1,720,968 research outputs found
Ocular delivery of antisense oligonucleotides using colloidal Carriers: improving the wound repair after corneal surgery
No full textBackground and Aim: Clinical outcomes of refractive surgeries are variable due to
individual wound healing responses, but might be improved by effective delivery of
anti-inflammatory agents. Knockdown of connexin proteins, using an antisense
oligonucleotide (AsON) approach, has been shown to significantly reduce the
inflammatory response and increase the rate of wound closure after corneal laser
surgery. The challenge remains to find delivery systems that are easy to apply, but can
still effectively deliver the AsONs to the target site. This thesis aimed to evaluate the
efficacy of several in-situ gelling formulations to deliver Cx43 AsONs to the wounded
tissues of a rat corneal scrape wound model.
Methods: Formulations were characterised in terms of their rheological behaviour,
microstructure and spreading ability. They were then evaluated for their irritation
potential, precorneal retention and ability to control the release of the model hydrophilic
drug pilocarpine hydrochloride both in vitro and in vivo. The stability of the AsONs in
these formulations was assessed using Fluorescence Resonance Energy Transfer.
Finally, formulations containing the stable AsONs were applied to a rat corneal scrape
wound model and penetration depth, wound size after 12 hours and cellular dynamics
underlying the wound healing response were analysed.
Results and Discussion: Systems based on gellan gum, xanthan gum, carrageenan and
alginate underwent sol-to-gel phase transition upon addition of the cations present in
tear fluid. All tested systems exhibited favourable contact angles and were found to be
non-irritant. Systems based on gellan gum, xanthan gum and carrageenan showed the
longest ocular retention and exhibited the slowest release characteristics both in vitro
and in vivo. AsONs were found to be stable in all formulations apart from the chitosan
system, where precipitation occurred. This formulation also exhibited the slowest
wound healing rate due to induction of a pro-inflammatory response. Conversely,
delivery of the AsONs by gellan gum and carrageenan formulations resulted in
significant reduction in wound size, inflammatory response and Cx43 levels.
Conclusion: In-situ gelling systems based on gellan gum and carrageenan are able to
successfully deliver Cx43 AsONs to the wounded tissues and therefore improve the
healing response after corneal surgery
Oral dosage forms and drug delivery systems: tablets, oral films, liquid dosage forms, oral bioavailability enhancement
No full textCharacterisation of delayed release granules for diphacinone: formulation for the control of brushtail possum in New Zealand
No full textBackground and Aim: The common brushtail possum (Trichosurus velpecula) causes more damage to the environment than any other vertebrate species in New Zealand. The use of poison remains the main method for possum population control. Diphacinone is an anticoagulant that produces toxic effects by inhibiting the production of vitamin K–dependent coagulation factors which lead to profuse haemorrhage and eventually, death. The objective of this thesis was to investigate the potential of diphacinone as a toxin for the control of possum population in New Zealand.
Methods: The preformulation of diphacinone included the development and validation of an analytical method, spectral identification, investigation of melting behaviour, solubility, and the determination of ionisation constant. The permeability of diphacinone across the ileal tissue of possum was assessed using a modified Ussing chamber model. Diphacinone granules were developed to prolong drug release and retention by in vitro dissolution and tensile testing. A factorial study was employed to optimise the granulation process by identifying significant process variables that influenced the yield percentage, size distribution and water uptake of granules
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Ocular, otic, nasal, rectal and vaginal formulation innovations and regulatory considerations
Full text linkVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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