due to their outstanding chemical and biological properties which are similar to the inorganic constituents in bone tissue. In this study, amorphous calcium phosphate (ACP) nanoparticles were prepared by a precipitation method, and used for preparation of ACP-poly(d,l-lactic acid) (ACP-PLA) nanofibers and water-soluble drug-containing ACP-PLA nanofibers by electrospinning. Promoting the encapsulation efficiency of water-soluble drugs in electrospun hydrophobic polymer nanofibers is a common problem due to the incompatibility between the water-soluble drug molecules and hydrophobic polymers solution. Herein, we used a native biomolecule of lecithin as a biocompatible surfactant to overcome this problem, and successfully prepared water-soluble drug-containing ACP-PLA nanofibers. The lecithin and ACP nanoparticles played important roles in stabilizing water-soluble drug in the electrospinning composite solution. The electrospun drug-containing ACP-PLA nanofibers exhibited fast mineralization in simulated body fluid. The ACP nanoparticles played the key role of seeds in the process of mineralization. Furthermore, the drug-containing ACP-PLA nanofibers exhibited sustained drug release which simultaneously occurred with the in situ mineralization in simulated body fluid. The osteoblast-like (MG63) cells with spreading filopodia were well observed on the as-prepared nanofibrous mats after culturing for 24 hours, indicating a high cytocompatibility. Due to the high biocompatibility, sustained drug release, and fast mineralization, the as-prepared composite nanofibers may have potential applications in water-soluble drug loading and release for tissue engineering.

G5-PEG PAMAM dendrimer incorporating nanostructured lipid carriers enhance oral bioavailability and plasma lipid-lowering effect of probucol.

This work aimed to improve the oral bioavailability and plasma lipid-lowering effect of probucol (PB) by constructing a combined drug delivery system (CDDS) composed of nanostructured lipid carrier (NLC) and PEGylated poly(amidoamine) dendrimer (PEG-PAMAM). PEG-PAMAM with dendrimer generations of 5 (G5-PEG) or 7 (G7-PEG) were incorporated in PB-NLCs to form PB-CDDSs, PB-NLCs/G5-PEG and PB-NLCs/G7-PEG. The resultant two kinds of PB-CDDSs were characterized by particle size, zeta potential, drug encapsulation efficacy, PB release rates, and physical stability. Formulation effects of NLC and CDDS on the cellular uptake of hydrophobic drug were explored in Caco-2 cells by fluorescent Cy5 dye as a hydrophobic drug model. Furthermore, in vivo pharmacokinetics of the PB-CDDS composed of G5-PEG and PB-NLCs were investigated in a low density lipoprotein receptor knockout (LDLr-/-) mouse model, including plateau plasma PB concentrations after oral administration of multiple doses, and bioavailability after oral administration of a single dose of different PB formulations. In addition, lipid-lowering effect of PB-NLCs/G5-PEG was studied. The results indicate that both G5-PEG and G7-PEG significantly improved aqueous solubility of PB. The two PB-CDDSs exhibited similar particle size (around 150nm) as PB-NLCs, but slower PB burst release rate, higher total PB release amount, and better particle morphology and storage stability than PB-NLCs. In comparison with traditional NLC, CDDS dramatically enhanced cellular uptake of Cy5 into Caco-2 cells. In vivo results demonstrate that PB-NLCs/G5-PEG had the highest plateau plasma PB concentration and oral bioavailability, and the greatest cholesterol-lowering effect in comparison with PB suspensions and PB-NLCs. Therefore, G5-PEG incorporating NLC can be exploited as a promising drug delivery system to improve oral bioavailability and lipid-lowering effect of PB.

[Studies on the changes in rice straw composition in relay treatment of chemical-microbial process by FTIR spectroscopy].

Direct burning of crop straw in the field has given or is giving rise to a serious pollution of atmosphere. The difficult decomposing of the crop straw by soil microorganisms is one of the reasons the crop straw is not popularly used in agriculture. Fourier transform infrared spectroscopy (FTIR) was used to study the changes in straw composition during the relay treatment of chemical-microbial process. The results showed that the method of FTIR spectra could indicate the changes in straw composition during the treatment processes. After the relay treatment of chemical-microbial process, the contents of cellulose, semi-cellulose, and silicon, and C/N ratio were decreased significantly, while the water soluble substances were increased, which was in accordance with the results of chemical analysis. The method to treat crop straw proposed in this paper could provide a practicable way in agricultural utilization of crop straw.

The role of caveolin-1 and syndecan-4 in the internalization of PEGylated PAMAM dendrimer polyplexes into myoblast and hepatic cells.

To improve gene delivery efficiency of PEGylated poly(amidoamine) dendrimers in livers and muscles, the roles of syndecan-4 receptor and caveolin-1 protein in the endocytosis of PEGylated generation 5 (G5-PEG) or 7 (G7-PEG) dendrimers and plasmid DNA polyplexes were explored in C2C12 and HepG2 cells. Expression levels of syndecan-4 for both cell lines were downregulated by transfection of the cells with syndecan-4 specific siRNA. Caveolin-1 was upregulated by infecting the cells with adenovirus vector expressed caveolin-1 (Ad-CAV-1). The impact of syndecan-4 and caveolin-1 on endocytosis of G5-PEG/DNA or G7-PEG/DNA polyplexes was then measured by flow cytometry. Our results demonstrate that downregulation of syndecan-4 and upregulation of caveolin-1 significantly improved internalization of PEG-PAMAM dendrimer polyplexes in HepG2 cells; however, in C2C12 cells, downregulation of syndecan-4 decreased the internalization of the polyplexes while upregulation of caveolin-1 had no effect on internalization. Gene expression results for G5-PEG/pGFP on the two cell lines exhibited the same trends for syndecan-4 and caveolin-1 as was observed for endocytosis of the polyplexes. This study gives a clue how to take strategies by up- or down-regulation of the expressions of syndecan-4 and caveolin-1 to improve in vivo gene delivery efficiency of the PEG-PAMAM dendrimers in clinical transgenic therapy.

Amorphous calcium phosphate nanospheres/polylactide composite coated tantalum scaffold: facile preparation, fast biomineralization and subchondral bone defect repair application.

Calcium phosphate (CaP) materials are widely used in various biomedical areas such as drug/gene delivery and bone repair/tissue engineering. In this study, amorphous CaP nanospheres synthesized by a simple co-precipitation method are used to prepare the CaP-polylactide (CaP-PLA) composite. Then, the as-prepared CaP-PLA composite is used to coat tantalum (Ta) plates and porous scaffolds. Compared with bare Ta plate, CaP-PLA coated Ta plates show a high performance of surface biomineralization in simulated body fluid (SBF). In addition, the hydrophilicity of the CaP-PLA coated Ta plates is significantly improved. CaP-PLA coated Ta plates with bovine serum albumin (BSA) are prepared and used for the investigation of BSA release in vitro. The experimental results indicate a sustained BSA release property and simultaneous biomineralization of the as-prepared BSA-containing CaP-PLA coated Ta plates. Furthermore, CaP-PLA coated Ta scaffolds are favorable for the human osteoblast-like MG63 cells adhesion and spreading. The vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-containing CaP-PLA coated porous Ta scaffolds are used for the study of rabbit subchondral bone defect repair, covering with autogeneic periosteums. The as-prepared CaP-PLA composite coated Ta scaffolds are useful to guide the bone regeneration in vivo.