Synthesis and characterization of semi-interpenetrating polymer network microspheres of acrylamide grafted dextran and chitosan for controlled release of acyclovir

Semi-interpenetrating polymer network (IPN) microspheres of acrylamide grafted on dextran (AAm-g-Dex) and chitosan (CS) were prepared by emulsion-crosslinking method using glutaraldehyde (GA) as a crosslinker. The grafting efficiency was found to be 94%. Acyclovir, an antiviral drug with limited water solubility, was successfully encapsulated into IPN microspheres by varying the ratio of AAm-g-Dex and CS, % drug loading and amount of GA. Microspheres were characterized by FT-IR spectroscopy to assess the formation of IPN structure and to confirm the absence of chemical interactions between drug, polymer and crosslinking agent. Particle size was measured using laser light scattering technique. Microspheres with average particle sizes in the range of 265–388 μm were obtained. Differential scanning calorimetry (DSC) and X-ray diffraction (X-RD) studies were performed to understand the crystalline nature of drug after encapsulation into IPN microspheres. Acyclovir encapsulation of up to 79.6% was achieved as measured by UV spectroscopy. Both equilibrium and dynamic swelling studies were performed in 0.1 N HCl. Diffusion coefficients (D) and diffusional exponents (n) for water transport were determined using an empirical equation. In vitro release studies indicated the dependence of drug release rates on both the extent of crosslinking and amount of AAm-g-Dex used in preparing microspheres; the slow release was extended up to 12 h. The release rates were fitted to an empirical equation to compute the diffusional exponent (n), which indicated non-Fickian trend for the release of acyclovir.     

Delivery of dermatan sulfate from polyelectrolyte complex-containing alginate composite microspheres for tissue regeneration

Dermatan sulfate (DS) is a glycosaminoglycan (GAG) with a great potential as a new therapeutic agent in tissue engineering. The aim of the present study was to investigate the formation of polyelectrolyte complexes (PECs) between chitosan and dermatan sulfate (CS/DS) and delivery of DS from PEC-containing alginate/chitosan/dermatan sulfate (Alg/CS/DS) microspheres for application in tissue regeneration. The CS/DS complexes were initially formed at different conditions including varying CS/DS ratio (positive/negative charge ratio), buffer, and pH. The obtained CS/DS complexes exhibited stronger electrostatic interaction, smaller complex size, and more stable colloidal structure when chitosan was in large excess (CS/DS 3:1) and prepared at pH 3.5 as compared to pH 5 using acetate buffer. The CS/DS complexes were subsequently incorporated into an alginate matrix by spray drying to form Alg/CS/DS composite microspheres with a DS encapsulation efficiency of 90-95%. The excessive CS induced a higher level of sustained DS release into Tris buffer (pH 7.4) from the microspheres formulated at pH 3.5; however, the amount of CS did not have a significant effect on the release from the microspheres formulated at pH 5. Significant cell proliferation was stimulated by the DS released from the microspheres in vitro. The present results provide a promising drug delivery strategy using PECs for sustained release of DS from microspheres intended for site-specific drug delivery and ultimately for use in tissue engineering.     

Novel interpenetrating polymer network microspheres of chitosan and methylcellulose for controlled release of theophylline

Interpenetrating polymer network (IPN) microspheres of chitosan (CS) and methylcellulose (MC) were prepared by emulsion-crosslinking in the presence of glutaraldehyde (GA) as a crosslinker. Theophylline (THP), an antiasthmatic drug was encapsulated into IPN microspheres under varying ratios of MC and CS, % drug loading and amount of GA added. IPNs have shown better mechanical properties than pure CS. Cross-link density of the matrices was significantly affected by the amount of GA and MC. Microspheres were characterized by Fourier transform infrared (FTIR) spectroscopy to assess the formation of IPN structure and to confirm the absence of chemical interactions between drug, polymer and crosslinking agent. Particle size was measured by laser light scattering technique. Microspheres with the average particle sizes ranging from 119 to 318 μm were produced. Differential scanning calorimetry (DSC) and X-ray diffraction (X-RD) studies were performed to understand the crystalline nature of drug after encapsulation into IPN microspheres. Theophylline encapsulation of up to 82% was achieved as measured by UV spectrometer. Equilibrium swelling was performed in distilled water. In vitro release studies were performed in both 0.1 N HCl and pH 7.4 buffer solutions. These data indicated a dependence of drug release on the extent of crosslinking and amount of MC added during the preparation of microspheres. The release was extended up to 12 h and release rates were fitted to an empirical equation to compute the diffusional parameters, which indicated a slight deviation from the Fickian trend for the release of theophylline.     

