Nerve growth factor-basic fibroblast growth factor poly-lactide co-glycolid sustained-release microspheres and the small gap sleeve bridging technique to repair peripheral nerve injury

We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.

Magnetic core-shell microparticles for oil removing with thermal driving regeneration property

Here, we report the construction of magnetic core-shell microparticles for oil removal with thermal driving regeneration property. Water-in-oil-in water (W/O/W) emulsions from microfluidics are used as templates to prepare core-shell microparticles with magnetic holed poly (ethoxylated trimethylolpropane triacrylate) (PETPTA) shells each containing a thermal-sensitive poly (N-Isopropylacrylamide) (PNIPAM) core. The microparticles could adsorb oil from water due to the special structure and be collected with a magnetic field. Then, the oil-filled microparticles would be regenerated by thermal stimulus, in which the inner PNIPAM microgels work as thermal-sensitive pistons to force out the adsorbed oil. At the same time, the adsorbed oil would be recycled by distillation. Furthermore, the adsorption capacity of the microparticles for oil keeps very stable after 1st cycle. The adsorption and regeneration performances of the microparticles are greatly affected by the size of the holes on the outer PETPTA shells, which could be precisely controlled by regulating the interfacial forces in W/O/W emulsion templates. The optimized core-shell microparticles show excellent oil adsorption and thermal driving regeneration performances nearly without secondary pollution, and would be a reliable green adsorption material for kinds of oil.

Research into Antibacterial Effects of Polysaccharide-Based Microparticles

Background: Due to worldwide increases in the prevalence of antibiotic-resistant bacteria, it is necessary to develop an active drug delivery system that can enable therapeutics to reach their molecular targets. Maintaining the concentration of any drug in the blood at a certain level for a long time is critical in the practice of drug therapy. With the increased frequency of drug use, the blood concentration of drugs exceeds the therapeutic level, leading to toxicity or ineffectiveness. To solve these problems, in recent years, much attention has been given to developing micro/nano preparations by encapsulating biologically active compounds on polymeric carriers. Therefore, we aimed to extract pectin from sea buckthorn peel, prepare microcapsules containing antibiotics, and determine their physical and chemical properties. Methods: Wastes were separated from sea buckthorn under “Medical raw materials Dry fruit of Hippophae rhamnoides MNS 5225:2002”. Pectin was isolated from sea buckthorn waste according to the “method for determination of pectins MNS3080:1981” standard. The degree of esterification was determined according to ISO 7623:2016. Antibiotic encapsulation with coacervates and water-based emulsions was performed. Antibiotic sensitivity was determined by microdilution according to the Clinical Laboratory Standard Institute (МТ100-S27) method. The results were determined between standard strains of Staphylococcus aureus ATCC 29213 and MRSA ATCC 2758 at different dilution concentrations. Result: Pectin is a brown powder with a sour taste and no odor. There was 71.4% esterification of pectin, 8.9% yield, 1.3% free carboxyl group, 3.2% methylated carboxyl group, 4.5% total carboxyl group, 3.5% ash, and 0.1% nitrogen. A study of the antibacterial activity of pectin containing doxycycline hyclate found that the inhibition of bacterial growth was 0.8 times less than that of pure pectin. It was 1 time less than that of doxycycline alone, and 33 times smaller than that of wontaxime when compared to pure pectin. Pectin containing doxycycline hyclate inhibited MRSA growth at a concentration 6 times lower than pure pectin. This was 2 times lower than doxycycline alone, and 8 times lower than wontaxime. Conclusion: Pectin yields 1.3 after 60 minutes of separation at a sediment concentration ratio of 1:1.15 and pH = 2. Pectin itself is antibacterial against MRSA.

Combustion Characteristics of Solid Sustained-Release Energetic Materials

A solid sustained-release energetic material sample,an eruption device and a complete test system were prepared further to analyse the combustion characteristics of solid sustainedrelease energetic materials.The high-temperature heat flux generated by the combustion of the samples from the eruption device was used to penetrate the Q235 target plate.In addition,the meaning and calculation formula of energy density characterising the all-around performance of heat flux were proposed.The numerical simulation of the combustion effect of samples was carried out.According to the data comparison,the numerical simulation results agreed with the experimental results,and the maximum deviation between the two was less than 8.9%.In addition,the structure of the combustion wave and high-temperature jet was proposed and analysed.Based on theoretical analysis,experimental research and numerical simulation,the theoretical burning rate formula of the sample was established.The maximum error between the theoretically calculated mass burning rate and the experimental results was less than 9.8%.Therefore,using the gas-phase steady-state combustion model to study the combustion characteristics of solid sustained-release energetic materials was reasonable.The theoretical burning rate formula also had high accuracy.Therefore,the model could provide scientific and academic guidance for the theoretical research,system design and practical application of solid sustained-release energetic materials in related fields.

