Polylactic Glycolic Acid Research Articles

Preparation and Characterization of Vancomycin-Loaded Microsphere Composite Scaffolds

Objective: To fabricate and characterize sustained release antibacterial microsphere composite scaffolds for bone tissue engineering. Methods: First, poly(lactic acid glycolic acid) (PLGA) copolymer, chitosan (CS), and hyaluronic acid (HA) were used to prepare porous microspheres by the emulsion method. Vancomycin (VA) hydrochloride was loaded onto the microspheres (VA@PLGA-CS-HA) for sustained release of drug, after which hydroxyapatite (HAP) was added (VA@PLGA-CS-HA/HAP). The detailed in vitro characterization of the antibacterial sustained-release microspheres was performed using various techniques including the Cell Counting Kit-8 assay; hemolysis, osteogenic, and antibacterial experiments; scanning electron microscopy (SEM); and mechanical testing. Results: SEM showed that the sustained-release PLGA-CS-HA microspheres had a regular spherical shape, and the composite scaffolds of VA@PLGA-CS-HA/HAP microspheres were compact in structure. The relative colony-forming unit was less than 3% after 14 d of intervention. Cytotoxicity testing revealed that the relative growth rate of MC3T3-E1 and MG-63 osteoblast cells was more than 80% when the concentration of VA did not exceed 50 mg/mL. The mechanical strength of the scaffolds was comparable to that of human cancellous bone. The composite scaffolds enhanced the alkaline phosphatase activity of MG-63 cells and promoted the mRNA expression of osteogenic genes such as runt-related transcription factor 2, osteocalcin, osteopontin, and collagen. Conclusion: VA@PLGA-CS-HA microspheres can control the slow and sustained release of VA in vitro. The VA@PLGA-CS-HA/HAP microsphere composite scaffolds has a slower degradation rate and good antibacterial and mechanical properties in vitro.

Influence of Administration Route and Dose on Biodistribution Profile and Effects of PEG-PLA Nanoparticles in Mice

Polyethylene glycol-polylactic acid nanoparticles (PEG-PLA NPs) represent a new generation of parenteral therapeutics systems. Following administration, these NPs possess the potential to interact with biological machinery. Therefore, it is essential to get a systematic understanding of the biological fate of these NPs to evaluate their safety. In the present study, two doses (20 and 40 mg/kg) of technetium-99m labeled PEG-PLA NPs were administered intravenous (i.v.) and oral into mice and the distribution was assessed at 1, 2, 4 and 24 h post administration. Biodistribution and blood kinetic profiles revealed the extended systemic circulation of the NPs. Dose-dependent presence of NPs (p<0.05) was detected in the blood, liver, lung, spleen, and kidney of i.v. injected mice, and also in the blood, lung, spleen, stomach, and intestine of oral administered mice. The consequences of NP interaction with the biological components were studied by measurement of hematology, oxidative stress, genotoxic and histological parameters. Significantly increased levels of oxidative stress markers such as glutathione were observed in the liver, and spleen of i.v. injected mice and liver, stomach, and intestine of orally treated mice. Decreased lipid peroxidation levels (p<0.05) were observed in the liver of orally treated mice versus untreated mice. Even though PEG-PLA NPs have been shown to induce oxidative DNA damage, interestingly no histological lesions were observed in selected organs except lung of i.v. treated mice, which showed moderate vascular congestion. Such insights on in vivo distribution and understanding of nano-bio interactions at molecular and genetic levels are considered fundamental for the designing of safer nanoparticles for biomedical applications.

