Development and in vitro characterization of chitosan-coated polymeric nanoparticles for oral delivery and sustained release of the immunosuppressant drug mycophenolate mofetil

Objective: To develop an oral sustained release formulation of mycophenolate mofetil (MMF) for once-daily dosing, using chitosan-coated polylactic acid (PLA) or poly(lactic-co-glycolic) acid (PLGA) nanoparticles. The role of polymer molecular weight (MW) and drug to polymer ratio in encapsulation efficiency (EE) and release from the nanoparticles was explored in vitro.

Methods: Nanoparticles were prepared by a single emulsion solvent evaporation method where MMF was encapsulated with PLGA or PLA at various polymer MW and drug: polymer ratios. Subsequently, chitosan was added to create coated cationic particles, also at several chitosan MW grades and drug: polymer ratios. All the formulations were evaluated for mean diameter and polydispersity, EE as well as in vitro drug release. Differential scanning calorimetry (DSC), surface morphology, and in vitro mucin binding of the nanoparticles were performed for further characterization.

Results: Two lead formulations comprise MMF: high MW, PLA: medium MW chitosan 1:7:7 (w/w/w), and MMF: high MW, PLGA: high MW chitosan 1:7:7 (w/w/w), which had high EE (94.34% and 75.44%, respectively) and sustained drug release over 12?h with a minimal burst phase. DSC experiments revealed an amorphous form of MMF in the nanoparticle formulations. The surface morphology of the MMF NP showed spherical nanoparticles with minimal visible porosity. The potential for mucoadhesiveness was assessed by changes in zeta potential after incubation of the nanoparticles in mucin.

Conclusion: Two chitosan-coated nanoparticles formulations of MMF had high EE and a desirable sustained drug release profile in the effort to design a once-daily dosage form for MMF.     

Mangosteen peel and seed as antimicrobial and drug delivery in rubber products

Garcinia mangostana Linn. or mangosteen is a tropical superfruit with an excellent taste. The peel and seed of mangosteen waste can be used in medical, cosmetic, and health-care applications. Both mangosteen peel and seed have outstanding antibiotic properties and are suitable for use as bio-fillers in natural rubber latex products such as medical gloves, rubber transdermal patches, rubber toys, and rubber-health care products. In addition, mangosteen seed composed of griseofulvin polyethylene glycol [(C₂H₄O₂)_n]_1-x (C₁₇H₁₇ClO₆)_x is useful for treating osteoarthritis of the knee, similar to commercial glucosamine (amino sugar). Adding mangosteen peel and mangosteen seed in rubber gloves and rubber patches, respectively, is an alternative form of antimicrobial and drug delivery replacing taking a tablet. This study compared the characteristics and properties of mangosteen peel with silver nitrate (AgNO₃) and compared the characteristics and properties of mangosteen seed with commercial glucosamine using the film casting dipping process. The obtained natural rubber latex gloves with added mangosteen peel powder had a good appearance with a high contact angle (resulting in hydrophobicity and low wettability with water equal to 130.67° ± 2.08°), good mechanical properties (high percentage of elongation at break 815.72 ± 54.67%, high tensile strength 64.59 ± 13.54 MPa, good stiffness 296.50 ± 48.32 N/m, and high Young's modulus 29.65 ± 4.83 MPa), and as it was non-toxic to skin it was suitable for application in medical gloves and transdermal patches. The natural rubber patches added with mangosteen seed had high wettability and good mechanical properties. The Fourier-transform infrared (FTIR) spectra of mangosteen seed were consistent with the FTIR spectra of commercial glucosamine.     

Critical heat flux of a two-phase closed thermosyphon with fins

Journal of Mechanical Science and Technology - The critical heat fluxes (CHFs) of two-phase closed thermosyphons with and without fins were studied. The thermosyphons were fabricated using...     

Application of a simple enthalpy‐based pyrolysis model in numerical simulations of pyrolysis of charring materials

A new, simple pyrolysis model for charring materials is applied to several numerical and experimental test cases with variable externally imposed heat fluxes. The model is based on enthalpy. A piecewise linear temperature field representation is adopted, in combination with an estimate for the pyrolysis front position. Chemical kinetics are not accounted for: the pyrolysis process takes place in an infinitely thin front, at the ‘pyrolysis temperature’. The evolution in time of pyrolysis gases mass flow rates and surface temperatures is discussed. The presented model is able to reproduce numerical reference results, which were obtained with the more complex moving mesh model. It performs better than the integral model. We illustrate good agreement with numerical reference results for variable thickness and boundary conditions. This reveals that the model provides good results for the entire range of thermally thin and thermally thick materials. It also shows that possible interruption of the pyrolysis process, due to excessive heat losses, is automatically predicted with the present approach. Finally, an experimental test case is considered. Copyright © 2009 John Wiley & Sons, Ltd.     

