PhD Theses
http://repository.aust.edu.ng/xmlui/handle/123456789/353
This sub-community contains all PhD thesis of the five streams offered at AUSTFri, 19 Jul 2024 02:09:05 GMT2024-07-19T02:09:05ZLaser Induced Heating of Polymer Nanocomposites for Hyperthermia in the Treatment of Triple Negative Breast Cancer
http://repository.aust.edu.ng/xmlui/handle/123456789/5146
Laser Induced Heating of Polymer Nanocomposites for Hyperthermia in the Treatment of Triple Negative Breast Cancer
Onyekanne, Maria Chinyerem Euphemia
The work presents the results of an experimental and computational study of the effects of laser-induced heating provided by magnetite polymer-based nanocomposite structures that are being developed for the localized laser-induced hyperthermic treatment of triple-negative breast cancer. Magnetite nanoparticle-reinforced polydimethylsiloxane (PDMS) nanocomposites were fabricated with weight percentages of (1 %, 5 %, and 10 %) magnetite nanoparticles. The fabricated nanocomposites were exposed to incident Near Infrared (NIR) laser beams with well-controlled powers to generate specific elevated temperatures at different times. The mechanical and thermal properties of the different PDMS-based nanocomposites were critically studied. This was because the unique characteristics during the laser-nanocomposite interactions were driven by the both thermal, microstructural, and physicochemical properties (mechanical properties) of the PDMS-based nanocomposites. Under in vitro conditions, our results from the laser-nanocomposites interactions show a decrease in the cell viability of triple-negative breast cancer cells (MDA-MB-231). Using an ex vivo chicken tissue, laser-nanocomposites interactions resulted in well-controlled temperatures in the hyperthermia domain (41 °C and 44°C) in a submillimeter range using a chicken tissue model. Interestingly, laser irradiation and interaction with the nanocomposites did not cause any observed physical damage to the chicken tissue but resulted in significant breast cancer cell dead. The potential in vivo performance of the PDMS nanocomposites was also investigated using computational finite element models of the effects of laser-magnetite nanocomposites interactions on the temperatures and thermal doses experienced by tissues that surround the nanocomposites devices. The outcomes of the experimental studies were validated using the results from the computational analyses. The implications of the results are discussed for the potential design of plasmonic/magnetic-based nanocomposites devices with attractive combinations of mechanical, structural, and thermal properties that are relevant to laser hyperthermia and photo-thermal-ablation for the localized treatment of triple-negative breast cancer tissue.
Main Thesis
Sat, 02 Jul 2022 00:00:00 GMThttp://repository.aust.edu.ng/xmlui/handle/123456789/51462022-07-02T00:00:00ZBiosynthesis of Gold Nanoparticles for Breast Cancer Targeted Drug Delivery
http://repository.aust.edu.ng/xmlui/handle/123456789/5145
Biosynthesis of Gold Nanoparticles for Breast Cancer Targeted Drug Delivery
Dozie-Nwachukwu, Stella Obiageli
Although there have been significant efforts in breast cancer treatment over the past many decades, current therapeutic approaches are limited by non-specific systemic distribution, inadequate drug concentrations reaching the tumor and multidrug resistance. This dissertation presents the results of experimental and theoretical studies of the potential applications of biosynthesized gold nanoparticles (AuNPs) and micro encapsulated prodigiosin in targeted drug delivery for the treatment of breast cancer. Gold nanoparticles possess unique physicochemical properties, such as large surface area to mass ratio, and high surface reactivity, presence of surface plasmon resonance (SPR) bands, biocompatibility and ease of surface functionalization, which enables them to diffuse with greater ease inside the tumor cells delivering a high amount of drug selectively to tumor cells with significant reduced toxicity. In this work, the biosynthesis of gold nanoparticles (AuNPs) from plant (Nauclea latifolia) and bacteria (Serratia marcescens) were elucidated. The Nauclea latifolia extract was used to synthesize AuNPs in a record time of < 30 sec, and the sizes of the nanoparticles were in the range of 10 nm – 60 nm. The AuNPs were characterized with UV-visible (UV-Vis) spectroscopy, while the nanoparticle shapes, sizes