Simultaneous doxorubicin encapsulation and in-situ microfluidic micellization of bio-targeted polymeric nanohybrids using dichalcogenide monolayers: A molecular in-silico study

The rate of Riboflavin (RF) consumption in cancerous cells is interestingly high and this might imply the use of RF ligand in nanocarriers in order to target anticancer drugs into cancer cells. This study aimed to develop a hybrid drug carrier of Doxorubicin (DOX) loaded on RF targeted micelles composed of hydrophobic polylactic-glycolic acid (PLGA) and hydrophilic polyethylene glycol (PEG). In this regard, a simultaneous encapsulation of DOX and in-situ micellization as well as the self-assembly of PLGA-PEG-RF molecules were investigated. Moreover, the effects of microfluidic environment and transition metal dichalcogenide (TMD) nanolayers on the micellization properties (e.g., stability, size, and self-assembly interaction energies) of nanocarriers were simulated for the first time. To this purpose, the simulations were performed using two non-microfluidic methods as well as a novel microfluidic one. The molecular simulations revealed that all of the selected TMDs, especially MoSe2, had a great impact on the stability and size of nanocarriers. MoSe2 significantly enhanced the loading capacity as well as the stability of RF-targeted micelles and reduced the size of nanocarriers. Likewise, the results of various analyses demonstrated that the microfluidic method is the most effective way to synthesize nanocarriers with higher stability and smaller particle size. Hence, the use of MoSe2 monolayer, micelle containing RF, and microfluidic method were believed to be the best approach in order to improve the quality of micelles. The present work sheds new light on the use of TMDs in the synthesis of smart carriers for cancer treatment.

MiR-199a-3p Inhibitor Delivered Through Nano-Drug Delivery Systems Suppresses Tumor Cell Survival and Metastasis

Gastric cancer (GC) is a life-threatening malignant tumor present in the digestive tract. In this study the connection of miR-199a-3p, which is a gene abnormally expressed in GC, was analyzed along with the pathological parameters as well as the prognosis of GC patients. Moreover, the influence of miR-199a-3p inhibitor delivered through the nano-drug delivery system (NDDS) was studied in regard of GC cell survival and metastasis, seeking to reveal its potential treatment effect. During the conduction of the study, high miR-199a-3p expression was detected in GC tissues, sera, and cells along with its value for GC screening and pathological progression. In molecular research, polylactic-glycolic acid (PLGA) nanoparticles (NPs)-miRNA complexes that shaped like symmetrical spheres under the scanning electron microscope (SEM) were prepared to increase or decrease the levels of miR-199a-3p. The GC cell survival and metastasis was remarkably facilitated by the elevated miR-199a-3p, and its knockdown produced an opposite effect to markedly inhibit GC cell survival and metastasis. In conclusion, the expression in GC patients was increased by miR-199a-3p and the ability of its inhibitor delivered through the NDDS was demonstrated to control the survival and metastasis of GC cells.

