Veterinary Science Collected Works - Theses
Permanent URI for this collection
Search Results
1 - 2 of 2
-
ItemInvestigation on Wound Healing Properties of Novel Selenium Compounds and Honey Bioactives( 2022-12)When the functional or structural integrity of the skin is compromised by various physical, chemical or microbial injuries, an automatic and organised multi-step process of wound healing occurs to repair the damaged tissues. However, various factors, such as age or underlying conditions, including cardiovascular disease, ischaemia, diabetes and infection, may contribute to impaired healing and result in non-healing chronic wounds. The chronicity of wounds has become a major global challenge impacting on a patient’s quality of life by increasing the morbidity rate and leading to amputations, imposing a high economic burden on health systems. Knowledge about the physiology of the wound healing process and its underlying mechanisms has been advanced over the past few decades using animal models. Various treatments have been proposed, which have focused directly on their effects on the immunohistopathological appearance of wounds or indirectly on infection, a major complication that may occur during wound healing. Despite the advances that have been made, the findings from animal studies conducted in rodents may not translate well into clinical trials because of the significant anatomical differences between the skin of humans and rodents. In addition, the mechanisms underlying wound healing in rodents differ considerably from those involved in wound healing in humans. Therefore, using large animal models, such as pigs, which share more similar structural features and wound healing mechanisms with humans may result in better translation into clinical trials. Therefore, the potential of 1,4-dideoxy-4-seleno-D-talitol (SeTal), a selenosugar, was tested in a pig model of wound healing in the studies described in this thesis using 2 different drug carriers, phosphate buffered saline (PBS) and 80% glycerol. Several macroscopic and histopathological aspects of different phases of wound healing were examined in three animal trials. The increasing prevalence of MDR (multi-drug resistance) in bacteria over the past few decades has given rise to concerns about the potential future lack of efficacy of most commercially available antimicrobials. To overcome this global health issue, development of new therapies based on using natural antimicrobials, drug repurposing and drug combination, have gained increasing interest. Drug repurposing or drug repositioning aims to find new applications for existing compounds with established pharmacological and toxicological profiles that are currently used for other clinical purposes. In the studies described in this thesis, two main bioactives of honey, bee glucose oxidase and defensin-1, were expressed in vitro and were examined for their functionality. The defensin-1 and glucose oxidase genes from Apis mellifera were successfully cloned in the pFASTBAC1 vector and were introduced into recombinant baculoviruses using a Bac-to-Bac system in an insect cell line. Both proteins were successfully cloned in a bacmid. Glucose oxidase was successfully expressed, and the activity of the expressed protein was confirmed in vitro using an enzymatic assay. Furthermore, in recent decades manuka honey and its therapeutic properties has resulted in numerous scientific investigations and various clinical trials have been conducted. Manuka honey has attracted particular attention because of its notably greater antimicrobial effects, particularly when compared with other varieties of honey. Antimicrobial activities of seleno-compounds, including SeTal, sodium selenite, seleno-L-methionine and ebselen, in combination with the main bioactive of manuka honey, methylglyoxal (MGO), were examined against some of the most common wound pathogens, S. aureus, E. coli and P. aeruginosa, using in vitro disc diffusion and checkerboard assays. Analyses for synergy were performed using fractional inhibitory concentration index (FICI) and fractional bactericidal concentration index (FBCI) determination. Overall, the pig model used in the studies described in this thesis will potentially contribute to enhanced translation of studies in animal models into successful clinical trials. While the studies suggested that repurposing of seleno compounds and combinational therapy may have potential, there is a need for in vivo studies in animal models and subsequently clinical trials.
-
ItemFormulating curcumin in a biodegradable polymeric composite material: a step towards wound healing applications( 2017)The natural process of wound healing typically consists of four distinct but overlapping phases which include, hemostasis (platelet aggregation and blood clot formation), inflammation (migration of blood cells), proliferation (angiogenesis or blood vessel formation), and remodelling (reorganisation of collagen and scar tissue formation). However, in diabetic patients, this elaborate well-programmed process becomes disrupted, and there is an urgent need for compounds and formulations that can improve wound healing in these cases. A variety of natural components, including curcumin, have been identified as wound-healing agents. Curcumin, is a yellow hydrophobic natural polyphenolic pigment derived from the rhizomes of the herb Carcuma longa, which has been identified as the active principal of turmeric. The inability to efficiently deliver curcumin in a soluble form presents a chief challenge for its clinical use. Here we characterised, and optimised different biodegradable and biocompatible formulations of curcumin encapsulated particles, in order to enhance the efficiency of curcumin wound healing effect. The size of the optimised curcumin particles ranged from 1286 to 1485 nm, with an encapsulation efficiency of 75%. The zeta potential exhibited values in the range of (-7.2) to (-7.96) with the PDI of 0.4. Physical characterisation using TEM imaging ensured the successful fabrication and encapsulation of curcumin in the polymeric matrix, which had been fabricated in rod shape. Release profile occurred in a biphasic manner including an initial burst, followed by a sustained release trend for curcumin particles. In vitro cytotoxicity assays along with microscopic imaging confirmed safety of the applied concentration of curcumin particles below 25 µg/ml. Moreover, the results of cellular uptake study validated the internalisation of curcumin particles. Overall this thesis, elucidated the developed biocompatible and biodegradable formulations for curcumin encapsulation do have the potential to be employed as a drug delivery vehicle for curcumin. Further validation of the potential of this preparation to enhance wound healing is still needed.