Topic I – Can Lycopene Chylomicron be developed as a botanic drug?

Subtopic 1: Tomato extract provide lycopene with improved bioavailability

Lycopene has been demonstrated to be effective against diseases such as skin cancer, prostate cancer and cardiovascular disease. However, questions over its clinical use remain as it has an extremely low bioavailability. To combat this, Prof. Chen has prepared stable lycopene chylomicron and lycopene micelle by a microemulsion technique with average particle size being 131.5 nm and 7.5 nm, respectively.

Subtopic 2: Shape-dependent bioavailability

Lycopene chylomicron showed a higher oral bioavailability than lycopene micelle as the former provided better protection for the lycopene due to a thick layer visualized under the transmission electron microscope. Also, the bioavailability can be raised by 10-fold for lycopene chylomicron compared to previously published reports. Consequently, both size and shape should be taken into account for oral bioavailability evaluation. Lycopene micelle may be useful for intravenous injection.

Subtopic 3: Lycopene chylomicron can be used for treatment of patients with prostatauxe syndrome

A phase III clinical trial conducted in Taiwan and USA has completed in 2017 and demonstrated that lycopene chylomicron was effective in the treatment of patients with prostatauxe syndrome. Lycopene chylomicron can be expected to be the first botanic drug in the world for treatment of patients with prostatauxe syndrome.

TOPIC II – Can Tea Leaf Waste Nanoemulsion be used for cancer treatment?

Subtopic 1: Nanoemulsion prepared from tea leaf waste and its characteristics

Oolong tea, a semi-fermented tea widely consumed in Asian countries, such as Taiwan and China, has been shown to contain an abundant amount of catechins. The catechins have been demonstrated to be protective against many types of chronic diseases such as inflammation, atherosclerosis and cancer. However, their high instability and poor bioavailability have limited their potential for further in vivo application. To overcome this issue, Prof. Chen successfully prepared a highly stable catechin nanoemulsion with a particle size of 11.3 nm, zeta potential of -67.2 mV and encapsulation efficiency of 83.4% by mixing catechin extract from oolong tea leaf waste with lecithin, Tween 80 and water in an appropriate proportion.

Subtopic 2: Nanoemulsion can inhibit PC-3 and DU-145 prostate cancer cell growth

Catechin nanomeulsions were more effective than catechin extracts in inhibiting growth of prostate cancer cells DU-145 with the IC₅₀ being 13.52 μg/mL and 214.6 μg/mL after 48 h incubation, respectively. Both catechin extracts and nanoemulsions as well as the anti-cancer drug paclitaxel could up-regulate p53 expression and down-regulate cyclin A, CDK2, cyclin B and CDK1 expressions through p27-dependent pathway. Also, the activities of caspase-8, caspase-9 and caspase-3 were raised through inhibition of bcl-2 expression and elevation of bax expression, leading to a rise of cytochrome C release from mitochondria.

Subtopic 3: Nanoemulsion can inhibit prostate tumor growth in an animal model

Both treatments of catechin nanoemulsion at 20 μg/mL and paclitaxel at 10 μg/mL were the most effective in inhibiting tumor volume and weight in mice through a decrease of both EGF and VEGF levels in serum, suggesting that catechin nanoemulsion prepared from Oolong tea leaf waste may be used for treatment of prostate cancer instead of paclitaxel in the future.

TOPIC III – Can Poly(g-glutamic acid) be used as a detoxifying agent in vivo?

Subtopic 1: PGA-based magnetic nanoparticles – preparation and characteristics

Owing to an increase in antibiotic-resistant microorganisms and side effects associated with conventional detoxification chelation therapy, Prof. Chen explored the potential of an edible and biodegradable biopolymer poly(g-glutamic acid) (PGA) as an for alternative antimicrobial and detoxifying agent. The PGA based magnetic nanoparticles (PGA-MNPs) were synthesized by coprecipitation of ferric chloride and ferrous sulfate using ammonium hydroxide, followed by without coating (bare MNPs) and 8% coating with sodium salt of PGA or 11.8% with calcium salt of g-PGA. Characterization of PGA-MNPs showed their morphology to be spherical in shape with the particle size of bare-MNPs, NaPGA-MNPs and CaPGA-MNPs being 8.5, 11.8 and 14 nm, and magnetic property being 70.3, 61.7 and 56.6 emu/g, respectively.

Subtopic 2: Antimicrobial effects of PGA-MNPs

Evaluation of both NaPGA- and CaPGA-MNPs for their antimicrobial activity by agar dilution assay showed a lower minimum inhibitory concentration in Salmonella enteritidis SE 01 than the commercial antibiotics linezolid and cefaclor, but the former was effective against Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 10832, whereas the latter was effective against Escherichia coli O157:H7 TWC 01.

Subtopic 3: In vitro removal of heavy metals by PGA and PGA-MNPs

A rapid adsorption of heavy metals lead and cadmium at pH 5-8 was observed with a Langmuir adsorption capacity (LAC) of 98.70 and 31.13 mg/g in deionized water and 147.71 and 23.15 mg/g in simulated gastrointestinal fluid, respectively. Interestingly, the lead adsorption capacity remained unaffected in the presence of several essential metals such as Cu, Fe, Zn, Mg, Ca and K, implying that the mineral content under physiological condition may not affect lead adsorption during in vivo application. Heavy metal removal by only PGA also showed similar results with LAC of 213.58 and 41.85 mg/g for lead and cadmium at pH 5.5, respectively.

Subtopic 4: In vivo removal of heavy metals by PGA

In in vivo study, the lead-induced intoxication of mice with PGA was evaluated by comparing with a standard drug meso-2,3-dimercaptosuccinic acid. Administration of 200 and 400 mg/kg of PGA reduced the accumulation of lead in liver, heart and testis, with the latter dose being effective in decreasing the lead content in kidney and spleen. Also, the PGA at both doses reduced TBARs in kidney and brain, elevated d-aminolevulinic acid dehydrase activity in blood and decreased the activities of both pyruvic transaminase and lactic dehydrogenase in serum.