Disputats.

Thesis (Ph.D)--Chemical Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Rousseau, Ronald; Committee Member: Meredith, Carson; Committee Member: Prausnitz, Mark; Committee Member: Teja, Amyn; Committee Member: Wilkinson, Angus. Part of the SMARTech Electronic Thesis and Dissertation Collection.

This report accounts the experience of a faculty member’s intention of creating an innovative interactive learning simulation in the field of pharmacokinetics to support the faculty member’s teaching and addresses his students’ learning needs. The report also describes the collaboration process between the faculty member and the instructional technology support units through the different phases of design, development, implementation and assessment on the simulation. It also discusses a faculty member’s role in using technology to enhance teaching and learning under university context. / text

published_or_final_version / Biochemistry / Master / Master of Philosophy

No description available.

The aim of this study is to determine how Volume of Distribution (VD) – one of the main characters of pharmacokinetic data is obtained, what methods are used, how reliable values they give, and a new computational QSAR algorithm for prediction of VD is built and discussed. The development of a new drug estimated total time of more than 14 years with investment exceeding U$900 million in 1990-ies up to €1 billion in 2000. Studies show that elimination of new developed drugs from the last stage screening process or even withdrawal from market usually is a result of poorly predicted pharmacokinetic data. The main goal of our study was to build a new computational algorithm for prediction of VD that would result in lessened cost and time consumption. The prediction of VD using quantity-structure activity relationship (QSAR) method the algorithm shows VD values statistically better than obtained in other methods of. We based experimental algorithm on 760 values of VD compiled from literature, original articles, and Internet databases and proved data quality as 'Good', 'Moderate', 'Bad' or 'Very bad'. We investigated literature sources to have data mostly after intravenous bolus administration of the drug, VSS, and tested the algorithm on 96 more newly obtained drug VD values that were not included in building the computational algorithm. Mean fold error for Training Set was 1,87, and 2,08 for Testing Set. We built and concluded the module to be good for prediction of VD for acid... [to full text]

The objectives of this study were to characterize the ocular and systemic adverse effects, and systemic pharmacokinetics of topical 0.1% diclofenac. This was investigated in 8 healthy cats using a blinded, randomized, placebo-controlled, cross-over design. Drops were administered bilaterally 4 times daily for 7 days. Ocular, hepatic and renal variables were measured at various timepoints. Pharmacokinetic sampling occurred on Days 1 and 7. Treated animals were 8 times more likely to develop conjunctival hyperemia than control animals (p=0.0161). Pharmacokinetic analysis showed that accumulation occurs with repeated dosing. Topical 0.1% diclofenac treatment did not have any significant effect on hepatic or renal function, other than reduction GFR in the second phase of the study (p=0.0013). In conclusion, topical 0.1% diclofenac appears to be safe in healthy cats causing only mild ocular irritation. Careful patient selection may be indicated as systemically-absorbed diclofenac may be associated with reduction in GFR in volume-contracted states. / Ontario Veterinary College Pet Trust Fund

Nanomaterial toxicity is a major concern and could potentially hamper the progress of biomedical nanotechnology development. Dispelling these concerns requires that the consequences of nanomaterial exposure are evaluated, and the findings will determine whether developmental hurdles can be overcome. This thesis evaluates the both in vivo and in vitro impact of quantum dots (QD , zinc sulphide capped cadmium selenide semiconductor nanocrystals) a fluorescent nanoparticle label with potential as an optical in vivo imaging agent. This work reviews nanoparticle characterization techniques and their importance to biological responses, and surveys QD interactions both in vivo and in vitro. We collected pharmacokinetic and toxicity data by a) quantitatively surveying the in vivo absorption, distribution , metabolism and excretion of QDs, and b) measuring the impacts of QDs on relevant organs (in vivo) and cells (in vitro). Neither of these areas had been explored when this thesis was started. In vivo, intravenous QD dosing in Sprague-Dawley rats showed uptake into reticuloendothelial cells with surface coating dependent kinetics, slow degradation, no excretion detected in feces or urine, and no indications of toxicity. The liver took up the majority of dose after 90 minutes and small amounts of QDs appeared in the spleen, kidney, and bone marrow. After 30 days, the cadmium concentration in the kidneys increased to 3µg/g without a proportional amount of zinc, indicating QD breakdown. In vitro we noted phagocytic capacity comparable to in vivo results, QD breakdown, and a retention of normal macrophage function thereby demonstrating that primary rat liver macrophages (Kupffer cells) are an appropriate in vitro system with which to investigate the cellular responses to quantum dots. Such an in vitro model will facilitate faster evaluation of individual nanotechnologies intended for in vivo use. This dissertation addresses a lack of in vivo background information needed to understand the consequences of QD exposure; though QD fail to demonstrate pharmacokinetics desirable for in vivo imaging agents, they are not toxic. Importantly, we provide in vitro data that will lead to the development of accurate and efficient in vitro primary screening methods that will be central to the further development of biomedical nanotechnologies.

