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Micropores Fabricated Using Undercut Etching Techniques for Ultra Small Droplets Formation and Its Pharmaceutical ApplicationsLan, Chun-Hung 09 September 2010 (has links)
This research successfully created an ultra-small orifice utilizing undercut fabrication process in a droplet-based microfluidics chip. The proposed novel T-junction structure with ultra-small orifice has a lot of advantages, including long-term stability for uniform droplets formation, reproducible ultra-small size droplet and tunable droplet size. The hydraulic diameter of the orifice is under 2 £gm, and the size of micro droplet produced from the orifice can be tuned to less than 10 £gm in diameter. Chitosan droplet can be produced by the proposed chip, which is usually adopted for medical applications. Surface modification technique was applied to modify the surface of microchannel to be hydrophobic for eaily producing hydro-droplets. Experimental results show that the ultra-small orifice microfluidics chip can steadily produce water-in-oil droplets only by controlling the flow ratio between dispersed phase and continuous phase flow rates. The size of the water-in-oil droplets can be tunable from 22 £gm to 6.5 £gm in diameter by adjusting the flow rate ratio of the continuous and disperse phase flows from 1 to 3.5 and the hydraulic diameter of the orifice is 1.1 £gm. And the size of the chitosan-in-oil droplets also can be tunable from 59 £gm to 27 £gm by adjusting the flow rate ratio of the continuous and disperse phase flows from 4 to 8. The proposed microchip has advantages including ease of control, low cost, and high throughput. The proposed technique can be widely applied on emulsion and micro droplet generation.
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Auto Template Assembly of CaCO3-Chitosan Hybrid Nanoboxes and Nanoframes in Ionic Liquid MediumChen, Hsingming Anna 2011 May 1900 (has links)
Recently, there has been increased effort in researching methods for producing hollow nanostructures because of their potential impact in the fields of catalysis, separation processes, drug delivery, and energy storage and conversion devices. The purpose of this thesis is to describe a method for forming hollow inorganic-organic hybrid nanoboxes and nanoframes. This approach relies upon ionic liquid (1-butyl-3-methyl-imidazolium chloride) mediated auto-templating assembly of CaCO3 and chitosan to form nanoframes (two open faces) and nanoboxes (one open face).
The average dimension of the nanostructures formed was 339 ± 95 x 299 ± 89 nm. Detailed structure of nanoboxes and nanoframes were obtained by 3-D electron tomography and X-ray diffraction. Chemical bonding was determined by FTIR, and the ratio of organics to inorganics in the nanostructures was determined by thermal gravimetric analysis. The chitosan to CaCO3 weigh ratio, mixing strength, temperature, and dialysis time were varied to further elucidate the method of formation. It was found that increasing the mixing power caused the equilibrium nanostructure dimension to decrease. On the other hand, varying the experimental temperature in the range of 80 to 160˚C did not affect the nanostructure dimension. The dialysis study showed that during dialysis the nanostructure core was increasingly removed. Nanoframes were observed after 72 hours of dialysis. With further dialysis, there was continued erosion of nanoframes. Results indicate that the concentration gradient and the solubility difference between the mixture components were responsible for this transformation.
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Role of scaffold topography and stimulation via ultrasound on the biosynthetic activity of chondrocytes seeded in 3D matricesNoriega, Sandra January 2009 (has links)
Thesis (Ph.D.)--University of Nebraska-Lincoln, 2009. / Title from title screen (site viewed January 5, 2010). PDF text: xiv, 328 p. : ill. (some col.) ; 7.48 Mb. UMI publication number: AAT 3373081. Includes bibliographical references. Also available in microfilm and microfiche formats.
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BMP2 gene delivery mediated by chitosan-ss-PEI non-viral vector and investigation of BMP2 signaling regulationZhao, Xiaoli, 赵晓丽 January 2011 (has links)
Osteoporotic fractures are still the major health concerns in many developed
societies especially when the incidence of that tremendously increased with the aging
population. However, the outcomes of osteoporotic fracture treatment have not been
entirely satisfactory due to the poor quality of bone substance. Inspiringly, bone
morphogenetic protein 2 (BMP2) with the ability to accelerate bone formation
showed advantages over the conventional treatment. The only problem needed to
overcome is its short half-life which resulted in the requirement of readministration
and extremely high cost. As a solution to that, gene therapy provides a promising way
to sustainably release this protein at the regeneration site. Since viral vectors have
been hampered by genetic toxicity and immunogenicity, nanoscaled non-viral vectors
offer an attractive means for gene delivery.
