Ching-Yee Loo

Biosynthesis of polyhydroxyalkanoate copolymers from mixtures of plant oils and 3-hydroxyvalerate precursors

The combination of plant oils and 3-hydroxyvalerate (3HV) precursors were evaluated for the biosynthesis of polyhydroxyalkanoate (PHA) copolymers containing 3HV monomers by Cupriavidus necator H16. Among various mixtures of plant oils and 3HV-precursors, the mixture of palm kernel oil and sodium propionate was suitable for the biosynthesis of high concentration of PHA (6.8gL(-1)) containing 7mol% of 3HV. The 3HV monomer composition can be regulated in the range of 0-23mol% by changing culture parameters such as the initial pH, and the nitrogen source and its concentration. PHA copolymers with high weight-average molecular weights (Mw) ranging from 1,400,000 to 3,100,000Da were successfully produced from mixtures of plant oils and 3HV-precursors. The mixture of plant oils and sodium propionate resulted in PHA copolymers with higher M(w) compared to the mixture of plant oils and sodium valerate. DSC analysis on the PHA containing 3HV monomers showed the presence of two distinct melting temperature (Tm), which indicated that the PHA synthesized might be a blend of P(3HB) and P(3HB-co-3HV). Sodium propionate appears to be the better precursor of 3HV than sodium valerate.

Curcumin and its Derivatives: Their Application in Neuropharmacology and Neuroscience in the 21st Century

Curcumin (diferuloylmethane), a polyphenol extracted from the plant Curcuma longa, is widely used in Southeast Asia, China and India in food preparation and for medicinal purposes. Since the second half of the last century, this traditional medicine has attracted the attention of scientists from multiple disciplines to elucidate its pharmacological properties. Of significant interest is curcumin’s role to treat neurodegenerative diseases including Alzheimer’s disease (AD), and Parkinson’s disease (PD) and malignancy. These diseases all share an inflammatory basis, involving increased cellular reactive oxygen species (ROS) accumulation and oxidative damage to lipids, nucleic acids and proteins. The therapeutic benefits of curcumin for these neurodegenerative diseases appear multifactorial via regulation of transcription factors, cytokines and enzymes associated with (Nuclear factor kappa beta) NFκB activity. This review describes the historical use of curcumin in medicine, its chemistry, stability and biological activities, including curcumins anti-cancer, anti-microbial, anti-oxidant, and anti-inflammatory properties. The review further discusses the pharmacology of curcumin and provides new perspectives on its therapeutic potential and limitations. Especially, the review focuses in detail on the effectiveness of curcumin and its mechanism of actions in treating neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases and brain malignancies.

Recent advances in curcumin nanoformulation for cancer therapy

Introduction: Natural compounds are emerging as effective agents for the treatment of malignant diseases. Curcumin (diferuloylmethane), the active constituent of turmeric extract, has gained significant interest as a plant-based compound with anti-cancer properties. Curcumin is physiologically very well tolerated, with negligible systemic toxicity observed even after high oral doses administration. Despite curcumin’s superior properties as an anti-cancer agent its applications are limited due to its low solubility and physico-chemical stability, rapid systemic clearance and low cellular uptake. Areas covered: This review focuses on the development of curcumin nano-particle formulation to improve its therapeutic index through enhanced cellular uptake, localization to targeted areas and improved bioavailability. The feasibility of nano-formulation in delivering curcumin and the limitations and challenges in designing and administrating the nano-sized curcumin particles are also covered in this review. Expert opinion: Nanotechnology is a promising tool to enhance efficacy and delivery of drugs. In this context, formulation of curcumin as nano-sized particles could reduce the required therapeutic dosages and subsequently reduced its cell toxicity. These nanoparticles are capable to provide local delivery of curcumin targeted to specific areas and thereby preventing systemic clearance. In addition, using specific coating, better pharmacokinetic and internalization of nano-curcumin could be achieved. However, the potential toxicity of nano-carriers for curcumin delivery is an important issue, which should be taken into account in curcumin nano-formulation.

Superhydrophobic, nanotextured polyvinyl chloride films for delaying Pseudomonas aeruginosa attachment to intubation tubes and medical plastics

Bacterial attachment onto the surface of polymers in medical devices such as polyvinyl chloride (PVC) is influenced by the physicochemical properties of the polymer, including its surface hydrophobicity and roughness. In this study, to prevent biofilm formation onto PVC devices, the PVC surface was modified using a combination of solvent (tetrahydrofuran) and non-solvents (i.e. ethanol and methanol). The surface of unmodified PVC was smooth and relatively hydrophobic (water contact angle (CA)=80°). Ethanol-treated PVCs revealed the presence of micron-sized particulates and porous structures as the concentration of ethanol was increased. Surface hydrophobicity (measured in terms of CA) increased from 73° to 150° as the ethanol concentration increased from 15% to 35% (v/v). In general, methanol-treated PVCs were more hydrophilic compared to those treated with ethanol. The colonization of Pseudomonas aeruginosa PAO1 onto unmodified PVC surface was rapid, and individual bacterial cells could be seen after 6h incubation. On the surface of treated PVC, the secretion of extracellular matrix layers was evident at 18 h and P. aeruginosa PAO1 start to form microcolonies at 24h of incubation. The initial attachment of P. aeruginosa PAO1 was delayed to 18 and 24h, respectively in the PVCs treated with 25% (v/v) and 35% (v/v) ethanol. It can be concluded that the treatment used in this study to prepare superhydrophobic PVC surface prevented the colonization of bacteria up to 24h after culture.

A review of chemical surface modification of bioceramics: effects on protein adsorption and cellular response.