Biodegradable Porous Microneedle for Electric Skin Patch

Oral drugs administrate to a body with painless and low cost, however, the efficiency of most oral drugs is not high due to the metabolic degradation during adsorption process. In contrast, a skin patch-based transdermal drug delivery is attractive for avoiding the route of metabolic degradation, as well as its painless property. In order to improve the transdermal drug delivery, microneedle array has been of much interest since it can reach inside stratum corneum and enhance the transdermal adsorption of the drugs. Different types of microneedles of the drug-coated, the dissolvable, and the hollowed structure have been applied for skin patches. In the previous study, we have developed porous microneedles (PMN) consisting of glycidyl methacrylate (GMA) by using the porogen method with polyethylene glycol (PEG), which allowed fast water absorption and enough mechanical strength to reach into the skin [1]. Moreover, the GMA-PMN was proved to decrease the transdermal ionic resistance [2], and thus is expected to enhance the iontophoresis efficiency. However, since the tip of GMA-PMN remained in the body is hard to be metabolized, an adverse effect on the human body could be cased. In this study, we developed PMNs consisting of a biodegradable material, polylactic acid-glycolic acid copolymer (PLGA) (Figure 1A). In order to improve the hydrophilicity and mechanical strength of the PLGA-PMNs, the water-soluble and biodegradable polymer was composited to the PLGA-PMNs.The PMN were fabricated by a combination of molding method and freeze-drying. PLGA dissolved in 1,4-dioxane was filled into a PDMS mold, frozen in a freezing chamber, and dried in a freeze-drying machine. The structure of the PMN chip consists of a substrate (8 mm in the width), the supporting posts (500 µm in diameter, 300 µm in height), and the needles (300 µm in length). The supporting post improves the penetration of the needle into the skin. The pitch between the centers of each needle is 1 mm. The pore size of the fabricated PMN was found to be about 10 µm from SEM images (Figure 1B). The mechanical strength evaluated by a force gauge and a load cell was 0.03 N/needle, which less than the enough strength to penetrate the skin (0.06 N/needle [3]). In order to improve the mechanical strength of the PLGA-PMNs, an aqueous solution of carboxymethyl cellulose (CMC) was filled in the pores of the PLGA-PMNs and dried. The CMC-filled PLGA-PMN showed a higher load-bearing capacity than the PLGA-PMN.By soaking the PMN with saline solution and applying current, the ionic conduction through the PLGA-PMN chip was observed. In addition, the water adsorbing rate of the CMC-filled PLGA-PMN was faster than that of PLGA-PMN. These results indicate the pores of the PMN form continuous channels through the chip, and the CMC improves wettability of the PLGA-PMN due to its high hydrophilicity. In conclusion, we successfully fabricated porous microneedle from biodegradable materials and improved the mechanical strength and hydrophilicity by stuffing the biodegradable polymer, which provides a key role for practical applications.

Mechanical characteristics and in vitro degradation kinetics analysis of polylactic glycolic acid/β-tricalcium phosphate (PLGA/β-TCP) biocomposite interference screw

The interference screw made of bioabsorbable polymers has been widely used in bone tissue engineering. Among the various ranges of polymer materials, the composite of polylactic glycolic acid (PLGA) and β-tricalcium phosphate (β-TCP) exerts high performance of biocompatibility and bioabsorption for the knee fixation and reconstruction surgery. The purpose of this research is to first investigate the influence of screw thread geometry on the mechanical properties of the biocomposites interference screw made of PLGA/β-TCP composite. Three biocomposite interference screws with different thread designs were compared in terms of the maximum insertion torque and pullout force via numerical analysis. It was found that the thread design with modified pitch failed to improve the ease of insertion into the bone tunnel and resistance of removal. Although the modified thread angle type enhanced the pull-out strength, the higher insertion torque and strain energy density (SED) exerted on the bone made it was easy to break during the insertion process and enlarge the bone tunnel. Then, based on the optimal design of the screw, in-vitro degradation experiment over 26 weeks was conducted to investigate the degradation kinetics and evaluate the mechanical properties of the PLGA/β-TCP interference screw. The in vitro degradation analysis revealed that the molecular weight residual rate and degradation time presented a linear negative correlation within 0 to 16 weeks and the degradation rate was significantly accelerated after 16 weeks. However, it didn't exhibit any differences in mass loss with the degradation time, which indicated that the material can still keep the shape in half a year. In other words, the interference screw made of PLGA/β-TCP composite can meet the requirements of clinical use and has a certain degree of safety.

Co-delivery of cisplatin and siRNA through hybrid nanocarrier platform for masking resistance to chemotherapy in lung cancer.