A Novel Facial Cream Based on Skin Penetrable Hemp Oil Microparticles

Objective: Hemp seed oil is perfect for most skin types;it moisturizes skin and protects it from inflammation, oxidation, and other causes of aging. The problem is that the Hemp oil-based products do not penetrate the skin;they remain on the skin’s surface. Recently researchers have been trying to prepare nano emulsions of hemp oil to facilitate its permeation to deep skin layers. In all techniques used today, surfactants are added to the emulsification process. These surfactants may cause unwanted skin side effects. In the present study, we prepare micronized Hemp (m-Hemp) without using any surfactants in the micronization process, thus avoiding the side effects associated with surfactant addition. Methods & Results: Particles size of m-Hemp was evaluated using electron microscopy. Various sizes of m-Hemp were found, the smallest being 100 nm in diameter. The antioxidation properties of m-Hemp were measured using the Electron Spin Resonance (ESR) technique and were found to be enhanced. Skin topography and morphology following a cream containing m-Hemp treatment were visualized by Optical Profilometry and ESEM respectively. The results show a marked improvement in skin topography in all measured parameters. In addition, human keratinocytes (HaCaT) were exposed to inflammatory conditions and were then treated using Hemp. As a result, one of the key inflammatory factors (IL-2) was significantly reduced after treatment with m-Hemp (p ≤ 0.0001). The skin penetration of the cream containing m-Hemp was tested on human skin using the IMOPE (Iterative Multi-plane Optical Property Extraction) system. The results indicate that m-Hemp penetrates both the stratum corneum and the deep epidermal layers towards the dermis. Conclusion: The new cream prepared with micronized Hemp shows significant anti-inflammatory and antioxidative effects and demonstrates the entrance of m-Hemp to the skin epidermal layer.

Pharmacokinetics of nifedipine sustained-release tablets in healthy Chinese volunteers

Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4.6 mm ×150 mm） column and a mobile phase of methanol： 0.01 mol·L^-1ammonium acetate （60：40, V/V） were used to separate nifedipine, the detections was accuracy under atmosperic pressure electronic spray ionization （AP-ESI） mode and ion mass spectrum （m/z） of 314.9 [M＋H]^＋ for nifedipine, and 320.8 [M＋H]^＋ for lorazepam （Internal Standard, IS）. Results The linear range of nifedipine was 0.3 - 80 ng·mL^-1 （ r = 0.9997）, and the limit of quantitation （LOQ） was 0.3 ng·mL^-1. The nifedipine pharmacokinetic parameters after a single dose of 20 mg nifedipine sustained-release tablets test （T） or reference （R） were as the followings, t1/2 （6.73 ± 2.00） h and （7.04 ± 2.18） h, Tmax （4.28 ± 0.70） h and （4.48 ± 0.70） h, Cmax（39.66 ± 10.58） ng·mL^-1 and （40.19 ± 10.97） ng·mL^-1, AUC0-36 （391.63 ± 108.55） ng·mL^-1·h and （387.57 ± 121.51） ng·mL^-1·h, and AUC0-∞ （408.28 ± 121.16） ng·mL^-1·h and （406.15 ± 133.13） ng·mL^-1·h. The relative bioavailability of nifedipine sustained-release tablets （test） was （103.02 ± 13.93） %. Conclusion LC-MS method for the determination of concentrations of nifedipine in human plasma was sensitive and accurate, and could be used in nifedipine bioavailability and pharmacokinetic studies.

Preparation of Sustained-release Silybin Microspheres by Spherical Crystallization Technique

Aim To improve the dissolution rate and bioavailability of silybin. Methods Sustained-release silybin microspheres were prepared by the spherical crystallization technique with soliddispersing and release-retarding polymers. A differential scanning calorimeter and an X-ray diffractometer were used to investigate the dispersion state of silybin in the microspheres. The shape, surface morphology, and internal structure of the microspheres were observed using a scanning electron microscope. Characterization of the microspheres, such as average diameter, size distribution and bulk density of the microspheres was investigated. Results The particle size of the microspheres was determined mainly by the agitation speed. The dissolution rate of silybin from microspheres was enhanced by increasing the amount of the dispersing agents, and sustained by the retarding agents. The release rate of microspheres was controlled by adjusting the combination ratio of the dispersing agents to the retarding agents. The resuits of X-ray diffraction and differential scanning calorimetry analysis indicated that silybin was highly dispersed in the microspheres in amorphous state. The release profiles and content did not change after a three-month accelerated stability test at 40 ℃ and 75% relative humidity. Conclusion Sustained-release silybin microspheres with a solid dispersion structure were prepared successfully in one step by a spherical crystallization technique combined with solid dispersion technique. The preparation process is simple, reproducible and inexpensive. The method is efficient for designing sustained-release microspheres with water-insoluble drugs.