Interpenetrating polymer network (IPN) hydrogel microspheres for oral controlled release application

Interpenetrating polymer network (IPN) hydrogel microspheres of sodium carboxymethyl cellulose (NaCMC) and poly(vinyl alcohol) (PVA) were prepared by water-in-oil (w/o) emulsion crosslinking method for oral controlled release delivery of a non-steroidal anti-inflammatory drug, diclofenac sodium (DS). The microspheres were prepared with various ratios of NaCMC to PVA, % drug loading and extent of crosslinking density at a fixed polymer weight. The prepared microspheres with loose and rigid surfaces were evidenced by scanning electron microscope (SEM). Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis confirmed the IPN formation. Differential scanning calorimetry (DSC) study was performed to understand the dispersion nature of drug after encapsulation. The in vitro drug release study was extensively evaluated depending on the process variables in both acid and alkaline media. All the formulations exhibited satisfactory physicochemical and in vitro release characteristics. Release data indicated a non-Fickian trend of drug release from the formulations. Based on the results of this study suggest that DS loaded IPN microspheres were suitable for oral controlled release application.     

Utilization of drought-tolerant bacterial strains isolated from harsh soils as a plant growth-promoting rhizobacteria (PGPR)

Drought stress adversely affects plant health and productivity. Recently, drought-resistant bacterial isolates are used to combat drought resistance in crops. In this in vitro study, 20 bacterial isolates were isolated from harsh soil; their drought tolerance was evaluated using four concentrations of polyethylene glycol (PEG) 6000. The two most efficient isolates (DS4 and DS9) were selected and identified using 16S rRNA genetic sequencing. They were registered in the NCBI database and deposited under accession numbers MW916285 and MW916307 for Bacillus cereus (DS4) and Bacillus albus (DS9), respectively. These isolates were screened for plant growth-promoting properties compared to non-stressed conditions. Biochemical parameters; Proline, salicylic acid, gibberellic acid (GA), indole acetic acid (IAA), antioxidant activity, and antioxidant enzymes were measured under the same conditions, and in vitro seed germination was tested under stress conditions and inoculation with selected isolates. The results showed that under the harsh conditions of PEG6000, DS4 produced the highest amount of IAA of 1.61 µg/ml, followed by DS9 with 0.9 µg/ml. The highest amount of GA (49.95 µg/ml) was produced by DS9. On the other hand, the highest amount of siderophore was produced from DS4 isolate followed by DS9. Additionally, DS4 isolate recorded the highest exopolysaccharide (EPS) content of 3.4 mg/ml under PEG (-1.2 MPa) followed by DS9. The antioxidant activity increased in PEG concentrations depending manner, and the activity of the antioxidant enzymes increased, as catalase (CAT) recorded the highest activity in DS4 with an amount of 1.095 mg/ml. additionally, an increase in biofilm formation was observed under drought conditions. The isolated mixture protected the plant from the harmful effects of drought and showed an increase in the measured variables. Under unstressed conditions, the highest rates of emulsification index (EI 24%) were obtained for DS4 and DS9, at 14.92 and 11.54, respectively, and decreased under stress. The highest values of germination, total seedling length, and vigor index were obtained upon inoculation with the combination of two strains, and were 100%, 4.10 cm, and 410, respectively. Therefore, two strains combination is an effective vaccine capable of developing and improving drought tolerance in dryland plants.     

