Massey Documents by Type

Permanent URI for this communityhttps://mro.massey.ac.nz/handle/10179/294

Browse

Has files: YesSubject: search.filters.subject.Drug delivery systems

Search Results

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Novel collagen-based wafers as a drug delivery method for local analgesia in deer antlers : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Sciences at Massey University, Manawatu, New Zealand
    (Massey University, 2021) Sahebjam, Farzin
    Introduction This study provided a practical and novel solution for post-operative pain mitigation and wound management after velvet antler removal in red deer (Cervus elaphus). Currently, there are no topical methods to mitigate pain for an extended period of time in deer following surgical removal of antlers. The current methods licensed in New Zealand provide only peri-operative analgesia with short-term effects and raise animal welfare concerns about whether animals are still in pain when the effect has worn off, especially in the deer industry in which a large number of animals are being managed. Materials and methods In vitro study: In vitro drug release test (IVDRT) was conducted using the Franz diffusion cell to assess the drug release rates of lidocaine and bupivacaine in two different phases of the pilot and main studies. The pilot in vitro study contained 9 treatment groups and 3 control groups (n=3), which were classified based on collagen extraction technique, whether modified with zinc oxide-polyvinylpyrrolidone (ZnO-PVP) nanoparticles and the difference in the order of adding local anaesthetics and ZnO-PVP nanoparticles. The main in vitro study was comprised of 4 treatment groups of 5%, 10%, and 25% ZnO-PVP nanoparticles (n=6) proportional to dry collagen weight and a control group. In both pilot and main in vitro studies, the samples were taken every 15 minutes in the first hour and every 2 hours up to 12 hours. LC-MS and HPLC were used for the quantification of the samples in the pilot and main in vitro studies, respectively. MNT validation study: Forty male deer (stags) were assigned for the MNT validation study on three alternative days. A handheld algometer (Wagner FPX50) was used for mechanical nociceptive threshold (MNT) assessment of four antler sites (cranial, medial, caudal, lateral) in both right and left antlers. Animal body weight (kg) and antler length (cm) were recorded to investigate the correlation with MNT. The MNT readings from three days were compared with each other. In addition, the MNT reading from all four antler sites and the right and left antlers were compared with each other. In vivo study: Eighteen stags sorted into three groups of 6 animals in each (2 treatment groups and 1 control group) for the pilot in vivo study, and forty yearling age stags assorted into four groups of 10 animals (three treatments and one control), were used in the main in vivo study. All animals had both antlers removed after administration of local anaesthesia. The control group in both pilot and main in vivo studies received a ring block of 4% articaine hydrochloride only, whilst the treatment groups received modified (with ZnO-PVP) or non-modified collagen composite wafers to the wound sites. The modified collagen composite wafers had 50% ZnO-PVP for the pilot in vivo study and had 0%, 5% or 25% ZnO-PVP proportional to dry collagen weight for the main in vivo study. A handheld algometer (Wagner FPX50), was used for mechanical nociceptive threshold (MNT) assessment at different time points (0, 4, 24, 72 hrs, 7 days and 14 days). Thermal imaging with a forward-looking infrared (FLIR) camera was performed for the detection of temperature differences between the groups. Digital photography of the wounds was performed for further quantitative wound healing analysis. Pharmacokinetic study: Blood samples were drawn from deer after the application of collagen composite wafers at time points t0, t1, t2, t4, t6, t8, t12, and t24 hours for the pilot study and at time points t0, t1, t2, t4, t6, t8, and t24 hours for the main in vivo study. The plasma was iv analysed with LC-MS to calculate pharmacokinetic parameters with the non-compartmental method such as Cmax, Tmax, AUC, AUMC, half-life, the volume of distribution and clearance. Statistical analysis: Higuchi model was mainly incorporated to calculate drug release rates for the in vitro studies. For in vivo studies, the statistical analyses were performed with a linear model for repeated measurements that accounted for the fixed effects of day, antler, location within antler or antler sites, antler length and weight of deer as covariates, and the random effect of animals. Results IVDRT did not show any statistically significant difference between the treatment groups; however, the treatment groups had significantly slower release compared to the control group in the