The resistance of cancer cells to chemotherapy has presented a formidable challenge. The current research aims at evaluating whether silencing of the cisplatin efflux promoter gene ABCC3 using siRNA co-loaded with the drug in a nanocarrier improves its efficacy in non-small cell lung cancer (NSCLC). Hybrid nanocarriers (HNCs) comprising lipids and poly(lactic acid-polyethylene glycol) di-block copolymer (PEG-PLA) were prepared for achieving the simultaneous delivery of cisplatin caprylate and ABCC3-siRNA to the cancer cells. PEGylation of the formulated HNCs was carried out using post-insertion technique for imparting long circulation characteristics to the carrier. The optimized formulation exhibited an entrapment efficiency of 71.9±2.2% and 95.83±0.39% for cisplatin caprylate and siRNA respectively. Further, the HNC was found to have hydrodynamic diameter of 153.2±1.76nm and +25.39±0.49mV zeta potential. Morphological evaluation using cryo transmission electron microscopy confirmed the presence of lipid bilayer surrounding the polymeric core in HNCs. The in vitro cellular uptake studies showed improved uptake, while cell viability studies of the co-loaded formulation in A549 cell-line indicated significantly improved cytotoxic potential when compared with drug solution and drug-loaded HNCs; cell cycle analysis indicated increased percentage of cell arrest in G2-M phase compared with drug-loaded HNCs. Further, the gene knock-down study showed that silencing of ABCC3 mRNA might be improved in vitro efficacy of the formulation. The optimized cisplatin and ABCC3 siRNA co-loaded formulation presented significantly increased half-life and tumour regression in A549 xenograft model in BALB/c nude mice. In conclusion, siRNA co-loaded formulation presented reduced drug resistance and increased efficacy, which might be promising for the current cisplatin-based treatments in NSCLC.

Chrysin nanocapsules with dual anti-glycemic and anti-hyperlipidemic effects: Chemometric optimization, physicochemical characterization and pharmacodynamic assessment

Chrysin is a flavonoid with various biological and therapeutic properties. However, its poor oral bioavailability and solubility are challenging barriers against its therapeutic use, which can be circumvented via encapsulation in a suitable nanocarrier. Therefore, the aim of this work was to prepare polymeric chrysin nanocapsules based on polylactic-glycolic acid PLGA with improved oral therapeutic potential, by optimization of their physicochemical properties using response surface methodology. Diabetes was induced in an animal model using streptozotocin to assess the anti-hyperglycemic activity of the selected formulation, and hyperlipidemia was induced in another animal model using a high fat diet to assess its anti-hyperlipidemic activity. Results revealed that the selected chrysin nanocapsular formulation exhibited particle size of 176 ± 2.10 nm, polydispersity index of 0.22 ± 0.01, negative zeta potential, drug entrapment efficiency of 87.10% ± 6.71, a controlled release of chrysin over a period of 24 h, and a significant physical stability after storage for 3 months. Compared to chrysin suspension, the selected nanocapsular formulation exhibited marked anti-hyperglycemic effect for up to 24 h, as well as superior anti-hyperlipidemic potential for 28 days. These improvements in chrysin therapeutic action after its encapsulation into polymeric nanocapsules delineate it as a promising remedy for oral treatment of diabetes and hyperlipidemia.

Validation of a UV-Spectrophotometric Method for Quantitative Determination of Paclitaxel in a Targeted Delivery System Based on Poly(Lactic–Glycolic Acid) Copolymer Nanoparticles

A UV spectrophotometric method for quantitative determination of paclitaxel in a conjugate of poly(lactic-glycolic acid) (PLGA) copolymer nanoparticles and a protein vector (recombinant third domain of alpha-fetoprotein) was developed. Paclitaxel was determined at wavelength 260 ± 2 nm. The proposed method showed specificity, linearity (R2 = 0.9948) in the range 80 – 120% of paclitaxel nominal load in the polymer matrix (0.18 mg/mL), accuracy, and precision. The developed method could be recommended for inclusion in regulatory documentation for quality control of paclitaxel nanoparticles conjugated with a protein vector.