Novel pH- and Temperature-Responsive Blend Hydrogel Microspheres of Sodium Alginate and PNIPAAm-g-GG for Controlled Release of Isoniazid

This paper reports the preparation and characterization of novel pH- and thermo-responsive blend hydrogel microspheres of sodium alginate (NaAlg) and poly(N-isopropylacrylamide)(PNIPAAm)-grafted-guar gum (GG) i.e., PNIPAAm-g-GG by emulsion cross-linking method using glutaraldehyde (GA) as a cross-linker. Isoniazid (INZ) was chosen as the model antituberculosis drug to achieve encapsulation up to 62%. INZ has a plasma half-life of 1.5 h, whose release was extended up to 12 h. Fourier transform infrared spectroscopy was used to confirm the grafting reaction and chemical stability of INZ during the encapsulation. Differential scanning calorimetry was used to investigate the drug’s physical state, while powder X-ray diffraction confirmed the molecular level dispersion of INZ in the matrix. Scanning electron microscopy confirmed varying surface morphologies of the drug-loaded microspheres. Temperature- and pH-responsive nature of the blend hydrogel microspheres were investigated by equilibrium swelling, and in vitro release experiments were performed in pH 1.2 and pH 7.4 buffer media at 37°C as well as at 25°C. Kinetics of INZ release was analyzed by Ritger–Peppas empirical equation to compute the diffusional exponent parameter (n), whose value ranged between 0.27 and 0.58, indicating the release of INZ follows a diffusion swelling controlled release mechanism.KEY WORDS: blend hydrogel microsphere, graft copolymer, isoniazid, pH sensitive, temperature sensitive     

Coaxial Electrospray of Ranibizumab-Loaded Microparticles for Sustained Release of Anti-VEGF Therapies

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over age 65 in industrialized nations. Intravitreous injection of anti-VEGF (vascular endothelial growth factor) therapies, such as ranibizumab (trade name: Lucentis), provides an effective treatment option for neovascular AMD. We have developed an improved coaxial electrospray (CES) process to encapsulate ranibizumab in poly(lactic-co-glycolic) acid (PLGA) microparticles (MPs) for intravitreous injection and sustained drug release. This microencapsulation process is advantageous for maintaining the stability of the coaxial cone-jet configurations and producing drug-loaded MPs with as high as 70% encapsulation rate and minimal loss of bioactivitiy. The utility of this emerging process in intravitreous drug delivery has been demonstrated in both benchtop and in vivo experiments. The benchtop test simulates ocular drug release using PLGA MPs encapsulating a model drug. The in vivo experiment evaluates the inflammation and retinal cell death after intravitreal injection of the MPs in a chick model. The experimental results show that the drug-load MPs are able to facilitate sustained drug release for longer than one month. No significant long term microglia reaction or cell death is observed after intravitreal injection of 200 μg MPs. The present study demonstrates the technical feasibility of using the improved CES process to encapsulate water-soluble drugs at a high concentration for sustained release of anti-VEGF therapy.     

Functional Characterization of Two Cytochrome P450 Monooxygenase Genes, P450-1 and P450-4, of the Gibberellic Acid Gene Cluster in Fusarium proliferatum (Gibberella fujikuroi MP-D)

Gibberella fujikuroi is a species complex with at least nine different biological species, termed mating populations (MPs) A to I (MP-A to MP-I), known to produce many different secondary metabolites. So far, gibberellin (GA) production is restricted to Fusarium fujikuroi (G. fujikuroi MP-C), although at least five other MPs contain all biosynthetic genes. Here, we analyze the GA gene cluster and GA pathway in the closest related species, Fusarium proliferatum (MP-D), and demonstrate that the GA genes share a high degree of sequence homology with the corresponding genes of MP-C. The GA production capacity was restored after integration of the entire GA gene cluster from MP-C, indicating the existence of an active regulation system in F. proliferatum. The results further indicate that one reason for the loss of GA production is the accumulation of several mutations in the coding and 5′ noncoding regions of the ent-kaurene oxidase gene, P450-4.     