and polydispersity were elucidated via transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. Selected area electron diffraction (SAED) patterns of the AuNPs showed the four-fringe pattern of gold nanoparticles, which corresponds to the face centered cubic (fcc) metal structure of gold ((111), (200), (220), (311)), which confirmed the formation of pure metallic gold nanoparticles. The biosynthesized nanoparticles were functionalized with some molecular recognition units (MRU) (Luteinizing Hormone Releasing Hormone, LHRH and Folic Acid), through thiol linkages or carbodiimide chemistry. The adhesion force between LHRH- or Folate- conjugated AuNPs and the breast cancer cell line iv MDA-MB-231 was determined through atomic force microscopy (AFM). Furthermore, Helium Ion Microscopy (HIM) was used to visualize the clear ring of attachment of the ligands to the gold core. The encapsulation of prodigiosin in chitosan microspheres was equally studied for localized drug delivery. The water-in-oil emulsion technique in which glutaraldehyde was used as a cross-linker was adopted. The morphologies of the resulting microspheres were then studied using scanning electron microscopy (SEM). The average sizes of the microspheres were between 40 µm and 60 µm, while the percentage yields were found to be between 42±2% and 55.5±3%. The resulting encapsulation efficiencies were between 66.7±3% and 90±4%. The in- vitro drug release from the microspheres were characterized using Higuchi and Korsmeyer-Peppas models.
The implications of these results are then discussed with a view of developing suitable drug delivery systems that will go a long way to solving the problem of breast cancer in the world, with particular reference to Africa.
Main Thesis
Tue, 13 Dec 2016 00:00:00 GMThttp://repository.aust.edu.ng/xmlui/handle/123456789/51452016-12-13T00:00:00ZPolymer-Based Drug Delivery Systems for the Targeted and Controlled Release of Cancer Drugs in Triple-Negative Breast Cancer (TNBC) Treatment
http://repository.aust.edu.ng/xmlui/handle/123456789/5142
Polymer-Based Drug Delivery Systems for the Targeted and Controlled Release of Cancer Drugs in Triple-Negative Breast Cancer (TNBC) Treatment
Jusu, Sandra Musu
Cancer is a disease that exists globally. Among women, breast cancer is most prevalent. Breast cancer exhibits different degrees of aggressiveness. Triple-Negative Breast Cancer (TNBC), which accounts for approximately twenty percent of breast cancer cases, is one of the most aggressive types of breast cancer, and it disproportionately affects women of African and Hispanic origins. Because TNBC is characterized by lack of expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor 2 receptors (HER2), all of which are essential targets for established hormonal therapies and anti-HER2 agents, it is difficult to treat. Currently, conventional methods such as chemotherapy and radiation are used to treat TNBC. Those treatment methods, however, are not very effective because they lack specificity, and they are undesirable due to their high dose requirement, low therapeutic indices, poor bioavailability, and other adverse side effects. To improve TNBC treatment outcomes, therefore, it is essential to explore and develop targeted cancer drug delivery systems that pass muster where current, conventional TNBC treatment methods fail. This thesis, part of which has been published, encapsulates the use of materials science and engineering approaches to develop targeted drug
delivery systems for controlled and localized treatment of TNBC. The thesis contains six chapters. Chapter one covers the introduction, and chapter two covers the literature review. Chapter three discusses the results of an in vitro and in vivo study of a unique blend of polymers [poly (lactic co-glycolic acid) - polyethylene glycol] microspheres that encapsulated LHRH-conjugated and unconjugated drugs, respectively. Chapter four highlights the use of poly (lactic-co-glycolic acid) – chitosan – polyethylene glycol microspheres encapsulating model anti-cancer drugs [prodigiosin and paclitaxel] for controlled drug delivery in TNBC treatment. Chapter five presents the results of a combined experimental and analytical in vitro and in vivo study of blended FDA-approved polymers [poly (lactic-co-glycolic acid), polyethylene glycol, and polycaprolactone] with the potential for sustained localized cancer drug release. Chapter six contains conclusions and suggestions for future work.
