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Physicomechanical properties of bacterial P(HB-HV) polyesters and their uses in drug deliveryAkhtar, Saghir January 1990 (has links)
No description available.
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Nanosponges for advanced drug deliveryYapa, Asanka Sajini January 1900 (has links)
Doctor of Philosophy / Department of Chemistry / Stefan Bossmann / A novel type of supramolecular aggregate, named "nanosponge" was synthesized through the interaction of novel supramolecular building blocks with trigonal geometry. The cholesterol-(K/D)[subscript n]DEVDGC)₃-trimaleimide unit consists of a trigonal maleimide linker to which homopeptides (either K or D) of variable lengths (n = 5, 10, 15, 20) and a consensus sequence for executioner caspases (DEVDGC) are added via Michael addition. Upon mixing in aqueous buffer, cholesterol-(K)[subscript n]DEVDGC)₃-trimaleimides, as well as a 1:1 mixture of cholesterol-(K/D)[subscript n]DEVDGC)₃-trimaleimides form stable nanosponges, whereas cholesterol-(D)[subscript n]DEVDGC)₃-trimaleimide is unable to form supramolecular aggregates by itself. The structure of the novel nanosponges was revealed through explicit solvent and then coarse-grained molecular dynamics (MD) simulations. The nanosponges are between 80nm and several micrometers in diameters and virtually non-toxic to monocyte/macrophage-like cells.
Furthermore, the structure of novel binary nanosponges consisting of cholesterol-(K/D)[subscript n]DEVDGC)₃-trimaleimide units possessing a trigonal maleimide linker, to which either lysine (K)₂₀ or aspartic acid (D)₂₀ are tethered, has been elucidated by means of TEM. A high degree of agreement between these findings and structure predictions through explicit solvent and then coarse-grained molecular dynamics (MD) simulations has been found. Based on the nanosponges’ structure and dynamics, caspase-6 mediated release of the model drug 5(6)-carboxyfluorescein has been demonstrated. Moreover, the binary (DK20) nanosponges have been found virtually non-toxic in cultures of neural progenitor cells. Additionally, DK20 nanosponges were taken up efficiently by leucocytes (WBC) in peripheral blood within 3h of exposure. The percentage of live cells among the WBC was not significantly decreased by the DK20 nanosponges. Therefore, this novel material holds great promise for improved cell-mediated therapy.
Two different nanosponges loaded with the anticancer agent perillyl alcohol (POH) were developed to test the suitability of nanosponges for cell-based cancer therapy. Drug-loaded nanoshuttles featuring trigonal supramolecular building blocks, type (D-POH)₁₀K₂₀ and (D-POH)₁₀R₂₀ were synthesized, purified, and characterized by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). They were then tested in cell cultures of murine glioma cells (GL26) and murine neural progenitor cells (NPC). The two nanosponges exhibited significantly different biophysical properties (size distribution and zeta potentials). Consequently, different efficacies in killing GL26 and NPC were observed in both, serum free and serum containing culture media. The results from these experiments confirmed that type (D-POH)₁₀K₂₀ nanosponge is an excellent candidate for the cytotherapy of glioblastoma.
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Targeted delivery in vitro from magnetic vesicle gelsDe Cogan, Felicity Jane January 2013 (has links)
Membrane sacs, known as vesicles and liposomes have been widely used as stores for bioactive materials both in vitro and in vivo. The vesicles are biocompatible and in vitro experiments often use them in conjunction with magnetic nanoparticles. The magnetic nanoparticles allow the liposomes to be magnetically located and act as a trigger for release of the encapsulated materials. However, these magnetic vesicles or 'magnetoliposomes' as they are also known have not mananged to cross the barrier into clinical use. The work in this thesis aims to develop a novel system of magnetoliposomes for use in a biological environment. Magnetoliposomes are created from phospholipid suspensions extruded to give a spherical bilayer membrane. This membrane is doped with biotinylated lipids. These lipids are key to allowing the system to work in vitro. The magnetic nanoparticles are formed from iron and are coated with a novel synthetic linker to allow them to interact with the liposomes. When the liposomes and the nanoparticles are mixed in the presence of the protein avidin, large heirarchacal structures are formed which are stable under physiological conditions. The magnetoliposomes are held in an alginate hydrogel scaffold which acts as a support for the liposomes and as an adherent cell scaffold for tissue culture. This work demonstrates that this system can be used to encapsulate and release a range of bioactive molecules such as nickel chloride as a mimic for cytotoxic cancer drugs, ascorbic acid-2-phosphate for the upregulation of collagen production in chondrocytes and SB 431542 for the differentiation of mouse embryonic stem cells. The results shown in this work demonstrate that it is possible to use this novel linking system to create a new form of magnetoliposomes which are stable, biocompatible and easy to form and use. This work also demonstrates a strong model for possible drug delivery in vivo.