Preparation and Characterization of PEG-PLA Genistein Micelles Using a Modified Emulsion-Evaporation Method

The objective of this study is to improve the bioavailability of genistein by encapsulation with polyethylene glycol-polylactic acid (PEG-PLA) copolymers. Genistein micelles (GMs) prepared using a modified emulsion-evaporation method were more stable than those made with the original method. The effect of polyvinyl alcohol, Tween 80, sonication time, PEG-PLA/genistein ratio, and organic phase (acetone)/H2O ratio on the size, polydispersity index, encapsulation efficiency, and drug loading efficiency of GMs was investigated. GMs were obtained and characterized under optimal experimental conditions. For long-term storage, GMs were lyophilized by freeze drying with trehalose to produce genistein lyophilized powder (GLP). The analysis of GLP by Fourier-transform infrared spectroscopy and differential scanning calorimetry showed that genistein was successfully incorporated into the micellar structure. In vitro release experiments revealed that the incorporation of genistein into PEG-PLA copolymers significantly improved its solubility and bioavailability. GLP was more potent in inhibiting the proliferation of HSC-T6 cells than genistein. Treatment with GLP at 10–20 μg/mL for 48 h significantly inhibited the protein expression of α-smooth muscle actin and collagen I in HSC-T6 cells compared with the control. These data demonstrated that the improved solubility and bioavailability of genistein in the form of GLP enhanced its antifibrotic effect in vitro.

Preparation of Temozolomide Nano SustainedRelease Microsphere Material and Its Application in Treatment of Glioma

The polylactic acid/glycolic acid (PLGA) sustained-release microspheres are used as the main material for local sustained-release in the study. Ultrasonic emulsification-solvent evaporation method is applied to combine the sustained-release microspheres material with temozolomide to form a composite sustained-release microsphere (TMZ-PLGA-W). The ratio of lactic acid (LA) and glycolic acid (GA) was adjusted so as to test the morphological characteristics of TMZ-PLGA-W at different ratios. The amount of drug released and the encapsulation rate of the material at different time periods were calculated. The C6 glioma system was implanted into the right caudate nucleus of Wistar rats to obtain a rat intracranial glioma model. The models were divided into 5 groups according to different sustained-release materials, and each group had 10 rats. The brain tumor at different times were compared and the survival time of rats was statistically calculated. The TMZ-PLGA-W sustained-release microsphere material with LA/GA ratio of 25%/75% was selected and placed in C6 cells culturing incubator according to different drug loadings. The cell activity according to the culture time was observed. The results showed that the TMZ-PLGA-W sustained-release microspheres prepared in the study were stable in structure, uniform in size, and free of cracks. At the same time, the sustained-release curve showed that the microsphere material conformed to the biodynamic law, which could reduce the burst effect and prolong the sustained release of the drug. The application of TMZ-PLGA-W sustained-release microspheres can effectively inhibit the increase in the area of brain tumors in rats, and at the same time improve the survival rate of rats. The increase in the drug loading of the microspheres can further inhibit the growth of glioma cells.

Evaluation of Collagen Membranes Coated with Testosterone and Alendronate to Improve Guided Bone Regeneration in Mandibular Bone Defects in Minipigs.

ABSTRACTObjectivesThe purpose of the present in vivo study was to evaluate whether pericard collagen membranes coated with ancillary amounts of testosterone and alendronate in a poly-lactic glycolic acid (PLGA) carrier as compared to uncoated membranes will improve early bone regeneration.Material and MethodsIn each of 16 minipigs, four standardized mandibular intraosseous defects were made bilaterally. The defects were filled with Bio-Oss® granules and covered with a non-coated or coated membrane. Membranes were spray-coated with 4 layers of PLGA containing testosterone and alendronate resulting in 20, 50 or 125 μg/cm2 of testosterone and 20 µg/cm2 alendronate (F20, F50, F125). Non-coated membranes served as controls (F0). Animals were sacrificed at 6 and 12 weeks after treatment. Qualitative and quantitative histological evaluations of bone regeneration were performed. Differences between groups were assessed by paired Student’s t‐test.ResultsLight microscopical analysis showed new bone formation that was in close contact with the Bio-Oss® surface without an intervening non-mineralized tissue layer. Histomorphometric analysis of newly formed bone showed a significant 20% increase in area in the F125 coated membrane treated defects (40 [SD 10]%) compared to the F0 treated defects after 6 weeks (33 [SD 10]%, P = 0.013). At week 12, the total percentage of new bone was increased compared to week 6, but no increase in newly formed bone compared to F0 was observed.ConclusionsThe data from this in vivo study indicate that F125 collagen membranes coated with testosterone and alendronate resulted in superior bone formation (+24%) when normalized to control sites using uncoated membranes.