Synthesis and characterization of cross-linked malonylchitosan microspheres for controlled release of acyclovir

The purpose of the present study was to obtain a polymeric system for delayed release of the drug acyclovir (ACV), which can be used for treatment of Herpes simplex and Varicella Zoster. The gelled chitosan (GCT) microspheres were obtained by coacervation-phase separation. They were treated with malonic acid to obtain malonylchitosan (MLCT) microspheres, which were characterized by, Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (¹³C NMR), elemental analysis (CHN), thermogravimetric analysis (TG/DTG) and scanning electron microscopy (SEM). The drug was encapsulated in MLCT microspheres by a contact adsorption technique, and the final formulation (MLCT-ACV), was analyzed for loading efficiency, degree of swelling and in vitro release profiles. The results obtained support the N-substitution of malonyl groups in the MLCT microspheres. The loading efficiency increased with impregnation time and a major amount of drug was encapsulated after 24 h. The swelling rate was higher in acid pH. The median release time was 5.5 h in pH 1.2 and 6.8. The mechanism involved in release was non-Fickian (0.43 < n < 0.85, n = 0.8474) and Super Case II kinetics (n > 1, n = 1.0491) at pH 1.2 and 6.8, respectively.     

Fabrication of distilled water-soluble chitosan/alginate functional multilayer composite microspheres

Polysaccharides-based functional microspheres were fabricated under mild conditions. Firstly, magnetic alginate microspheres were prepared by emulsification/internal gelation and acted as substrates. Then the multilayer composite microspheres (MCM) were obtained through the layer-by-layer assembly of the distilled water-soluble chitosan and alginate. The components, morphology, and size distribution of the microspheres were characterized by element analysis (EA), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM) and laser particle size analyzer (LPSA). Both EA and XPS analysis results indicated that alternate immersion was an effective method for preparing MCM. Vibrating sample magnetometer, SEM and LPSA results showed that the microspheres had good dispersion, uniform particle size and were superparamagnetic. In addition, in vitro drug release behaviors of the microspheres were investigated by using hemoglobin (HB) and Coomassie brilliant blue G250 (CBB) as model drugs. It was found that the release rates of both HB and CBB from the composite microspheres were slower than those from the substrates.     

Investigation on Processing Variables for the Preparation of Fluconazole-Loaded Ethyl Cellulose Microspheres by Modified Multiple Emulsion Technique

Fluconazole-loaded ethyl cellulose microspheres were prepared by alginate facilitated (water-in-oil)-in-water emulsion technology and the effects of various processing variables on the properties of microspheres were investigated. Scanning electron microscopy revealed spherical nature and smooth surface morphology of the microspheres except those prepared at higher concentration of emulsifiers and higher stirring speeds. The size of microspheres varied between 228 and 592 μm, and as high as 80% drug entrapment efficiency was obtained depending upon the processing variables. When compared up to 2 h, the drug release in pH 1.2 HCl solution was slower than in pH 7.4 phosphate buffer saline solution. However, this trend was reversed at high shear conditions. The microspheres provided extended drug release in alkaline dissolution medium and the drug release was found to be controlled by Fickian-diffusion mechanism. However, the mechanism shifted to anomalous diffusion at high shear rates and emulsifier concentrations. The aging of microspheres did not influence the drug release kinetics. However, the physical interaction between drug and excipients affected the drug dissolution behaviors. X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC) analysis revealed amorphous nature of drug in the microspheres. Fourier transform infrared (FTIR) spectroscopy indicated stable character of fluconazole in the microspheres. The stability testing data also supported the stable nature of fluconazole in the microspheres. The fluconazole extracted from 80% drug-loaded formulation showed good in vitro antifungal activity against Candida albicans. Thus, proper control of the processing variables involved in this modified multiple emulsion technology could allow effective incorporation of slightly water soluble drugs into ethyl cellulose microspheres without affecting drug stability.     

The first report described as an important study: The association of mannose-binding lectin gene 2 polymorphisms in children with Down syndrome

BACKGROUND:

Mannose-binding lectin gene 2 (MBL2) plays a very important role in the first line of host immune response in Down syndrome (DS). The importance of MBL2 gene polymorphisms in children with DS is unclear, and no research has addressed MBL2 gene polymorphisms in patients with DS. This is the first report describing an important association between MBL2 gene polymorphisms and infections in children with DS.