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Configuration of a multi-layered multi-disk tablet for specialized drug deliveryKhan, Zaheeda 06 March 2012 (has links)
M. Pharm., Dept. of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 2011 / Chronotherapy is a form of therapy where treatment is administered according to a schedule that corresponds to an individual’s biological clock. Research demonstrates that the body’s natural processes follow a 24-hour pattern, or circadian rhythm. In addition, symptoms of disease fluctuate according to this 24-hour pattern. These diseases, termed chronotherapeutic disorders may include amongst other disorders, hypertension, cardiovascular disease and asthma. Common therapy for these disorders involves the use of controlled zero-order release formulations. Here, the same quantity of drug is released over a period of time. Although beneficial, these formulations are not ideal in the treatment of chronotherapeutic disorders. Treatment of these disorders aims to release drug at specific periods, only when it is required, such that therapy coincides with the body’s natural rhythm. Ideally, drug should be released in pulses with two or more pulses released from the dosage form. In this manner, the patient is exposed to drug only when required, reducing the number of dosages, reducing side-effects and ultimately increasing patient compliance. Therefore, the aim of this research was to develop a Multi-Layered Multi-Disk Tablet (MLMDT) that incorporates two drug-loaded disks enveloped by three polymeric layers. The proposed system, to be used in the treatment of chronotherapeutic disorders, is designed to provide a lag phase and then two pulses of drug release separated by a ‖switch-off‖ phase. During the ―switch-off‖ phase no drug is released from the system.
Initially, preliminary screening studies were performed on various polymeric materials to assess their effectiveness to generate the desired drug release profile. Of the numerous polymer combination and ratios, only a few were relevant and were subsequently tested further. From the preliminary studies it was ascertained that the composition of disk 2 was critical in generating the ―switch-off‖ phase separating the two pulses. Artificial Neural Networks (ANN); a computational technique that simulates the thinking process of the human brain was employed for optimization. Results from this technique outlined the polymer combination suitable for the optimized MLMDT. The optimized formulations were subjected to friability, hardness and uniformity of mass analysis as well as swelling, erosion and magnetic resonance imaging techniques to observe and confirm the performance of the MLMDT during dissolution. In addition, textural analysis, computational modeling and temperature modulated differential scanning calorimetry techniques were used to elucidate any incompatibilities or complexes formed. In vitro drug release analysis revealed that the MLMDT generated a lag phase followed by two pulses of drug release over the 24 hour period. The two pulses were separated by a ―switch-off‖ phase.
To confirm data obtained during preclinical in vitro testing, animal studies were undertaken using the Large White Pig model. Pigs were dosed with conventional products and the optimized MLMDT. Blood samples collected over a 24 hour period were analyzed using Ultra Performance Liquid Chromatography to determine the drug concentration in blood. Drug concentration analysis from conventional products revealed increasing plasma concentrations up to 2 hours followed by a steady decline in concentration while the developed MLMDT displayed two pulse drug release separated by a ―switch-off‖ phase.
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Oral electrospun multi-component membranous drug delivery systemsShaikh, Rubina Perveen 18 March 2013 (has links)
Oral drug delivery is perceived by many as the ideal method of drug delivery due to its versatility, ease and
convenience. However, the bioavailability of drugs delivered via the oral route remains questionable.