Targeted delivery of protein binding polyethylene glycol-polylactic acid nanoparticles for the treatment of cerebral thrombosis

To study and analyze the suitability of protein binding polyethylene glycol-polylactic acid nanoparticles (PEGPLA-NPs) for the treatment of cerebral thrombosis, and its influence on platelet parameters. Patients with cerebral thrombosis admitted to our hospital from April 2017 to May 2018 were randomly divided into the control and observation groups. Data on the clinical history and blood parameters of the patients were compared. After treatment with the protein binding PEG-PLA-NPs, the plasma viscosity and whole blood viscosity of the observation group were significantly higher (p < 0.002) than those of the control group. The effective rate (93.3%) in the observation group was significantly higher than that of the control group (71.1%). The nanoparticles were characterized by high drug loading, high encapsulation efficiency, suitable preparation and purification methods, optimal particle size and shape, and controlled drug release. Protein binding PEG-PLA-NPs, therefore, could be suitable modalities for the treatment of cerebral thrombosis, and be effective in improving patient conditions and subsequent rehabilitation.

Study on preparation of 3D printing degradable tissue engineering ossicles

Objective: In combination with 3D printing technology and degradable composite materials, to discuss the preparation method of tissue engineering ossicles for middle ear hearing reconstruction. Methods: Domestic polymer (polylactic acid-glycolic acid copolymer, PLGA) and degradable ceramic material (β-tricalcium phosphate, β-TCP) were selected and prepared by low temperature deposition method according to the design ratio to Program according to the outline design code of the required scaffold to generate appropriate print files, and then the self-developed low-temperature deposition printing device was used to prepare tissue-engineered osseous scaffolds in accordance with the print files in a low-temperature environment. The scaffolds was freeze-dried and sterilized for later use after printing. Light microscopy and scanning electron microscopy were used to observe the apparent characteristics and internal structure of the scaffolds and to check its pore size, porosity and mechanical properties. Results: After printing, a degradable scaffold was obtained. Under the optical microscope, it was a small cylindrical shape with a diameter of 1.5 mm and a length of 6.0 mm, and its surface had micropores. The degradable scaffold had a horizontal and vertical interlaced warp and weft structure, the wire spacing was 1.2 mm, and the pores were connected to each other. The surface could see circular or quadrangular pores with a pore size of about 100-400 μm. The diameter of the inter-pore cross-linked channels was about 50 μm and the diameter of the surrounding circular micropores was about 10-40 μm. β-TCP particles with a size of about 700 nm were attached to the surface of the PLGA material. The average porosity of the whole scaffolds was (83.43±0.01)%, and the content of BMP-2 loaded was about 0.7 μg/mm(3). After freeze-drying, the mechanical strength of the scaffold was moderate, and there was no obvious deformation during stretching and compression, which met the mechanical requirements of tissue engineering ossicles. Conclusions: Using the low-temperature deposition printing method and strictly controlled processes and conditions, a polymer-degradable ceramic ossicle tissue engineering scaffold can be prepared for implantation experiments. The scaffold has suitable porosity and mechanical properties, and can be loaded with osteoinductive factors.