Nanomaterial toxicity is a major concern and could potentially hamper the progress of biomedical nanotechnology development. Dispelling these concerns requires that the consequences of nanomaterial exposure are evaluated, and the findings will determine whether developmental hurdles can be overcome. This thesis evaluates the both in vivo and in vitro impact of quantum dots (QD , zinc sulphide capped cadmium selenide semiconductor nanocrystals) a fluorescent nanoparticle label with potential as an optical in vivo imaging agent. This work reviews nanoparticle characterization techniques and their importance to biological responses, and surveys QD interactions both in vivo and in vitro. We collected pharmacokinetic and toxicity data by a) quantitatively surveying the in vivo absorption, distribution , metabolism and excretion of QDs, and b) measuring the impacts of QDs on relevant organs (in vivo) and cells (in vitro). Neither of these areas had been explored when this thesis was started. In vivo, intravenous QD dosing in Sprague-Dawley rats showed uptake into reticuloendothelial cells with surface coating dependent kinetics, slow degradation, no excretion detected in feces or urine, and no indications of toxicity. The liver took up the majority of dose after 90 minutes and small amounts of QDs appeared in the spleen, kidney, and bone marrow. After 30 days, the cadmium concentration in the kidneys increased to 3µg/g without a proportional amount of zinc, indicating QD breakdown. In vitro we noted phagocytic capacity comparable to in vivo results, QD breakdown, and a retention of normal macrophage function thereby demonstrating that primary rat liver macrophages (Kupffer cells) are an appropriate in vitro system with which to investigate the cellular responses to quantum dots. Such an in vitro model will facilitate faster evaluation of individual nanotechnologies intended for in vivo use. This dissertation addresses a lack of in vivo background information needed to understand the consequences of QD exposure; though QD fail to demonstrate pharmacokinetics desirable for in vivo imaging agents, they are not toxic. Importantly, we provide in vitro data that will lead to the development of accurate and efficient in vitro primary screening methods that will be central to the further development of biomedical nanotechnologies.

The central hypothesis of the dissertation is that “the design and synthesis of a codrug of an opiate and a cannabinoid can be achieved which is stable in the gastrointestinal tract and shows a superior pharmacological and pharmacokinetic profile when compared to a physical mixture of the two parent drugs.” To prove the hypothesis, a series of novel codrugs were prepared by conjugation of the opiate drug codeine with Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol, abn-cannabidiol and an opiate prodrug 3-O-acetylmorphine with Δ9-THC. Codeine-cannabinoid codrugs were evaluated for analgesic activity in the rat after oral administration. The Cod-THC codrug showed greater effectiveness as well as prolonged pain management properties as compared to the parent drugs. The stability of Cod-THC codrug in aqueous solutions from pH 1-9, in simulated gastrointestinal fluids, in brain homogenate and the hydrolysis of the carbonate ester linkage in rat plasma suggested that after oral administration, the codrug would be absorbed intact from the GI tract and then hydrolyze in the plasma to generate both parent drugs. The enzymes present in rat brain homogenate were incapable of cleaving the codrug into the parent drugs. The pharmacokinetic profiles of the Cod-THC codrug and an equimolar physical mixture of the parent drugs were evaluated in rats. The plasma concentrations of codeine and Δ9-THC were much higher after codrug administration compared to the plasma concentrations of these drugs after oral administration of an equimolar physical mixture. The parent drugs were also present in the plasma for longer period of time compared to the physical mixture, probably due to the sustained release of the parent drugs from codrug in the plasma. The concentrations of codeine and Δ9-THC were much higher in rat brain after oral administration of the Cod-THC codrug as compared to brain concentrations of these drugs after oral administration of the physical mixture. Thus, the design and synthesis of an opiate and a cannabinoid codrug was achieved which was stable in the gastrointestinal tract, showed enhanced analgesic effects as compared to the parent drugs, and also showed a superior pharmacokinetic profile when compared to a physical mixture or the two parent drugs.