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Engineering of Human Acid Phosphatase Enzyme Sensitive Nanomedicine for HIV/AIDS Prevention by Topical Route
Başlık:
Engineering of Human Acid Phosphatase Enzyme Sensitive Nanomedicine for HIV/AIDS Prevention by Topical Route
Yazar:
Ngo, Albert Nguessan, author.
ISBN:
9780438023925
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (200 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Bi-Botti Celestin Youan Committee members: William Gutheil; Kathleen Kilway; Jacob Marszalek; James Murowchick.
Özet:
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, 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.
Notlar:
School code: 0134
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
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