PLGA/PEO 블렌드의 수용성 및 기계적 특성에 미치는 사슬간 수소결합의 영향

Polyethylene oxide (PEO) possesses poor mechanical properties, which limits its application. For the purpose of improving the mechanical properties of water-soluble films, blend of polylactic glycolic acid (PLGA) with PEO was prepared by melt blending. The hydrogen bonding between PEO and PLGA was investigated by Fourier transform infrared spectrometer. The crystallization behavior, water solubility, and mechanical properties were evaluated. The results showed that there was a hydrogen bonding force between PLGA and PEO, and this force can improve the mechanical strength and water absorption of the film. When the PLGA content reached 20 wt%, the tensile strength and the elongation at break achieved a maximum 26.1MPa and 771.2%, respectively. Compared to neat PEO, blend with 10 wt% of PLGA had considerably higher water absorption capacity. When the PLGA content was 40 wt%, the film would not disperse in water.

Research on Gliding and Discharge Performance of Suspended Injection from Syringe —Effect of Diameter Ratio of Suspending Particle against Needle Hole on Needle Passageability—

Suspended injectable formulations such as sustained-release luteinizing hormone-releasing hormone (LH-RH) analogue loaded in polylactic acid-glycolic acid copolymer (PLGA) particles have been developed on market. Such formulations have potential issue of suspended particles blocking the injection needle. In this research, two types of injectability tests (gliding force, particles discharge) were developed to evaluate the needle passageability of suspended particles. The model suspension was newly designed using mono-dispersed polyethylene (PE) spheres and qualified dispersing fluid to enhance universality and validity of the test. The suspension-filled syringe, in which three sizes of spheres (L, M, S) were dispersed, was vertically fixed and pushed by auto-compression/tensile tester. The gliding force was continuously detected during testing time and all discharged PE spheres were collected and weighed. The combination of sphere (L, M, S) and injection needle were varied to evaluate the effect of the diameter ratio of sphere against needle hole (D/W) on passageability through needle. These injectability tests revealed that the blockage of a needle hole was occasionally observed when the D/W value increased up to 0.35-0.5, which was detected by jump-up of gliding force and drastic decrease of discharged sphere. In addition, the effect of the formulation properties (concentration of suspended spheres, viscosity of dispersing fluid) and operational factor (injection speed) on injectability was also investigated. The results from this study would be valuable in developing suspended injections and predicting injection trouble at the medical scene.

Rapid prototyping fabrication of soft and oriented polyester scaffolds for axonal guidance

Biodegradable polyesters have been extensively used for preparation of nerve guidance scaffolds, due to their high biocompatibility and defined degradation periods. However, conventional methods for fabrication of porous polyester scaffolds provide limited control over shape and micro-architecture. Here, a fabrication procedure based on 3D printing was developed to generate highly ordered and anatomically personalized, polyester scaffolds for soft tissue regeneration. Scaffolds composed of Poly-lactic-glycolic acid (PLGA) and poly-L-lactic acid (PLLA) were specifically customized for nerve injuries. This was obtained by using an oriented multi-layer printing pattern which established a linear structure in the fabricated scaffolds to match the aligned topography of nerve tissues. The oriented scaffold was shown to guide regenerating axons to linear conformations and support growth of induced pluripotent stem cell-derived neurons in vitro and in vivo in a model of spinal cord injury. The described scaffolds may advance the field of nerve regeneration. Furthermore, modifications could be integrated to generate soft implants for various types of tissues.

Design and in vitro characterization of multistage silicon-PLGA budesonide particles for inflammatory bowel disease

