Novelty processing and smart delivery of Ganoderma Lucidum spores - PhDData

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Novelty processing and smart delivery of Ganoderma Lucidum spores

The thesis was published by Riahi (née Bharath), Anouska, in December 2022, UCL (University College London).

Abstract:

In recent decades the traditional Chinese medicinal mushroom Ganoderma lucidum (GL), a fungal specie
widely consumed homoeopathically in the Eastern Hemisphere, has been studied particularly with respect
to antitumour and immunoenhancing effects. Research into the various claims however remains limited
owing to the lack of quality and consistency across investigations. As such, efficacy and feasibility of scaleup has not been evaluated in a way that allows widespread consumption or approved treatment. This
project tackles three aspects of drug development from Ganoderma lucidum: Biocompound extraction,
healthcare evaluation via in-vitro testing, and encapsulation for smart delivery. These avenues are brought
together for the first time to evaluate the prospects of developing GL for effective and safe healthcare.
This research investigates the parameters that would influence the extractability of a biocompound from
the spores of Ganoderma lucidum (GLS), via two conventional methods: Hot Water Extraction (HWE) and
Ultrasound-Assisted Extraction (UAE). They are evaluated with respect to their crude water-soluble
polysaccharide yield (GLPS). Solvent polarity and process duration were statistically significant factors
affecting extract yield, with both extraction methods showing considerable gains over similar setups in
literature, recovering over 6% crude GLPS using shorter durations and lower temperatures than other
published investigations. This investigation highlighted the importance of solvent viscosity on specific DGlucan extraction in the GLPS yield. Bioactive effects of the extract were evaluated via cytotoxicity toward
Human Osteosarcoma (HOS) cells in-vitro, achieving over 40% cell growth inhibition. Cytotoxicity however
was only achieved when water-insoluble fractions were administered – suggesting cytotoxicity was a result
of the unextracted crude triterpenoids (GLTP) containing Ganoderic Acids. Therefore, HOS-inhibitory
capabilities are then compared to a GLPS extract containing Ganoderic Acids (in this work termed “PSGA”),
extracted using HWE subject to supervised machine learning optimisation. As well as determining that this
yield was maximised at the longest HWE duration and smallest solvent volume, it was observed to inhibit
HOS growth by nearly 58% after 24 hours. Low doses and shorter incubation were most effective –
suggesting concepts such as resistance (clonal selectivity) and delayed apoptosis, but further work will
verify the reported effects of PSGA dosage and exposure time on cancer proliferation. Lastly, research
effort is devoted to creating an alginate matrix for the controllable delivery of GLS using
Electrohydrodynamic Atomisation (EHDA). Significant effects of the system’s process parameters on
particle morphology are observed, in particular EHDA voltage. The carrier’s size, shape and surface features
are correlated with its release profile. Importantly, GLS content (something traditionally compromised to
maintain particle integrity) was maximised at 50 wt% whilst maintaining a controlled and spherical shape
and size – making this study novel and extremely important. It is established that GLS-Alginate particles
could offer controlled release over a 2-week administration in pH-neutral conditions; an environment not
yet established as “stable” for alginate, yet reflective of physiological passage. Thus, for the first time
sodium alginate is proven to be a real contender in controlling the delivery of GLS biomolecules.
The reconciliation of these essential stages of drug development highlights some crucial points of focus as
GL continues to undergo rigorous development in the realm of drug discovery.



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