MATERIALS AND METHODS:

We compared the frequency of single-nucleotide polymorphisms (SNPs) at two codons of the MBL2 gene in a cross sectional cohort of 166 children with DS and 229 controls. Polymorphisms at codons 54 (GGC→GAC) and 57 (GGA→GAA) in exon 1 of the MBL2 gene were typed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique using the restriction enzymes BshN1 (derivated from Bacillus sphaericus) and MboII (derivated from Moraxella bovis), respectively.

RESULTS:

MBL2 codon 54 GA genotype frequency was found to be lower in patients with DS (22.9%) than those of healthy controls (35.8%), differences were statistically significant (OR = 0.532, 95% CI = 0.339-0.836, P = 0.008). On the other hand, codon 57 polymorphism in the MBL2 gene was detected in none of the DS patients, but only one person in the control group showed codon 57 GA genotype (OR = 1.004, 95% CI = 0.996-1.013, P = 1.000).

CONCLUSION:

Our data provides an evidence for the first time that a homozygote or heterozygote for the variant, MBL2 alleles, is not associated with infections in patients with DS, and do not influence the incidence of infections.     

Preparation and characterization of glutaraldehyde cross-linked O-carboxymethylchitosan microspheres for controlled delivery of pazufloxacin mesilate

O-carboxymethylchitosan (OCMC) microspheres containing an antibiotic drug pazufloxacin mesilate (PM) have been successfully prepared by emulsion cross-linking using glutaraldehyde (GA). Various manufacturing parameters, including amount of cross-linking agent and OCMC:PM ratios were altered to optimize process variables during the microspheres production. The structure and morphology were characterized by Fourier transform infrared (FT-IR), wide-angle X-ray diffraction (WXRD) and scanning electron microscopy (SEM). The swelling and releasing behaviors of the microspheres at pH 1.2 and 7.4 media were investigated. The results revealed that the microspheres had a spherical, rough morphology and with a narrow size distribution. The degree of swelling of microspheres at pH 7.4 media was higher than that at pH 1.2 media. The microspheres proved to be successful in prolonging drug release. The release of PM was found to depend upon the extent of matrix cross-linking and drug loading. The release profiles of PM from OCMC microspheres were found to be biphasic with a burst release followed by a gradual release phase, and followed the Higuchi matrix model.     

Nose-To-Brain Delivery of PLGA-Diazepam Nanoparticles

The objective of the present investigation was to optimize diazepam (Dzp)-loaded poly(lactic-co-glycolic acid) nanoparticles (NP) to achieve delivery in the brain through intranasal administration. Dzp nanoparticles (DNP) were formulated by nanoprecipitation and optimized using Box-Behnken design. The influence of various independent process variables (polymer, surfactant, aqueous to organic (w/o) phase ratio, and drug) on resulting properties of DNP (z-average and drug entrapment) was investigated. Developed DNP showed z-average 148–337 d.nm, polydispersity index 0.04–0.45, drug entrapment 69–92%, and zeta potential in the range of −15 to −29.24 mV. Optimized DNP were further analyzed by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), ex-vivo drug release, and in-vitro cytotoxicity. Ex-vivo drug release study via sheep nasal mucosa from DNP showed a controlled release of 64.4% for 24 h. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay performed on Vero cell line showed less toxicity for DNP as compared to Dzp suspension (DS). Gamma scintigraphy and biodistribution study of DNP and DS was performed on Sprague-Dawley rats using technetium-99m-labeled (^99mTc) Dzp formulations to investigate the nose-to-brain drug delivery pathway. Brain/blood uptake ratios, drug targeting efficiency, and direct nose-to-brain transport were found to be 1.23–1.45, 258, and 61% for ^99mTc-DNP (i.n) compared to ^99mTc-DS (i.n) (0.38–1.06, 125, and 1%). Scintigraphy images showed uptake of Dzp from nose-to-brain, and this observation was in agreement with the biodistribution results. These results suggest that the developed poly(D,L-lactide-co-glycolide) (PLGA) NP could serve as a potential carrier of Dzp for nose-to-brain delivery in outpatient management of status epilepticus.KEY WORDS: controlled release, nanoparticles, process optimization, scintigraphy     