pilot in vitro study. IVDRT in the main in vitro study showed the slowest release rate in the treatment group with 25% ZnO-PVP compared to the other groups for both lidocaine and bupivacaine. The control group had the most rapid drug release rates compared to the treatment groups, particularly for lidocaine. Furthermore, lidocaine showed a considerably slower release compared to bupivacaine when zinc oxide nanoparticles were incorporated, and the results significantly differed. MNT validation results showed that antler length (cm) and animal body weight (kg) are directly and positively correlated with the baseline MNT readings. The MNT readings from four sites of antlers, including cranial, medial, caudal and lateral aspects, did not have any significant difference from each other. In addition, the MNT readings from the right and left antlers did not show any significant difference from each other. In vivo results in the pilot study showed a lack of collagen composite wafer adherence for the non-modified wafers (PT2) and 50% adherence for the modified wafers (PT1) in the pilot study. As a result of the main in vivo study, 90%, 70%, and 45% were in group 25%NP (T1), 5%NP (T2), and 0%NP (T3) to the wounds, respectively. A significant difference was observed in the recovery rates of PT1 compared to the control group (P<0.0001) for the pilot study. For the main in vivo study, all three treatment groups also showed a significant difference compared to each other: T1 vs. T2 (P<0.01), T1 vs. T3 (P<0.05), and T2 vs. T3 (P<0.0001). In addition, the treatment groups showed a significantly slower recovery rate from analgesia compared to the control group (P<0.0001 for all). All the treatment groups in the main study demonstrated analgesia beyond 6 hrs and up to 10 hrs. The pharmacokinetics study showed significantly smaller Cmax for T1 and T2 compared to T3 only for bupivacaine. Tmax showed significantly smaller values for T1 compared to T2 for only bupivacaine. Both AUC (0-24), AUC (0-∞), and AUMC (0-∞) showed smaller values for T1 and T2 compared to T3. Conclusion The physically modified collagen composite wafer with zinc oxide-PVP nanoparticles, containing a short-acting (lidocaine) and a long-acting (bupivacaine) local anaesthetic, is a novel method to sustain drug delivery of local anaesthetics after the surgical removal of velvet antlers. Our suggested treatment can deliver analgesia to the wounded antler for up to 10 hours and is a safe and convenient method to use by farmers in the deer industry. Furthermore, the collagen wafer is very adhesive to the wound and can help facilitate wound healing of deer antlers.
  • Thumbnail Image
    Item
    An investigation into nanocellulose based hydrogels for analgesic treatment of avian species : thesis presented in partial fulfilment of the requirements for the degree of Master of Science, Chemistry, Massey University, Palmerston North, New Zealand
    (Massey University, 2018) Allan, David Bruce
    Drug delivery techniques are an integral component in modern medical practices. Numerous drugs have been designed to exploit drug delivery systems, primarily oral administration, as it is preferred by the public for treatment of animals and humans. Butorphanol is a commonly used opioid analgesic drug for pain relief in avian species. The pharmacokinetic reports on butorphanol suggest that it is metabolised and cleared from an avian body at a much faster rate when compared to mammals. A single intravenous injection of butorphanol at 2 mg/kg provides analgesia for only 2 hours. When given at higher doses, butorphanol starts to produce side effects such as hyperventilation, cardiac insufficiency, coma and death. Therefore, there is a need to develop a slow release drug delivery system for butorphanol which can prolong the duration of analgesia without the side effects.
  • Thumbnail Image
    Item
    Ionically cross-linked alginate hydrogels as drug delivery systems for analgesics in broiler chickens : thesis presented in partial fulfilment of the requirement for the degree of Masters of Science in Chemistry at Massey University, Palmerston North, Manawatu, New Zealand
    (Massey University, 2017) Booty, Samuel James