Main Thesis
Sun, 05 Sep 2021 00:00:00 GMThttp://repository.aust.edu.ng/xmlui/handle/123456789/51422021-09-05T00:00:00ZAlgorithms For Approximation of J-Fixed Points of Nonexpansive - Type Maps, Zeros of Monotone Maps, Solutions of Feasibility and Variational Inequality Problems
http://repository.aust.edu.ng/xmlui/handle/123456789/5121
Algorithms For Approximation of J-Fixed Points of Nonexpansive - Type Maps, Zeros of Monotone Maps, Solutions of Feasibility and Variational Inequality Problems
Nnakwe, Monday Ogudu
It is well known that many physically significant problems in different areas of research can be transformed at equilibrium state into an inclusion problem of the form 0 ∈ Au, where A is either a multi-valued accretive map from a real Banach space into itself or a multi-valued monotone map from a real Banach space into its dual space. In several applications, the solutions of the inclusion problem, when the map A is monotone, corresponds to minimizers of some convex functions. It is known that the sub-differential of any convex function, say g, and denoted by ∂g is monotone, and for any vector, say v, in the domain of g, 0 ∈ ∂g(v) if and only if v is a minimizer of g. Setting ∂g ≡ A, solving the inclusion problem, is equivalent to finding minimizers of g. The method of approximation of solutions of the inclusion problem 0 ∈ Au, when the map A is monotone in real Banach spaces, was not known until in 2016 when Chidume and Idu [52] introduced J-fixed points technique. They proved that the J-fixed points correspond to zerosof monotone maps which are minimizers of some convex functions. In general, finding closed form solutions of the inclusion problem, where A is monotone is
extremely difficult or impossible. Consequently, solutions are sought through the construction of iterative algorithms for approximating J-fixed points of nonlinear maps. In chapter three, four and seven of the thesis, we present a convergence result for approximating zeros of the inclusion problem 0 ∈ Au.
Let H1 and H2 be real Hilbert spaces and K1, K2, · · · , KN , and Q1, Q2, · · · , QP , be nonempty, closed and convex subsets of H1 and H2, respectively, with nonempty intersections K and Q, respectively, that is,
K = K1 ∩ K2 ∩ · · · ∩ KN ̸= ∅ and Q = Q1 ∩ Q2 ∩ · · · ∩ QP ̸= ∅. Let B : H1 → H2 be a bounded linear map, Gi : H1 → H1, i = 1, · · · , N and Aj : H2 → H2,
j = 1, · · · , P be given maps. The common split variational inequality problem introduced by vi Censor et al. [32] in 2005, and denoted by (CSVIP), is the problem of finding an element u ∗ ∈ K for which ( ⟨u − u∗ , Gi(u∗)⟩ ≥ 0, ∀ u ∈ Ki, i = 1, 2, · · · , N, such that ∗ = Bu∗ ∈ Q solves ⟨v − v ∗ , Aj (v∗ )⟩ ≥ 0, ∀ v ∈ Qj
, j = 1, 2, · · · , P. The motivation for studying this class of problems with N > 1 stems from a simple observation that if we choose Gi ≡ 0, the problem reduces to finding u ∗ ∈ ∩N i=1Ki , which is the known convex feasibility problem (CFP) such that Bu∗ ∈ ∩P j=1V I(Qj , Aj ). If the sets Ki are the fixed
point sets of maps Si : H1 → H1, then, the convex feasibility problems (CFP) is the common fixed points problem(CFPP) whose image under B is a common solution to variational inequality problems (CSVIP). If we choose Gi ≡ 0 and Aj ≡ 0, the problem reduces to finding u ∗ ∈ ∩N i=1Ki such that the point
Bu∗ ∈ ∩P j=1Qj which is the well known multiple-sets split feasibility problem or common split feasibility problem which serves as a model for many inverse problems where the constraints are imposed on the solutions in the domain of a linear operator as well as in the range of the operator. A lot of research interest is now devoted to split variational inequality problem and its gener-alizations.In chapter five and six of the thesis, we present convergence theorems for approximating solu-tions of variational inequalities and a convex feasibility problem; and solutions of split varia-tional inequalities and generalized split feasibility problems.
Main Thesis
Fri, 05 Jul 2019 00:00:00 GMThttp://repository.aust.edu.ng/xmlui/handle/123456789/51212019-07-05T00:00:00Z