Typically, conventional marketed drug delivery systems release drugs in variable and erratic fashions, causing
sub-therapeutic or even toxic doses. As a result, patient compliance is threatened, ultimately affecting the
success of the therapeutic intervention. Furthermore, the harsh gastric environment further compromises oral
bioavailability due to the presence of a highly acidic environment and proteolytic enzymes.
A multi-component, membranous drug delivery system (MMDDS) was thus designed, formulated and
evaluated for the site-specific delivery of two (or more) drugs in a prolonged release manner, ultimately easing
complicated treatment regimens, and improving patient compliance. The MMDDS essentially comprises of a
gastric-targeted and an intestinal-targeted component, each containing a protective coat, a drug-loaded layer
incorporating the respective drugs, and a pH-responsive mucoadhesive layer for site-specific mucoadhesion.
The MMDDS employs a combination of controlled and targeted drug release mechanisms, in addition to
gastro-retentive or intestinal retentive mechanisms. Furthermore, the system physically protects the drug
delivery system from acidic or proteolytic degradation within the human gastro-intestinal tract. The present
study employed the use of pH-dependant mucoadhesion for site-specific, segregated and gastroretentive drug
delivery while crosslinking was employed for rate-modulated drug delivery. Rifampicin and isoniazid were
selected as the model drugs in this study as they are known for interacting when administered simultaneously
(detrimentally affecting the bioavailability of rifampicin). Notwithstanding this interaction, rifampicin and
isoniazid must be taken concurrently for successful TB therapy. Therefore these drugs would benefit from the
site-specific drug delivery offered by the MMDDS.
The primary aim of the pH-responsive mucoadhesive layer was to ensure prolonged adhesion of the MMDDS
at a specific site within the human gastro-intestinal tract. The pH-responsive mucoadhesive layer was the
fundamental aspect that promoted site-specific and segregated drug delivery. Preliminary in vitro
investigations led to the identification of a combination of polymers best suited to develop the respective pHresponsive
mucoadhesive layers. A central composite design was employed to determine the optimal ratios of
the polymers selected which would impart the largest degree of mucoadhesion within the respective pH
ranges. Each mucoadhesive layer was thereafter optimized and subject to various in vitro investigations to
determine the effects of the GIT on the properties of the mucoadhesive layer, as well as determine the
behaviour of the mucoadhesive layer when subject to simulated gastrointestinal conditions.
Electrospinning, a versatile technique employed in the fabrication of fibres in the nanometre size range, was
employed to develop the drug loaded layer. Poly(vinyl alcohol) (PVA) nanofibres were thereafter crosslinked
employing glutaraldehyde vapours to ensure controlled release of the incorporated drugs. The drug-loaded
layer demonstrated good versatility in incorporating vastly different drugs, with only minor adjustments to the
fabrication procedure. Furthermore, PVA demonstrated good loading of rifampicin and isoniazid, and near
zero-order drug release was achieved after the crosslinking procedure. Prolongation of drug release
fundamentally decreases the numbers of doses required to be taken daily, and as such, patient compliance is
improved.
Furthermore, in vitro analysis revealed that the developed MMDDS behaved superiorly in terms of controlling
drug delivery in a site-specific and prolonged fashion in comparison to a marketed gold standard formulation,
Rifinah®. These findings were further substantiated by in vivo analysis, which was conducted in a swine
model. Results indicated that minimal release of isoniazid was observed in the stomach, based on the plasma
concentrations of the drug. Release of isoniazid was initiated only when the intestinal-targeted component
entered the intestine of the pig, corresponding to higher plasma concentrations of isoniazid. In this manner,
the delivery of isoniazid and rifampicin was segregated, thus improving the oral bioavailability of rifampicin.