Improved Bioavailability of a Water-Insoluble Drug by Inhalation of Drug-Containing Maltosyl-β-Cyclodextrin Microspheres Using a Four-Fluid Nozzle Spray Drier

We previously developed a unique four-fluid nozzle spray drier that can produce water-soluble microspheres containing water-insoluble drug nanoparticles in one step without any common solvent between the water-insoluble drug and water-soluble carrier. In the present study, we focused on maltosyl-β-cyclodextrin (malt-β-CD) as a new water-soluble carrier and it was investigated whether drug/malt-β-CD microspheres could improve the bioavailability compared with our previously reported drug/mannitol (MAN) microspheres. The physicochemical properties of bare drug microparticles (ONO-2921, a model water-insoluble drug), drug/MAN microspheres, and drug/malt-β-CD microspheres were evaluated. In vitro aerosol performance, in vitro dissolution rate, and the blood concentration profiles after intratracheal administration were compared between these formulations. The mean diameter of both drug/MAN and drug/malt-β-CD microspheres was approximately 3–5 μm and both exhibited high aerosol performance (>20% in stages 2–7), but drug/malt-β-CD microspheres had superior release properties. Drug/malt-β-CD microspheres dissolved in an aqueous phase within 2 min, while drug/MAN microspheres failed to dissolve in 30 min. Inhalation of drug/malt-β-CD microspheres enhanced the area under the curve of the blood concentration curve by 15.9-fold than that of bare drug microparticles and by 6.1-fold than that of drug/MAN microspheres. Absolute bioavailability (pulmonary/intravenous route) of drug/malt-β-CD microspheres was also much higher (42%) than that of drug/MAN microspheres (6.9%). These results indicate that drug/malt-β-CD microspheres prepared by our four-fluid nozzle spray drier can improve drug solubility and pulmonary delivery.

Electronic supplementary material

The online version of this article (doi:10.1208/s12249-012-9826-z) contains supplementary material, which is available to authorized users.KEY WORDS: 4-fluid nozzle spray drier, inhalation therapy, maltosyl-β-cyclodextrin, microparticles, water-insoluble drug     

Multiunit Floating Drug Delivery System of Rosiglitazone Maleate: Development, Characterization, Statistical Optimization of Drug Release and In Vivo Evaluation

A multiunit floating drug delivery system of rosiglitazone maleate has been developed by encapsulating the drug into Eudragit® RS100 through nonaqueous emulsification/solvent evaporation method. The in vitro performances of microspheres were evaluated by yield (%), particle size analysis, drug entrapment efficiency, in vitro floating behavior, surface topography, drug–polymer compatibility, crystallinity of the drug in the microspheres, and drug release studies. In vitro release was optimized by a {3, 3} simplex lattice mixture design to achieve predetermined target release. The in vivo performance of the optimized formulation was evaluated in streptozotocin-induced diabetic rats. The results showed that floating microspheres could be successfully prepared with good yields (69–75%), high entrapment (78-97%), narrow size distribution, and desired target release with the help of statistical design of experiments from very small number of formulations. In vivo evaluation in albino rats suggested that floating microspheres of rosiglitazone could be a promising approach for better glycemic control.     

Circulating Microparticles and Coronary Plaque Components Assessed by Virtual Histology Intravascular Ultrasound of the Target Lesion in Patients with Stable Angina