Pharmacokinetics and Relative Bioavailability ofsustained-release Tablets of Diclofenac Sodiumin Male Volunteers

The pharmacokinetics of a sustained- release formulation and an enteric- coated tablet of diclofenac sodium were studied on 8 healthy male volunteers in an open,randomized crossover study.Drug level in serum was assayed by HPLC method.The changes in serum concentration were conformed to a l-compartment open model.The t_1/2 (Ke)averaged 2.15±0.17 and ll.60 ± l.95 h,and the areas under the drug concentration curves were 5.87 ± 0.67 and 5.55 ± 0.57μgh/ml for enteric-coated and sustained-release tablet of diclofenac sodium,respectively. The mean relative bioavailability of sustained-release tablet was 0.95 to that of enteric-coated tablet.

Comparison of chemiluminescence enzyme immunoassay based on magnetic microparticles with traditional colorimetric ELISA for the detection of serum α-fetoprotein

A chemiluminescence enzyme immunoassay based on magnetic microparticles (MmPs-CLEIA) was developed to evaluate serum a-fetoprotein (AFP) in parallel with traditional colorimetric enzyme-linked immunosorbent assay (ELISA).A systematic comparison between the MmPs-CLEIA and colorimetric ELISA concluded that the MPs-CLEIA exhibited fewer dosages of immunoreagents,less total assay time,and better linearity,recovery,precision,sensitivity and validity.AFP was detected in forty human serum samples by the proposed MPs-CLEIA and ELISA,and the results were compared with commercial electrochemiluminescence immunoassay (ECLIA) kit.The correlation coefficient between MPs-CLEIA and ELISA was obtained with R 2 0.6703;however,the correlation between MPs-CLEIA and ECLIA (R 2 0.9582) was obviously better than that between colorimetric ELISA and ECLIA (R 2 0.6866).

Seasonal and Spatial Variability of Microparticles in Snowpits on the Tibetan Plateau, China

The work presents microparticle concentrations in snowpits from the East Rongbuk Glacier on Mt. Qomolangma (Everest) (ER) (28.02°N, 86.96°E, 6536 m a.s.l.), the Zhadang Glacier on Mt. Nyainqentanglha (NQ) (30.47°N, 90.65°E, 5800m a.s.l.), and the Guoqu Glacier on Mt. Geladaindong (GL) (33.95°N, 91.28°E, 5823m a.s.l.) over the Tibetan Plateau (TP). Variations of microparticle and major ions (e.g. Mg2+, Ca2+) concentrations in snowpits show that the values of the microparticles and ions in the non-monsoon seasons are much higher than those in the monsoon seasons. Annual flux of microparticle deposition at ER is lower than those at NQ and GL, which could be attributed to the long distance away from the possible dust source regions as well as the elevation for ER higher than the others. Compared with other remote areas, microparticle concentrations in the southern TP are much lower than those in the northern TP, but still much higher than those in Greenland and Antarctica. The seasonal and spatial microparticle variations are clearly related to the variations of atmospheric circulation according to the air mass 5-day backward trajectory analyses of HYSPLIT Model. Resultingly, the high microparticle values in snow are mainly attributed to the westerlies and the strong dust storm outbreaks on the TP, while the monsoon circulation brings great amount of precipitation from the Indian Ocean, thus reducing in the aerosol concentrations.

