Showing items 1 - 4 of 4

Your selections:

Echogenic liposomes for ultrasound-triggered drug delivery

  • Authors: Izuchukwu, Ezekiel Charles
  • Date: 2021-10
  • Subjects: Liposomes , Drug delivery systems , Colon (Anatomy) Cancer Treatment , Transmission electron microscopy , Fourier transform infrared spectroscopy , Liquid chromatography , Echogenic liposomes , Ultrasound-triggered drug delivery
  • Language: English
  • Type: Masters theses , text
  • Identifier: http://hdl.handle.net/10962/188997 , vital:44805
  • Description: Colorectal cancer is one of common cancers worldwide. It is the third most diagnosed cancer and the second leading cause of death. The use of 5-fluorouracil (5-FU) alone or in a chemotherapy regime has been the effective treatment of colorectal cancer patients. The efficacy of 5-FU in colorectal cancer treatment is significantly limited by drug resistance, gastrointestinal, and bone marrow toxicity through high-level expression of thymidylate synthase, justifying a need to improve its therapeutic index. Liposomes are colloidal membranes comprising of one or more lipid bilayers enclosing an aqueous core. They have been used to improve the therapeutic index of many anti-cancer drugs by changing drug absorption, elongating biological half-life, reducing metabolism, and reducing toxicity to healthy tissues. Echogenic liposomes are specifically designed to respond to external triggering like ultrasound stimulation by entrapping a gas or an emulsion that can vaporize. A liposome's unique property is that it can entrap both hydrophobic and hydrophilic substances simultaneously in the lipid bilayer and the aqueous core, respectively. These stimuli-responsive liposomes can be triggered externally with ultrasound, to release the chemotherapeutic cargo only at the required site. This research aims to formulate echogenic liposomes encapsulating 5-FU for potential ultrasound triggered release (echogenic). Liposome formulations wereprepared with lipid composition of crude soybean lecithin and cholesterol by thin-filmhydration method and the drug was passively loaded in the formulation. The 5-FU loadedliposomes were evaluated by dynamic light scattering (DLS) for particle size, polydispersityindex, and zeta potential and transmission electron microscopy (TEM) for morphology.Encapsulated liposomal formulations were also evaluated using physicochemical techniquesincluding thermogravimetric analysis (TGA), differential scanning calorimetry (DSC),Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Theencapsulation efficiency and release kinetics were studied using a validated high-performanceliquid chromatography (HPLC) method. Echogenic properties were explored by entrapping abiocompatible gas (argon) at the same time as the drug (5-FU) using a pressure/freezemethodology. The liposomal formulations were typically spherical with a size of about 150 nmand encapsulation efficiency of 62%. Low-frequency ultrasound (20 kHz) was used to triggerthe drug release from the complete formulation at 10%, 15%, and 20% amplitude and exposuretime of 5 min and 10 min. The rate of drug release from the nano-carrier was a function of theultrasound amplitude and exposure time and reached a maximum of 65% release under theconditions investigated. The cumulative release was investigated, with and without theapplication of ultrasound. It was demonstrated that the application of ultrasound resulted in complete release (99%) after 12 h while this dropped to 70% without ultrasound. These results are encouraging for optimizing ultrasound parameters for triggered and controlled release of the 5-FU, for conditions such as the management of cancer where low-power ultrasound can be applied. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
  • Full Text:
  • Date Issued: 2021-10

Method validation for the quantification of casticin in vitex agnus castus fruit using an ftir multivariate chemometric model