Validation of measures of parents' preoperative anxiety and anesthesia knowledge

Parents' anxiety about their children's anesthesia may adversely affect the children's outcomes and compromise the quality of informed consent. Studies of these issues have been limited by the lack of validated measures of parental anxiety and knowledge surrounding anesthesia. In the present study, we evaluated psychometric properties of the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and the Standard Anesthesia Learning Test (SALT) among 85 parents who participated in an evaluation of the effects of a videotape about pediatric anesthesia. The results supported the internal consistency, test-retest reliability, and concurrent validity of both instruments and documented the equivalence of two forms of the SALT. Factor analysis supported the previously demonstrated factor structure of the APAIS, further confirming its construct validity. We conclude that the APAIS and SALT are reliable and valid measures of parental anxiety and knowledge of pediatric anesthesia that can be used for clinical and research purposes. Implications: This study verified the reliability and validity of two questionnaires for measuring parents' knowledge and anxiety about pediatric anesthesia. These questionnaires can be used in further research on factors affecting parental anxiety and knowledge before their children's surgery.     

Physical and functional interactions between the herpes simplex virus UL15 and UL28 DNA cleavage and packaging proteins

Herpes simplex virus (HSV) DNA is cleaved from concatemers and packaged into capsids in infected cell nuclei. This process requires seven viral proteins, including UL15 and UL28. UL15 expressed alone displays a nuclear localization, while UL28 remains cytoplasmic. Coexpression with UL15 enables UL28 to enter nuclei, suggesting an interaction between the two proteins. Additionally, UL28 copurified with UL15 from HSV-infected cells after ion-exchange and DNA affinity chromatography, and the complex sedimented as a 1:1 heterodimer upon sucrose gradient centrifugation. These findings are evidence of a physical interaction of UL15 and UL28 and a functional role for UL15 in directing UL28 to the nucleus.     

hMLH1 promoter methylation and lack of hMLH1 expression in sporadic gastric carcinomas with high-frequency microsatellite instability

The frog intermediate lobe consists of a single endocrine cell type, the melanotrope cells, which are under the tonic inhibitory control of dopamine. Separation of dispersed pars intermedia cells in a Percoll density gradient has revealed the existence of two melanotrope cell subpopulations, referred to as high-density (HD) and low-density (LD) cells. The aim of the present study was to investigate the effects of dopamine on each of these melanotrope cell subsets. Increasing doses of dopamine, ranging from 10(-9)-10(-6) M, inhibited the release of alpha-melanocyte-stimulating hormone (alpha-MSH) in LD (but not in HD) melanotrope cells. In addition, dopamine provoked a significant reduction of the rate of acetylation of alpha-MSH in LD cells but not in HD cells. Similarly, dopamine significantly decreased the accumulation of POMC messenger RNA in LD cells, whereas it did not affect POMC gene expression in the HD melanotrope subset. On the other hand, microfluorimetric studies revealed that dopamine induced a significant reduction of KCl-stimulated cytosolic free calcium concentration in both LD and HD cells. The present study provides additional evidence for functional heterogeneity of melanotrope cells in the frog pars intermedia. Because dopamine plays a pivotal role in the regulation of alpha-MSH secretion, these data suggest the involvement of cell heterogeneity in the physiological process of background color adaptation in amphibians.     

Inhibition of feline collateral vessel development following experimental thrombolic occlusion

We compared development of feline hindlimb collateral circulation after acute occlusion of the terminal aorta by ligation, thrombus formation, and formation of a "closed" aortic loop containing thromboplastin. Collateral circulation development was assessed by aortograms, scintillation scans, neurological signs following occlusion, measurement of hindlimb muscle blood flow, and forelimb and hindlimb temperature. In cats in which aortic occlusion was the result of ligation or thromboplastin in the aortic loop, paralysis was not evident. Aortograms and scintillation scans indicated hindlimb blood flow. Both muscle temperature and blood flow data indicated that the return of blood flow was rapid. The 5th lumbar artery appears to be the origin of the collateral vessels. The mid-zone component is a dorsal and ventral vertebral route and an epaxial muscle route. The reentry components are the 6th or 7th lumbar arteries. The collateral vessels arise from preexisting collateral vessels. Of those cats in which aortic occlusion was the result of a thrombus, all exhibited paralysis. Aortograms, scintillation scans, muscle temperature, and hindlimb blood flow data indicated reduced hindlimb blood flow. The results suggest that the thrombus has an inhibitory effect on the development of collateral circulation.     

TCR-independent pathways mediate the effects of antigen dose and altered peptide ligands on Th cell polarization

We examined the role of the peptide/MHC ligand in CD4+ T cell differentiation into Th1 or Th2 cells using a TCR alphabeta transgenic mouse specific for hemoglobin (Hb)(64-76)/I-Ek. We identified two altered peptide ligands of Hb(64-76) that retain strong agonist activity but, at a given dose, induce cytokine patterns distinct from the Hb(64-76) peptide. The ability of these peptides to produce distinct cytokine patterns at identical doses is not due to an intrinsic qualitative property. Each peptide can induce Th2 cytokines at low concentrations and Th1 cytokines at high concentrations and has a unique range of concentrations at which these distinct effects occur. The pattern of cytokines produced from limiting dilution of naive T cells demonstrated that the potential to develop an individual Th1 or Th2 cell is stochastic, independent of Ag dose. We propose that the basis for the observed effects on the Th1/Th2 balance shown by the altered peptide ligands and the amount of Ag dose involves the modification of soluble factors in bulk cultures that are the driving force that polarize the population to either a Th1 or Th2 phenotype.