Preparation of Thermosensitive Chitosan Formulations Containing 5-Fluorouracil/Poly-3-hydroxybutyrate Microparticles Used as Injectable Drug Delivery System

The auto-gelling and drug release properties of the thermosensitive chitosan-β-glycerophosphate formulation were investigated. According to rheological study, gelation lag time of chitosan/β-glycerophosphate （GP） solutions varied from 2 to 60min with different deacetylation degree of chitosan, pH, gelation temperature, and the particles in the sol. The gelation properties were also found to influence the release profilles of a hydrophilic drug, 5-fluorouracil （5-FU）. Morphological examination by scanning electron microphotography demonstrated that large ＂pores＂ occurred during the gel-forming process, which created hydrophilic environment and led to the rapid initial release of the drug （85% in f＇LrSt 8h）. Poly-3-hydroxybutyrate （PHB）, a biodegradable material, was applied here as scaffold to capture 5-FU into microparticles with high encapsulation efficiency by solvent-nonsolvent method. Combination of these microparticles into the chitosan-β-GP formulation could drop the rapid initial release from 85% down to 29% in the optimized PHB content （75%, by mass）. The release could sustain for about 10 months. Tiffs study provided an understanding of the potential of injectable implant using thermosensitive chitosan-β-GP formulation containing PHB based particles for the water soluble drugs that need the property of long-term delivery.

Synthesis of Iron-containing Carbon Microparticles from Deoiled Asphalt and Ferrocene

The deoiled asphalt as the carbon source and the ferrocene as the metal source and the catalyst precursor were chosen to synthesize iron-containing carbon microparticles through co-carbonization at the temperature of about 450℃ for 3 h. The resulting products were treated at 2 000 ℃ for 2 h. All samples were examined by high resolution transmission electron microscopy （HRTEM） and X-ray diffraction （XRD）. The results show that the iron particles in the heat-treated material are completely coated by carbon. In addition to the fully filled carbon microparticles as well as hollow carbon ones, also form carbon fibers with hollow centers. The formation mechanism of the as-prepared products was discussed briefly.

Role of microparticles in endothelial dysfunction and arterial hypertension

Microparticles are small cell vesicles that can be released by almost all eukaryotic cells during cellular stress and cell activation. Within the last 1-2 decades it has been shown that microparticles are useful blood surrogate markers for different pathological conditions, such as vascular inflammation, coagulation and tumour diseases. Several studies have investigated the abundance of microparticles of different cellular origins in multiple cardiovascular diseases. It thereby has been shown that microparticles released by platelets, leukocytes and endothelial cells can be found in conditions of endothelial dysfunction, acute and chronic vascular inflammation and hypercoagulation. In addition to their function as surrogate markers, several studies indicate that circulating microparticles can fuse with distinct target cells, such as endothelial cells or leukocyte, and thereby deliver cellular components of their parental cells to the target cells. Hence, microparticles are a novel entity of circulating, paracrine, biological vectors which can influence the phenotype, the function and presumably even the transcriptome of their target cells.This review article aims to give a brief overview about the microparticle biology with a focus on endothelial activation and arterial hypertension. More detailed information about the role of microparticles in pathophysiology and disease can be found in already published work.

Supercritical Antisolvent Precipitation of Microparticles of Quercetin

Supercritical antisolvent (SAS) process is a recently developed technology to produce micro- and nano particles. This paper presents a continuous apparatus to conduct experiment of SAS process. With the apparatus, the effects of pressure, temperature and flow ratio of CO2 to the solution on the shape and size of particles are studied for the quercetin-ethanol-CO2 system. Spherical quercetin microparticles with diameters ranging form 1 μm to 6μm can be obtained while ethanol is used as organic solvent. The most effective fact on the shape and size of particles is pressure, the next is temperature and the last is the flow ratio of CO2 to solution.

Dynamics of circulating microparticles in chronic kidney disease and transplantation:Is it really reliable marker?

The deterioration of endothelial structure plays a very important role in the development of vascular diseases. It is believed that endothelial dysfunction starts in the early stage of kidney disease and is a risk factor of an unfavorable cardiovascular prognosis. Because a direct assessment of biological states in endothelial cells is not applicable, the measurement of endothelial microparticles(EMPs) detached from endothelium during activation or apoptosis is thought to be a marker of early vascular disease and endothelial dysfunction in children with chronic kidney disease(CKD). Few studies have shown increased circulating EMPs and its relationship with cardiovascular risk factors in patients with CKD.MPs contain membrane proteins and cytosolic material derived from the cell from which they originate. EMPs having CD144, CD 146, CD31+/CD41-, CD51 and CD105 may be used to evaluate the vascular endothelial cell damage and determine asymptomatic patients who might be at higher risk of developing cardiovascular disease in CKD and renal transplant.