High levels of microparticles (MPs) circulate in the blood of patients with atherosclerotic diseases where they can serve as potential biomarkers of vascular injury and cardiovascular outcome. We used virtual histology intravascular ultrasound (VH-IVUS) to evaluate the relationship between the levels of circulating MPs and the coronary plaque composition in patients with stable angina. We included 35 patients with stable angina (22 men, age 64 ± 9 years) and a de novo target lesion. Preintervention gray-scale and VH-IVUS analysis was performed across the target lesion. Volumetric analysis was performed over a 10-mm-long segment centered at the minimum luminal site. Blood samples were obtained from the femoral artery before coronary angioplasty. MPs were measured using a solid-phase capture assay from a commercial kit. We divided participants into either a low MPs group or high MPs group based on the median value of MPs. There was no significant difference in baseline characteristics between the groups. The plaque burden and remodeling index were similar between the groups. The presence of VH-IVUS-derived thin-cap fibroatheroma was not different between the groups. The percentage of the necrotic core (NC) was significantly higher in the high MPs group than in the low MPs group, both in planar (17.0 ± 8.8% vs. 24.1 ± 6.9%, p = 0.012) and volumetric analyses (17.0 ± 4.8% vs. 22.1 ± 4.3%, p = 0.002). Circulating MPs were positively correlated with the percentage of the NC area at the minimal luminal site (r = 0.491, p = 0.003) and the percentage of the NC volume (r = 0.496, p = 0.002). Elevated levels of circulating MPs were associated with the amount of NC in the target lesion in those with stable angina, suggesting a potential role of circulating MPs as a biomarker for detecting unstable plaque in patients with stable angina.     

Sustained release of isoniazid from polylactide microspheres prepared using solid/oil drug loading method for tuberculosis treatment

Polylactide(PLA) microspheres were prepared using the solid-in-oil(S/O) spray-drying method to achieve the sustained release of a hydrophilic drug for the treatment of tuberculosis, via intratracheal instillation. Isoniazid(IN), a low-molecular-weight hydrophilic drug, was used as a model drug. The effects of various sizes of micronized IN powder, different drug/polymer ratios, spray-drying process parameters, and drug-release characteristics were studied to optimize the manufacturing parameters. A high entrapment efficiency(87.3%) was obtained using this method; furthermore, the microspheres were spherical and smooth. They were individually and homogenously distributed, with a mean diameter of 5.6 μm; furthermore, they showed a satisfactory extended sustained-release phase. After administration of the microspheres to rats, pulmonary drug concentrations were maintained at a relatively stable level for up to 4 weeks.     

Fabrication of novel magnetic nanoparticles-coated P(styrene-itaconic acid-divinylbenzene) microspheres

In this paper, P(styrene-itaconic acid-divinylbenzene) microspheres (P(St-IA-DVB) microspheres) based on styrene (St), itaconic acid (IA) and divinylbenzene (DVB) were prepared via water-in-oil emulsions method (W/O) in the presence of emulsifiers with the size of 5-10 μm. The magnetic nanoparticles (i.e. Fe₃O₄) coated tightly on the surface of P(St-IA-DVB) microspheres were prepared in water with a continuous stirring. The morphology of blank microspheres and magnetic nanoparticles-coated microspheres was investigated in this work. In vitro drug release behavior was studied using doxorubicin as a model drug, and these magnetic nanoparticles-coated P(St-IA-DVB) (MNPSID) microspheres might have great potential application in magnetically targeted and thermal therapy.     

Rapid homogeneous lauroylation of wheat straw hemicelluloses under mild conditions

Hemicellulose-based hydrophobic biomaterials with degrees of substitution ranging from 0.46 to 1.54 were synthesized under mild conditions in homogeneous media (N,N-dimethylformamide-lithium chloride) by reacting the native wheat straw hemicellulosic polymers with lauroyl chloride using 4-dimethylaminopyridine as a catalyst. Other catalysts such as N-bromosuccinimide, N-methyl pyrrolidine, N-methyl pyrrolidinone, and pyridine were also investigated. Under optimum reaction conditions (2 equiv of lauroyl chloride and triethylamine per hydroxyl group, 5% 4-dimethylaminopyridine, 40 °C, 35 min), a high DS value of 1.54 was obtained. The biomaterials were characterized by FT-IR spectroscopy and ¹³C NMR spectroscopy as well as by thermal analysis. The results showed that the lauroylation occurred preferably at the C-3 hydroxyl group of β-d-Xylp units in the hemicelluloses, and the thermal stability of the hydrophobic polymers increased by esterification.