Chitosan as non-viral vector has been widely investigated for its excellent
biocompatibility. Most efforts have been given to improve its low transfection
efficiency. In this study, chitosan was first modified with octaarginine, one of cell
membrane penetrating peptides, and showed enhanced transfection activity, but which
was not significant as expected. Following that, low molecular weight
polyethyleminine (PEI) was introduced to modify chitosan through bioreducible
disulfide linkage, denoted as Chitosan-ss-PEI. PEI is an efficient non-viral vector but
hampered by molecular-weight dependent toxicity. The developed Chitosan-ss-PEI
showed good biocompatibility in MTT assay in three different cell lines, during which
cells were maintained 80% of viability when the concentration of this vector was up
to 100 μg/mL. The optimal transfection efficiency of Chitosan-ss-PEI was higher than
that of PEI 25k and comparable to Lipofectamine in delivering luciferase reporter
gene. GFP expression mediated by Chitosan-ss-PEI also showed similar results.
Chitosan-ss-PEI was then applied to deliver BMP2 gene to skeletal system cells
and exhibited the osteogenic ability. For C2C12 myoblast cells, this system inhibited
their myoblast differentiation and induced the osteogenic differentiation. It also
showed stronger effect in promoting the differentiation of immature osteblast-like
MG63 cells and in inducing C3H10T1/2 mesenchymal stem cells osteogenic
differentiation in term of ALP activity and mineralization ability compared with other
commercial available non-viral vectors. Primary MSCs such as bone marrow stromal
cells (BMSC) and human umbilical cord blood mesenchymal stem cells
(hUCB-MSC), are usually more difficult to transfect, but they showed stronger
osteogenic differentiation ability induced by this system comparing with the cell lines.
BMP2 usually requires extremely high concentration to realize its function.
Through the investigation of BMP2 signaling regulation in this study, it was found
that parathyroid hormone (PTH) could increase the access of BMP2 ligands to their
receptors by negatively influencing BMPs antagonist network, resulted in enhanced
BMP2 activity in bone remodeling and in promoting the commitment of MSC to
osteoblast lineage both in vitro and in vivo. This course involved the endocytosis of
PTHR with a complex of LRP6, which organized antagonist network on the cell
surface to shield the BMPs receptors. Novel approaches are expected to be developed
based on this mechanism with the purpose of intensifying the therapeutic effect of
BMPs. / published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy
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Optimisation of conditions for the resolution of 1,2-epoxyoctane in a bioreactor / I. le RouxLe Roux, Ilani January 2003 (has links)
Due to recent legislation requiring the determining of the pharmacokinetic effect of both
enantiomers separately, of any new racemic drug before commercialisation, much research is
done to improve and optimise methods for obtaining chirally pure compounds important for the
pharmaceutical industry, for example epoxide precursors.
To date most experiments regarding the biocatalytic chiral separation of 1,2-epoxyoctane has
been done in batch processes. The aim of this study was to optimise the enantioselective
hydrolysis of 1,2-epoxyoctane by Rhodosporidiurn tondoides in both a batch and continuous
process. The batch process was optimised in terms of stir speed, biomass (cell) concentration
and reaction time, while the flow-through reactor (continuous process) was optimised with
regards to the flow rate as a function of the pressure and the amount of chitosan and biomass in
the reactor.
Initial inconsistencies of epoxide concentrations in preliminary studies were found to be due to
adsorption by reaction and sampling vessels, and the lower than expected solubility of 1,2-
epoxyoctane (3.85 mM instead of 6 mM as reported by previous investigators).
The results from the batch process suggest that as the reaction time increases, the % ee-epox
increases initially, but decreases after 40 minutes. Optimum yield in terms of % ee-epox were
obtained at medium stir speed (400 rpm) and biomass (cell) concentration (13 %). Below these
values the % ee-epox increases with an increase in stir speed and/or biomass concentration.
Above these values however, the increased stir speed and/or biomass concentration causes
abrasion between cells, which negatively affects the % ee-epox. The % ee-diol reached a steady
state after 10 minutes, and the effect of the different operating conditions on % ee-diol was
negligible.