  • Authors: Du Toit Louw, Philippus
  • Date: 2018
  • Subjects: Drugs -- Analysis -- Methodology -- Evaluation , Alternative medicine -- Research , Liquid chromatography
  • Language: English
  • Type: Thesis , Masters , MPharm
  • Identifier: http://hdl.handle.net/10948/30917 , vital:31222
  • Description: The Complementary and Alternative Medicines (CAMS) and dietary supplement industry is an R8.84 billion a year industry in South Africa, with the sector expected to grow 12% annually. The industry has largely been unregulated up until 15 November 2013, when the South African government amended the Medicines and Related Substance Control Act (Act 101 of 1965) to include the definition of “Complementary Medicines” and “Health Supplements”. The emphasis of the new regulations is largely on the quality and safety of CAMS products. Manufacturers therefore need to demonstrate that the active ingredients used in manufacturing will be of an appropriate and consistent quality. The research question therefore is: Can a chemometric multivariate model be used to develop a rapid, cost effective method to quantify casticin, the major chemical constituent of Vitex agnus-castus (VAC) that can be used during routine quality control procedures? The primary aim of this study was to prepare a validated method using fourier transform infrared spectroscopy (FTIR) to quantify the casticin content in VAC fruit. The results from the HPLC analysis were as follows; the penduletin eluted at a retention time of 12.419 ± 0.376 minutes. The casticin eluted at a retention time of 12.943 ± 0.018 minutes. The casticin content for the samples ranged from 0.0115 – 0.0147% m/m casticin content with an average of 0.0134%. This is well below the pharmacopoeia requirement of not less than (NLT) 0.08% casticin content as described in the British Pharmacopoeia (BP). The results obtained from the HPLC analysis were used to construct the FTIR calibration model. The calibration model consisted of 18 spectra with 530 selected data points. The model was specific for casticin as spectral regions in the calibration model can be correlated to a known IR spectral response associated with the carbonyl group of casticin. The calibration equation in the xii form of % m/m casticin content had a coefficient of determination (R2) value of 0.9855 and a root mean square error of cross-validation (RMSECV) of 0.000119. The accuracy of the model had recoveries of between 98 - 102% for the actual vs true prediction. The percentage relative standard deviation (%RSD) between nine repeated measurements was 3.46%, this does not meet the International Conference of Harmonisation (ICH) requirement for precision of not more than (NMT) 2% RSD. The range of the calibration model was between 0.01147 and 0.01469 % m/m casticin content as established by the calibration model. The robustness of the method was assessed by challenging the model with samples that fall outside of the concentration of range of the model. This was established by quantifying previously scanned samples of VAC that is not part of the calibration set. The model was able to verify if the tested samples prediction was outside of the validated calibration range. The method was subsequently also challenged with a sample of a different identity to VAC. The model indicated that the sample tested does not fall in the range of the method and was clearly recognised as an outlier. The method was rapid and does not require any expensive solvents or timeconsuming sample preparation. However, the method does not meet the ICH requirements for method validation, the method does show potential and further method development and expansion of the calibration model can ensure that the method be validated.
  • Full Text:
  • Date Issued: 2018