Inflammatory bowel disease (IBD) affects a confined area of the intestine and, therefore, administration of drugs via oral route is preferable. However, obstacles such as changes in the pH along gastrointestinal tract (GIT), enzymatic activity, and intraluminal pressure may cause low drug availability in the target tissue when delivered orally. Previous studies have pointed out the benefits of using micron-sized particles for targeting inflamed intestinal mucosa and nanoparticles for delivery of anti-inflammatory agents to the affected epithelial cells. We hypothesized that by combining the benefits of micro- and nano- particles, we could create a more efficient delivery system for budesonide, a glucocorticosteroid commonly used for anti-inflammatory IBD therapy. The aim of this study was to develop a novel multistage system for oral delivery designed to increase concentrations budesonidein the inflamed intestinal tissue. The multistage system consists of Stage 1 mesoporous silicon microparticles (S1MP) loaded with stage 2 poly-lactic-glycolic acid (PLGA) budesonide-encapsulating nanoparticles (BNP). BNP were efficiently loaded into S1MP (loading efficiency of 45.9 ± 14.8%) due to the large pore volume and high surface area of S1MP and exhibited controlled release profiles with enhanced drug dissolution rate in biologically relevant pHs. Due to the robustness in acidic pH and their geometry, S1MP protected the loaded budesonide in the acidic (gastric) pH with only 20% release. This allowed for the prolonged release of the BNP in the higher pH conditions (intestinal pH). The sustained release of BNP could facilitate accumulation in the inflamed tissue, enabling BNP to penetrate inflamed mucosa and release active budesonide to the target site. The multistage systems of S1MP and BNP were further evaluated in three-dimensional (3D) in vitro model of IBD and were found to (1) increase accumulation of BNP in the inflamed areas, (2) restore the barrier function of Caco-2 inflamed monolayer, and (3) significantly reduce pro-inflammatory cytokine release almost to the level of the healthy control.

Comparison of Aedes albopictus Monitoring Methods and Dengue Risk Assessment in Central China

Dengue fever has been attracting more attention in recent years. Dengue fever is mainly transmitted to humans by the Aedes albopictus mosquito and disease patterns are influenced by its wide distribution and high density during the summer season in China. Dengue epidemics in central China previously occurred exclusively in rural areas, while these recent outbreaks mostly occurred in urban areas in southern China. Until now, the presence of Aedes Albopictus in central China has been scarcely acknowledged. This study is a survey of Aedes and attempts to clarify this new distribution pattern using the Breteau Index (BI) method and a polylactic-glycolic acid (PLGA) copolymer mosquito trap simultaneously in urban and rural areas. The BI can provide a direct value on Aedes density compared to CI. Rural areas are at a higher risk for dengue compared to urban areas in central China. Our findings provide a basis for the prevention and control of dengue vectors, as well as providing information for control strategies for other infectious diseases transmitted by Aedes mosquitoes. Vector control strategy related to the management of diseases transmitted by Aedes should be based on the distribution patterns of different vector species, particularly in the rural environments in central China.

Therapeutic Arteriogenesis/Angiogenesis for Peripheral Arterial Disease by Nanoparticle-Mediated Delivery of Pitavastatin into Vascular Endothelial Cells

Two decades have passed since therapeutic angiogenesis was proposed to promote reparative collateral growth as an alternative therapy for ischemic diseases in patients for whom neither surgical revascularization nor endovascular therapy was suitable. When therapeutic angiogenesis first began, local administration was conducted using recombinant growth factor proteins or gene-encoding growth factors for endothelial cells. Since then, autologous stem cells and endothelial progenitor cell transplantation therapy have been developed. Although many clinical trials have been performed on patients, most therapies have not yet become standard treatments. We have developed a nanoparticle (NP)-mediated, drug-targeting delivery system using bioabsorbable poly-lactic/glycolic acid (PLGA) NPs. In several animal models, pitavastatin-incorporated (Pitava)-NPs showed significant therapeutic effects on critical limb ischemia. Because PLGA NPs are delivered selectively to vascular endothelial cells after intramuscular administration, it is suggested that therapeutic angiogenesis/arteriogenesis plays an important role in the mechanism by which Pitava-NPs exert beneficial therapeutic effects. To translate this to clinical medicine, we have performed studies and produced Pitava-NPs in compliance with good laboratory practice/good manufacturing practice regulations, and completed a phase I/II clinical trial, reporting the safety and efficacy of Pitava-NP intramuscular injection for patients with critical limb ischemia. This review will focus on therapeutic angiogenesis/arteriogenesis for peripheral arterial disease induced by Pitava-NPs.