    Treating birds with analgesic drugs requires continuous injections of near lethal concentrations to maintain the therapeutic dose in the blood plasma. This is due to birds having higher metabolic rates than mammals. Therefore, there is a need to develop drug delivery systems that can control and slow down the release of analgesics in birds. This study was designed to analyse the sustained release of the model analgesics, sodium salicylate and sodium aspirin, from ionically cross-linked alginate hydrogels, in in vitro and in vivo experiments using broiler chickens as the model bird. Analgesic loaded hydrogels separated into two layers, unlike the homogeneous blank hydrogels. This was labelled as the separation effect. Swelling studies indicated the absence of the insoluble cross-linked alginate material in the hydrogels where the separation effect occurred, with most of the hydrogels dissolving back into the medium. The highest equilibrium swelling percentage achieved in the loaded hydrogels was 68 %. In comparison, the highest equilibrium swelling percentage in the blank hydrogels was 622 %. In vitro drug release profiles showed that the hydrogels released up to 100% of the sodium salicylate within 3.33 hours. In contrast, the hydrogels containing sodium aspirin released only 35 % of the encapsulated drug. Hydrogels containing a drug concentration of 150 mg/mL were injected into the model birds at a dose rate of 150 mg/Kg. No chicken reacted negatively to the hydrogel injection. In vivo results indicate sustained release of the model analgesic from the hydrogels compared to the release from the aqueous solutions of the drug. The effective concentration for an analgesic effect of sodium salicylate was maintained by the group injected with an aqueous solution of sodium salicylate 18 hours after the injection. The groups injected with the hydrogel with the maximum calcium chloride content saw the largest sustained release, with the plasma concentration of sodium salicylate remaining over the effective concentration for up to 36 hours after the injection. Keywords: Sodium salicylate, sodium aspirin, hydrogel, analgesia, sustained release, broiler chicken.
  • Thumbnail Image
    Item
    Stimuli sensitive polysaccharide based hydrogels as colon targeted drug delivery vehicles : a thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry, Massey University, Turitea campus, Palmerston North, New Zealand
    (Massey University, 2014) Kavianinia, Iman
    Administering drugs orally is by far the most widely used route of administration that will help eliminate the pain caused by injection, psychological barriers associated with multiple daily injections and possible infection from injection sites. However, it is important for oral drug administration to overcome several different obstacles during the delivery through the gastrointestinal tract. The barriers can be morphological barriers and physiological factors such as a wide range of pH and enzymatic activities. The lower water content and fluid mobility of the colon, which leads to longer retention times and also lower proteolytic activity of colon compared to other areas of the gastrointestinal tract, make the colon an ideal site for both systemic and local delivery of drugs. Therefore aggressive research efforts have recently focused on development of new strategies for delivering drugs to the colon. As a drug delivery systems, hydrogels have received increasing attention due to their outstanding merits. Among the various hydrogels, including natural, synthetic and natural/synthetic hybrid hydrogels, chitosan has attracted significant attention in a broad range of pharmaceutical and biomedical applications. Chitosan is a hydrophilic polyelectrolyte heteropolysaccharide composed of randomly (1→4)-linked 2- acetamido-2-deoxy-β-D-glucopyranose and 2-amino-2-deoxy-β-D-glucopyranose linked by (1→4)-β-glycosidic bonds. Unlike most known bioadhesive polymers, chitosan displays unique pharmaceutical and biomedical applications due to the large number of hydroxy and amino groups on the backbone of chitosan. These functional groups can be readily modified. This study was commenced with the aim of engineering a carrier with high enough physicochemical stability to reach the colon and to be able to protect a drug from various obstacles throughout the gastrointestinal tract. In this study, a new generation of chitosan derivatives was developed. Furthermore, their viability was investigated for potential applications as drug carriers to the colon. Chitosan based films with improved physical properties from introducing a cyclic imide moiety into the chitosan matrices was developed and characterised. Mechanical, thermal and chemical analyses of these films show that the heterocyclic imide linkage imparts excellent thermal, mechanical and chemical stability to the chitosan film. Additionally, spray dried chitosan microspheres with improved mechanical stability were examined for the controlled drug release of bovine serum albumin as a model protein drug. Additionally, a novel generation of amphoteric crosslinked chitosan derivatives was designed to be pH sensitive and bacterially degradable. Tabletted carriers were designed to protect the drug from the harsh acidic environment of the stomach and the rigorous enzymic activity of the small intestine and deliver the drug to the colon. Tabletted formulation forms of these novel amphoteric derivatives of chitosan showed the excellent potential formulations as colon specific drug delivery vehicles.