The chemistry of Algoa Bay ascidians

  • Authors: Bromley, Candice Leigh
  • Date: 2016
  • Subjects: Sea squirts -- South Africa -- Algoa Bay , Marine metabolites , Chemistry, Analytic , Liquid chromatography , Inductively coupled plasma mass spectrometry , Metal ions , Nucleosides , Vanadium
  • Language: English
  • Type: Thesis , Doctoral , PhD
  • Identifier: vital:4560 , http://hdl.handle.net/10962/d1020606
  • Description: This thesis investigates the chemistry of 25 ascidian species collected from Algoa Bay, South Africa with a concerted focus on metal accumulation by these ascidians and the possible interaction of these metals with ascidian metabolites. Chapter 2 details the screening techniques employed to establish the presence of nitrogenous metabolites (1H- 15N HMBC), hyper-accumulated metal ions (ICP-MS) and potential metal ion/ ascidian metabolite complexes (LC-ICP-MS/ESI-MS). Unfortunately, exhaustive attempts to detect intact metal ion/ascidian metabolite complexes through the use of liquid chromatography with parallel inductively coupled plasma mass spectrometry/electrospray mass spectrometry (LC-ICPMS/ ESI-MS) were unsuccessful. However, the LC-ICP-MS/ESI-MS data obtained for the crude organic extracts of six of the Algoa Bay ascidian species, Distaplia skoogi, Aplidium monile, Aplidium sp., Didemnum sp., Leptoclindines sp. and Polycitor sp. enabled identification of a number of ten halogenated metabolites, namely the indoles 2.28-2.30, and the tyramine and tyrosine derivatives (2.31-2.33, 2.41, 2.43, 2.44 and 2.46), within the ascidian extracts. This study confirmed that LC-ICP-MS/ESI-MS is a powerful tool for the dereplication of halogenated metabolites in complex mixtures especially where these compounds are present in very small amounts. This study is also the first report of these compounds (eight of which are known) in African ascidians. Compounds 2.32 and 2.46 have not been reported before from a marine source. Compounds 2.28-2.30 and 2.33 were present in sufficient amounts in the respective ascidian extracts to allow their isolation and structure elucidation using standard spectroscopic techniques Chapter 3 explores the ability of ascidians to accumulate a wide range of metal ions at concentrations which are often orders of magnitude higher than those of the surrounding sea water. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the total ion concentrations of 24 metals in 25 Algoa Bay ascidian species. To the best of our knowledge this is the largest and most extensive investigation of metal concentrations in a group of different ascidians occurring in the same area. Hypotheisizing that the metal ion concentrations for each ascidian specimen screened may represent a unique fingerprint for each specimen principal component analysis (PCA) was used in an attempt to establish whether there were spatial, temporal or phylogenetic relationships associated with the metal concentration fingerprints of the ascidians that formed part of this study. The PCA results showed that there were no statistically significant relationships between ascidian metal ion concentrations and either the collection year or the collection site of the ascidians. However, species from the family Didemnidae provided the clearest statistical evidence supporting a phylogenetic relationship between these ascidians and their hyperaccumulated metal ion profiles. Furthermore, these results suggested that ascidian species are indeed actively concentrating metal ions from the surrounding sea water and are not simply sinks for passively accumulated metal ions. Interestingly, the concentration of vanadium in the set of ascidians studied did not appear to correlate with any of the other metals accumulated by these ascidians suggesting that there is possibly a unique method employed for the accumulation of vanadium by ascidians. Chapter 4 investigated this possibility further after the nucleosides 4.10, 4.11, 4.13, 4.15, 4.17 and 4.40 were isolated from the vanadium accumulating ascidian Aplidium monile. Studies into the interactions between nucleosides and vanadyl are unfortunately rare and usually qualitative in nature with limited information provided about the stability or structures of the complexes formed. The vanadyl accumulating aplousobranch ascidians e.g. Aplidium monile dominated our study of Algoa Bay ascidians therefore providing us with the rationale to investigate the relatively little studied binding ability and stability of vandyl-nucleoside complexes. Potentiometric studies were conducted to determine the stability constants of complexes formed between the oxovanadium ion vanadyl (VO2+) and the commercially available nucleosides 4.10-4.14. The data afforded by this analysis clearly confirmed the complexity of the vanadyl/nucleoside complexation and suggested that guanosine (4.12) formed the most stable complex with oxovanadium ions. We were also able to establish a third protonation constant for the hydroxyl moiety in 4.12 with a logK 8.87 which has not been previously reported. Finally, Chapter 5 revisited the cytoxicity two Algoa Bay ascidians, Clavelina sp. and Atriolum marinense the extracts from which produced promising bioactivity results in previous studies against oesophageal cancer cells. The HP-20 fractionated extracts of Clavelina sp. and Atriolum marinense proved to be similalrly cytotoxic to breast cancer cells. With the exception for the 100% acetone(aq)fractions the NMR data for both species suggested that most active non polar fractions were dominated by what appeared to be structurally unremarkable fatty acid glycerides and as such were not pursued further. Purification of the 100% acetone(aq)fraction of A. marinense resulted in the isolation of a styrene trimer, 5.1, common to both ascidian extracts. The NMR simulation software WIN-DAISY was employed to confirm the structure of 5.1. Attempts to establish if 5.1 was an isolation artefact or a product of marine pollution were inconclusive
  • Full Text:
  • Date Issued: 2016

Analytical procedures for the determination of wattle polyphenols in wastewaters

  • 1
  • Disclaimer
  • Privacy
  • Copyright
  • Contact