Biocompatibility of Porous Spherical Calcium Carbonate Microparticles on Hela Cells

Recently there has been a wide concern on inorganic nanoparticles as drug delivery carriers. CaCO3 particles have shown promising potential for the development of carriers for drugs, but little research had been performed regarding their safe dosage for maximizing the therapeutic activity without harming biosystems. In this study, we assessed the biological safety of porous spherical CaCO3 microparticles on Hela cells. The reactive oxygen species (ROS), glutathione (GSH), carbonyl content in proteins (CCP), DNA-protein crosslinks (DPC) and cell viability were measured. Results showed that with the exposure concentration increase, ROS and CCP in Hela cells presented a significant increase but GSH contents in Hela cells and cell viability showed a significant decrease respectively compared with the control. DPC coefficient ascended, but no statistically significant changes were observed. The results indicated that porous spherical CaCO3 microparticles may induce oxidative damage to Hela cells. But compared with other nanomaterials, porous spherical CaCO3 appeared to have good biocompatibility. The results implied that porous spherical calcium carbonate microparticles could be applied as relatively safe drug vehicles, but with the caveat that the effect of high dosages should not be ignored when attempting to maximize therapeutic activity by increasing the concentration.

Methylprednisolone microsphere sustained-release membrane inhibits scar formation at the site of peripheral nerve lesion

Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thickness of the myelin sheath. Our findings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration.

Properties of Aroma Sustained-release Cotton Fabric with Rose Fragrance Nanocapsule

The aroma sustained-release cotton fabric was prepared by finishing rose fragrance nanocapsules directly on cotton.The structure and properties of nanocapsules were demonstrated by transmission electron microscope(TEM),dynamic light scattering(DLS),fourier transform infrared spectrometer(FTIR),X-ray diffraction (XRD),gas chromatography-mass spectrometry(GC-MS)and electronic nose.The results showed that the spherical nanocapsule dispersed evenly and the average diameter kept 51.4 nm.The existence of COO peak(1741 cm? 1)in the FTIR curve of the finished cotton fabric and the decrease of crystallinity demonstrated that rose fragrance nanocapsules have been incorporated into the cotton fabrics.The washing resistance of the cotton fabrics finished by 51.4 nm nanocapsules was much better than that by rose fragrance alone.Besides,the loss of fragrance from the cotton fabrics finished by 51.4 nm nanocapsules was obviously lower than that by 532 nm nanocapsules and rose fragrance.The smaller the nanocapsule size,the better the sustained release property.Electronic nose analysis also displayed that the aroma released from the cotton fabrics finished by nanocapsules after washing has no obvious variety in contrast to that without washing.The cotton fabrics finished by nanocapsules has the excellent sustained release property.

Subchronic Oral Toxicity of Silica Nanoparticles and Silica Microparticles in Rats

Objective To investigate the subchronic oral toxicity of silica nanoparticles（NPs） and silica microparticles（MPs） in rats and to compare the difference in toxicity between two particle sizes.Methods Sprague-Dawley rats were randomly divided into seven groups： the control group; the silica NPs low-, middle-, and high-dose groups; and the silica MPs low-, middle-, and high-dose groups [166.7,500, and 1,500 mg/（kg·bw·day）]. All rats were gavaged daily for 90 days, and deionized water was administered to the control group. Clinical observations were made daily, and body weights and food consumption were determined weekly. Blood samples were collected on day 91 for measurement of hematology and clinical biochemistry. Animals were euthanized for necropsy, and selected organs were weighed and fixed for histological examination. The tissue distribution of silicon in the blood, liver,kidneys, and testis were determined.Results There were no toxicologically significant changes in mortality, clinical signs, body weight,food consumption, necropsy findings, and organ weights. Differences between the silica groups and the control group in some hematological and clinical biochemical values and histopathological findings were not considered treatment related. The tissue distribution of silicon was comparable across all groups.Conclusion Our study demonstrated that neither silica NPs nor silica MPs induced toxicological effects after subchronic oral exposure in rats.

Preparation and Crystal Modification of Ibuprofen-Loaded Solid Lipid Microparticles

An emulsion-congealing technique is used to prepare solid lipid microparticles （SLM） containing ibuprofen with glyceryl behenate, tripalmitin and beewax as excipients. The difference of the solubility parameters between the excipients and ibuprofen are used to analyze their compatibility. Both the solubility parameter analysis and the experimental results show that glyceryl behenate is the best among the three excipients. The solid particles disperse well in aqueous phase when the drug loading reaches 10% （relative to lipid only）. Glycerides exhibit marked polymorphism and their rapid rates of crystallization accelerate the formation of metastable crystal modification. The metastable crystal modification characterizes high drug loading capacity but less stability. Increasing the content of lipophilic drug in a lipid matrix facilitates the transformation of excipients to more stable polymorphic forms.