In the flow-through reactor chitosan was used as a spacer material (antifouling agent) to help
decrease the fouling due to biomass deposition. The use of chitosan as a spacer ensured
higher and stabilised flow rates for extended periods of time. In initial studies 0.5 g chitosan
increased the flow rate by 34 % with a resistance removal of 25 %. For 1 g chitosan these
values were 130 % flow increase and 57 % resistance removal. The flow rate was optimised in
relation to the chitosan amount, biomass (cell) amount and pressure. The maximum flow rate
was obtained at a pressure of 40 kPa, using the minimum amount of cells (0.4 g) and a
maximum amount of chitosan (1.6 g) / Thesis (M.Sc.)--North-West University, Potchefstroom Campus, 2004.
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Dažų adsorbcijos krabų chitinu ir chitozanu kinetika bei pusiausvyra / Kinetics and equilibrium adsorption of dye on crabs chitin and chitosanČivilienė, Loreta 13 June 2005 (has links)
Chitin, chitosan recovered from fly crabs shells have been investigated by the elemental analysis, potentiometric titraton and FT–IR spectrometry methods. The molecular weght of chitosan was determined by measuring their viscosity. The adsorption kinetics of reactive dye and equilibrium conditions has been investigated. The adsorption of reactive dye on chitin and chitosan proceeds according to pseudo – second – order kinetic equation. Adsorption investigations under equilibrium conditions showed that. Theses results were fitted by both Langmuir and Freudlich models.
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Bioactive Chitosan Nanoparticles and Photodynamic Therapy Inhibit Collagen Degradation in vitroPersadmehr, Anousheh 09 December 2013 (has links)
This study evaluated the ability of photodynamic therapy (PDT), chitosan nanoparticles
(CSnp), or their combination, to inhibit bacterial collagenase-mediated degradation of
collagen. Rat type 1 fibrillar collagen matrices were untreated or treated with 2.5%
glutaraldehyde (GD), 2.5% GD followed by 1% CSnp, 1% CSnp, PDT, or 1% CSnp
followed by PDT. Samples, except untreated controls, were exposed to Clostridium
histolyticum collagenase. The soluble digestion products were
assessed by hydroxyproline assay and the remaining adherent collagen was quantified by
picrosirius red (PSR) staining. Collagen treated with CSnp, PDT, or a combination of
CSnp and PDT, exhibited less degradation than controls. The abundance of posttreatment
residual collagen correlated with the extent of degradation. Fourier transform
infrared (FTIR) spectroscopy analysis showed that PDT treatment enhanced collagen
cross-linking. Immunoblotting of sedimented CSnp indicated that CSnp and collagenase
bound with low affinity. However, CSnp-bound collagenase showed a significant
reduction in collagenolytic activity compared with controls.
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Bioactive Chitosan Nanoparticles and Photodynamic Therapy Inhibit Collagen Degradation in vitroPersadmehr, Anousheh 09 December 2013 (has links)
This study evaluated the ability of photodynamic therapy (PDT), chitosan nanoparticles
(CSnp), or their combination, to inhibit bacterial collagenase-mediated degradation of
collagen. Rat type 1 fibrillar collagen matrices were untreated or treated with 2.5%
glutaraldehyde (GD), 2.5% GD followed by 1% CSnp, 1% CSnp, PDT, or 1% CSnp
followed by PDT. Samples, except untreated controls, were exposed to Clostridium
histolyticum collagenase. The soluble digestion products were
assessed by hydroxyproline assay and the remaining adherent collagen was quantified by
picrosirius red (PSR) staining. Collagen treated with CSnp, PDT, or a combination of
CSnp and PDT, exhibited less degradation than controls. The abundance of posttreatment
residual collagen correlated with the extent of degradation. Fourier transform
infrared (FTIR) spectroscopy analysis showed that PDT treatment enhanced collagen
cross-linking. Immunoblotting of sedimented CSnp indicated that CSnp and collagenase
bound with low affinity. However, CSnp-bound collagenase showed a significant
reduction in collagenolytic activity compared with controls.
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Optimisation of conditions for the resolution of 1,2-epoxyoctane in a bioreactor / I. le RouxLe Roux, Ilani January 2003 (has links)
Due to recent legislation requiring the determining of the pharmacokinetic effect of both
enantiomers separately, of any new racemic drug before commercialisation, much research is
done to improve and optimise methods for obtaining chirally pure compounds important for the
pharmaceutical industry, for example epoxide precursors.