To summarize, the MMDDS was able to overcome the many challenges associated with oral drug delivery, by
easing complicated treatment regimens, and improving the bioavailability of drugs delivered orally. The
benefits associated with oral drug delivery have clearly been exploited by the present study, producing a
versatile drug delivery “tool” which can successfully be adapted to incorporate any number of drugs (including
an entire treatment regimen in one dosage form!) for targeted delivery within the human gastro-intestinal tract
in a prolonged manner.
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Processing and characterization of polymer microparticles for controlled drug delivery systemsChakrapani, Aravind 30 November 2006 (has links)
No description available.
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In Vitro Characterization Of Simvastatin Loaded Microspheres In The PolyRing DeviceVishwanathan, Anusha 12 May 2008 (has links)
No description available.
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Photoresponsive Drug Delivery From Anthracrene-Modified HydrogelsWells, Laura 11 1900 (has links)
<p> Photoresponsive polymers can act as controllable drug delivery systems that may
revolutionize ophthalmic drug delivery for disease treatment in the posterior segment of
the eye. Localized, controlled drug delivery devices have significant therapeutic
advantages for treating diseases of back of the eye by increasing patient compliance and
maintaining therapeutic levels of drug in the tissue. Sustained-release delivery systems
that respond to light/laser stimuli are under development to control the rate of delivery
resulting in a tuneable treatment profile ideal for retinal diseases. The use of light as a
crosslinking mechanism has the potential to create unique materials with controllable
swelling, degradation and diffusion properties. </p> <p> This thesis investigates the synthesis and development of universal, graftable
PEG-anthracene molecules and their applications in photosensitive alginate and
hyaluronate (HA) "photogels". Anthracene undergoes reversible dimerization with
wavelengths above 300 nm and de-dimerization/dissociation below 300 nm; due to its
well-understood chemistry and symmetry, it was used as a starting point and proof-ofconcept
for the synthesis of reversible dimerizing crosslinkers that may be generically
grafted to different polymers to cause crosslinking/decrosslinking. After synthesis, watersoluble
PEG-anthracene macromolecules were grafting via carbodiimide chemistry to the
carboxyl groups along the polymer backbone of alginate and HA at various densities to
create viscous liquids or gels with good handling properties. </p> <p> Light irradiation can be used to control the swelling and effective crosslinking
density of the photogels which in tum can control drug delivery from photocrosslinked hydro gels as illustrated through the decrease or increase in the delivery of a variety of low
molecular weight (<1000 Da) and high molecular weight (>10,000 Da) model drug
compounds from both alginate and HA photogels with various light treatments. Novel
loading mechanisms were developed through the loading of compounds into
uncrosslinked gels followed by crosslinking 365 nm exposures to "lock" in the model
drug compounds. Diffusion coefficients effectively compared the different systems
showing increase exposures of 365 nm resulted in greater decrease in release of
compounds demonstrating the ability to fine-tune release rates. Different formulations
and control gels demonstrate a variety of different release profiles. The photogels were
valuable long-term controlled release systems (>80 days) that also demonstrate high
cytocompatibility when grown with ophthalmic cell lines. </p> <p> Novel photoresponsive biomaterials for smart delivery of therapeutics which use
light-controlled crosslinking and decrosslinking mechanisms have been developed. The
PEG-anthracene graftable photocrosslinkers show the ability to introduce photocontrolled
crosslinking into hydrogel systems. While anthracene as the photodimerizer
and alginate and HA as the bulk materials are used as a proof-of-concept in this work, this
grafting system can be further manipulated to include new photosensitive dimerizers and
other applicable polymers. The ability to use light stimuli to control release rates in a
continual fashion, rather than having delivery that is strictly on or off, is a valuable
finding that may lead to the development of drug delivery systems that can be catered
towards individuals and the progression of their disease. </p> / Thesis / Doctor of Philosophy (PhD)
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A lipidic amino acid based system for peptide delivery and enhancing peptide immunogenicityFlinn, Nicholas Sean January 1996 (has links)
No description available.
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The effect of Carbopol 934 rheological polymers on the dissolution rate of sulphamide crystalsMuungo, Lungwani Tyson Makoye January 1995 (has links)
No description available.
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