dc.contributor.advisor | Youan, Bi-Botti C. | |
dc.contributor.author | Ngo, Albert Nguessan | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018 Spring | |
dc.description | Title from PDF of title page viewed June 17, 2019 | |
dc.description | Dissertation advisor: Bi-Botti C. Youan | |
dc.description | Vita | |
dc.description | Includes bibliographical references (pages 144-173) | |
dc.description | Thesis (Ph.D.)--School of Pharmacy and Department of Chemistry. University of Missouri--Kansas City, 2018 | |
dc.description.abstract | This study is divided into two aims. Aim #1 focuses on the development and
characterization of tenofovir (TFV) loaded a stimuli sensitive nanomedicine against male to
female HIV/AIDS infection. Aim #2 focus on the development of a verstatile formulation for
drug solid dispersion applicable to other anti HIV/AIDS active pharmaceutical agents..
In Chapter 1 and 2, an overview related to the hypothesis to be tested and a literature
review is extensively discussed, respectively. Aim#1 and #2 are summarized in Chapter 3-5
and Chapter 6 respectively.
Pre-exposure propyilaxis (PrEP), using topical TFV based nanomedicine is a promising
effective way to prevent male-to-women HIV/AIDS infection. It is hypothesized that human
prostatic acid phosphatase (hPAP) content in semen can trigger the release of TFV loaded
chitosan /TPP NPs against male to female HIV/AIDS transmission during penile-vaginal
intercourse.
In Chapter 3, a response surface methodology is used to identify the optimal
concentration of 3, 3, 3 trichloroacetic acid (TCA) needed for the efficient quantification of
TFV released interfering with protein containing simulated vaginal and seminal fluids. The
optimal concentration needed to efficiently pellet down protein is 4% w/v (a saddle point). In
these conditions, the limit of detection (LOD) and limit of quantification (LOQ) of TFV are
0.0014 mg/ mL and 0.0042 mg/mL respectively.
In Chapter 4, a method for improving the physico-chemical properties of TFV loaded
chitosan/TPP NPs is engineered using a modified ionic gelation process. The NPs are
characterized for the percent encapsulation efficiency (% EE), size, morphology, release
mechanism and in vitro cytotoxicity. The spherical and nontoxic NPs size and (% EE) range
from 171-379 nm, 86.3-92.7%, respectively. The NPs exhibit a sustained release following
anomalous transport mechanism.
In Chapter 5, the influence of hPAP (50 Unit/mL) on the release of TFV from five
different chitosan/TPP NPs formulations are engineered using the above ionic gelation process.
Formulation (F1) exhibits significant TFV, released in the presence of hPAP considering the
similarity factor and difference factor of 56.5 and 40.3 respectively. The NPs size, % EE, ζ and
PDI are 149.3-8924.67 nm, 78.8-93.71%, 4.15-11.23 mV and 0.256-1 respectively. The
optimal condition for enhanced TFV released from chitosan NPs formulation under the
influence of hPAP compared to the control is obtained for chitosan concentration (1.5 mg/mL),
acetic acid concentration (1.25 % v/v) and TPP concentration (3 mg/mL, TPP being a hPAP
substrate), and TFV amount (5 mg), respectively. This nanoparticle formulation is a promising
topical anti-HIV microbicide for HIV/AIDS prevention.
In Chapter 6, a dual versatile coating process and fast dissolving crystal solid
dispersion is engineered to enhance the aqueous dissolution and dispersion of hydrophobic
drugs. The motivation of this study came from the knowledge gained in the process used to
improve the physico-chemical properties of chitosan NPs. Docetaxel a BCS Class 2 drug is
dissolved in glacial acetic acid/SA solution and subsequently freeze-dried (C-DXT). The
relatively safe C-DXT formulation rapidly forms an aqueous non-rigid nanosuspension (mean
diameter size ~ 161 nm) with a faster drug dissolution rate compared to native DXT. The
difference factor (f1) and the similarity factor (f2) values are 547.8 and 7.1 respectively. This
unique crystal solid dispersion engineering process of DXT using SA might be applicable to
other anti-HIV/AIDS hydrophobic bioactive agents to enhance their safety and efficacy. | eng |
dc.description.tableofcontents | Statement of the problem -- Literature review -- Optimal concentration of 2,2,2-trichloroacetic acid for protein precipitation based on response surface methodology -- Sodium acetate coated tenofovir-loaded chitosan nanoparticles for improved physico-chemical properties -- In-vitro assessment of human acid phosphatase triggering tenofovir release from chitosan/tpp nanoparticles -- Engineering fast dissolving sodium acetate mediated drug crystalline solid dispersion -- Summary and future directions -- Appendices | |
dc.format.extent | xxvi, 174 pages | |
dc.identifier.uri | https://hdl.handle.net/10355/68861 | |
dc.publisher | University of Missouri -- Kansas City | eng |
dc.subject.lcsh | HIV (Viruses) -- Treatment. | |
dc.subject.lcsh | HIV infections -- Prevention | |
dc.subject.lcsh | Drug delivery systems | |
dc.subject.lcsh | Acid phosphatase | |
dc.subject.other | Dissertation -- University of Missouri--Kansas City -- Pharmacy | |
dc.subject.other | Dissertation -- University of Missouri--Kansas City -- Chemistry | |
dc.title | Engineering of Human Acid Phosphatase Enzyme Sensitive Nanomedicine for HIV/AIDS Prevention by Topical Route | eng |
dc.type | Thesis | eng |
thesis.degree.discipline | Pharmaceutical Sciences (UMKC) | |
thesis.degree.discipline | Chemistry (UMKC) | |
thesis.degree.grantor | University of Missouri--Kansas City | |
thesis.degree.level | Doctoral | |
thesis.degree.name | Ph.D. (Doctor of Philosophy) | |