To date most experiments regarding the biocatalytic chiral separation of 1,2-epoxyoctane has
been done in batch processes. The aim of this study was to optimise the enantioselective
hydrolysis of 1,2-epoxyoctane by Rhodosporidiurn tondoides in both a batch and continuous
process. The batch process was optimised in terms of stir speed, biomass (cell) concentration
and reaction time, while the flow-through reactor (continuous process) was optimised with
regards to the flow rate as a function of the pressure and the amount of chitosan and biomass in
the reactor.
Initial inconsistencies of epoxide concentrations in preliminary studies were found to be due to
adsorption by reaction and sampling vessels, and the lower than expected solubility of 1,2-
epoxyoctane (3.85 mM instead of 6 mM as reported by previous investigators).
The results from the batch process suggest that as the reaction time increases, the % ee-epox
increases initially, but decreases after 40 minutes. Optimum yield in terms of % ee-epox were
obtained at medium stir speed (400 rpm) and biomass (cell) concentration (13 %). Below these
values the % ee-epox increases with an increase in stir speed and/or biomass concentration.
Above these values however, the increased stir speed and/or biomass concentration causes
abrasion between cells, which negatively affects the % ee-epox. The % ee-diol reached a steady
state after 10 minutes, and the effect of the different operating conditions on % ee-diol was
negligible.
In the flow-through reactor chitosan was used as a spacer material (antifouling agent) to help
decrease the fouling due to biomass deposition. The use of chitosan as a spacer ensured
higher and stabilised flow rates for extended periods of time. In initial studies 0.5 g chitosan
increased the flow rate by 34 % with a resistance removal of 25 %. For 1 g chitosan these
values were 130 % flow increase and 57 % resistance removal. The flow rate was optimised in
relation to the chitosan amount, biomass (cell) amount and pressure. The maximum flow rate
was obtained at a pressure of 40 kPa, using the minimum amount of cells (0.4 g) and a
maximum amount of chitosan (1.6 g) / Thesis (M.Sc.)--North-West University, Potchefstroom Campus, 2004.
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Formulation of a chitosan multi-unit dosage form for drug delivery to the colon / Gerhardus Martinus BuysBuys, Gerhardus Martinus January 2006 (has links)
In some diseases it is preferable that the drugs used in their treatment are released in
the colon. The colon is also suitable for systemic delivery of a variety of drugs. A
variety of systems have been developed for the purpose of achieving colonic
targeting. These approaches are either drug-specific (prodrugs) or formulation
specific (coated or matrix preparations) and depends on the pH, transit time and
pressure or bacteria in the colon. Different polymers, like chitosan, have been
evaluated for their susceptibility to degradation by these bacterial enzymes. Chitosan
is considered a good candidate for bacterial degradation and is widely available at
low cost and has favourable biological properties.
To investigate the influence of formulation factors on the properties of chitosan
minitablets, it was necessary to ensure that the chitosan had satisfactory powder flow
characteristics to ensure uniform compression in the tablet press and to prevent
unacceptable variation in the tablet properties such as weight, thickness,
disintegration and strength. Moisture content of the powder, particle size and the
inclusion of glidants had an effect on the flowability and it could be improved from a
composite flow index value of 32.7 to a value of 58.8.
The compressibility of chitosan is very poor and different factors that might influence
it, was investigated. Compression forces of between 15 and 20 bar resulted in tablets
with acceptable physical characteristics. An increase in moisture content, using the
powder fraction > 212 ym as well as a decrease in powder weight resulted in tablets
with a higher tensile strength.
Lower compression forces resulted in tablets that are extremely porous. This
suggests that the chitosan can only be compressed at high compression forces
which are difficult to obtain using a standard tablet press. The standard tablet press
was therefore modified to fill more powder in the die and generate higher
compression forces. Minitablets were compressed and the dissolution of isoniazide from these tablets was
investigated. Varying the punch depth or the compaction of the powder did not result
in the desired slower release of the drug as a result. The porosity of the tablets
compressed at all the punch depth settings and compaction percentages was
probably too high to have an effect on the wettablity of the tablets and as a result on
the dissolution of the isoniazide from the tablets. The inclusion of excipients such as
citric acid (an organic acid which would lower the pH in the tablet, allowing the
chitosan to form a gel) and pectin (which would form an insoluble complex with the
chitosan) into the formulation delayed the dissolution of the isoniazide from the
minitablets.
Coating of the minitablets with an enteric coating (Eudragit S ®) initially delayed the
dissolution of the isoniazide and would protect the tablets from the harsh
environment of the stomach so that the tablets will reach the colon and release the
drug. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007
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