Calcium phosphates (CaPs) are ideal biomaterials for bone repair because of the similarities between their chemical structure and the mineral phase of hard biological tissues (e.g., bones and teeth). Since CaP bone grafts exhibit superior biocompatibility and strong osseointegration properties, they have been widely investigated for use as an in situ carrier for delivery of anti-resorptive and osteogenic drugs. The surface properties of CaP govern the affinity and the binding mechanisms between biological macromolecules (e.g., proteins) and the CaP surface, which indirectly determines the interactions between bone cells and implanted CaP biomaterials. These surface properties ultimately play a pivotal role in determining the success of CaP as bone implants and/or drug carriers. This review provides an in-depth discussion of the current methodologies used to regulate the surface chemistry of CaP and their subsequent effects in regards to protein adsorption and delivery, as well as cell/materials interactions.

Modulating protein adsorption onto hydroxyapatite particles using different amino acid treatments

Hydroxyapatite (HA) is a material of choice for bone grafts owing to its chemical and structural similarities to the mineral phase of hard tissues. The combination of osteogenic proteins with HA materials that carry and deliver the proteins to the bone-defective areas will accelerate bone regeneration. The study investigated the treatment of HA particles with different amino acids such as serine (Ser), asparagine (Asn), aspartic acid (Asp) and arginine (Arg) to enhance the adsorption ability of HA carrier for delivering therapeutic proteins to the body. The crystallinity of HA reduced when amino acids were added during HA preparation. Depending on the types of amino acid, the specific surface area of the amino acid-functionalized HA particles varied from 105 to 149 m2 g–1. Bovine serum albumin (BSA) and lysozyme were used as model proteins for adsorption study. The protein adsorption onto the surface of amino acid-functionalized HA depended on the polarities of HA particles, whereby, compared with lysozyme, BSA demonstrated higher affinity towards positively charged Arg-HA. Alternatively, the binding affinity of lysozyme onto the negatively charged Asp-HA was higher when compared with BSA. The BSA and lysozyme adsorptions onto the amino acid-functionalized HA fitted better into the Freundlich than Langmuir model. The amino acid-functionalized HA particles that had higher protein adsorption demonstrated a lower protein-release rate.

Combination of Silver Nanoparticles and Curcumin Nanoparticles for Enhanced Anti-biofilm Activities

Biofilm tolerance has become a serious clinical concern in the treatment of nosocomial pneumonia owing to the resistance to various antibiotics. There is an urgent need to develop alternative antimicrobial agents or combination drug therapies that are effective via different mechanisms. Silver nanoparticles (AgNPs) have been developed as an anti-biofilm agent for the treatment of infections associated with the use of mechanical ventilations, such as endotracheal intubation. Meanwhile curcumin, a phenolic plant extract, has displayed natural anti-biofilm properties through the inhibition of bacterial quorum sensing systems. The aim of this study was to investigate the possible synergistic/additive interactions of AgNPs and curcumin nanoparticles (Cur-NPs) against both Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) microorganisms. The combination of AgNPs and Cur-NPs (termed Cur-SNPs) at 100 μg/mL disrupted 50% of established bacterial biofilms (formed on microtiter plates). However, further increase in the concentration of Cur-SNPs failed to effectively eliminate the biofilms. To achieve the same effect, at least 500 μg/mL Cur-NP alone was needed. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) revealed that combination therapy (Cur-SNPs) was the most potent to eradicate preformed biofilm compared to monodrug therapy. These agents are also nontoxic to healthy human bronchial epithelial cells (BEAS2B).

Nano- and micro-based inhaled drug delivery systems for targeting alveolar macrophages

Introduction: Macrophages are the most versatile cells in the hematopoietic system and are strategically distributed in tissues to fight pathogens or other foreign particles. In the lung, however, for intracellular infections such as tuberculosis, pneumonia and aspergillosis, bacteria and fungi utilize the alveolar macrophage as a breeding ground. This has become a challenge for the treatment of these infections, as most drugs do not effectively reach the macrophages at therapeutic levels. Alveolar macrophages also play an important role to initiative adaptive immunity toward combating inflammation and cancer in the lung. Areas covered: This review focuses on the development of micro- and nanotechnology-based drug delivery systems to target alveolar macrophages in association with intracellular infections, cancer and lung inflammation. Aspects of nanoparticle and micron-sized particle engineering through exploitation of particles’ physicochemical characteristics such as particle size, surface charge and geometry of particles are discussed. In addition, the application of nanocarriers such as liposomes, polymeric nanoparticles and dendrimers are covered with respect to macrophage targeting. Expert opinion: Drug delivery targeted to alveolar macrophages in the lung is becoming a reality thanks to micro- and nanotechnology breakthrough. The literature review shows that regulation of physicochemical parameters of particles could be a recipe to enhance macrophage targeting and uptake. However, there is still a need to identify more target-specific receptors in order to facilitate drug targeting. Besides that, the toxicity of nanocarriers arising from prolonged residence in the lung should be taken into consideration during formulation.

Synthesis and characterization of hydroxyapatite with different crystallinity: Effects on protein adsorption and release†

Increasing demand exists for the development of a tissue-engineered alternative in the repair of nonunion and critical-sized bone defects. The delivery of osteoinductive proteins, such as bone morphogenetic proteins (BMPs), to replicate physiological bone-healing process appears a logical and promising option, but is currently limited in its clinical application due to lack of a suitable drug carrier. The study aimed to investigate the effects of the crystallinity of hydroxyapatite (HA) drug carrier on adsorption of proteins onto and their release from the carrier. HA samples with different crystallinities were synthesized under controlled conditions, that is, pH, temperature, and maturation time, and characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and surface area analyzer. Results demonstrated that both bovine serum albumin (BSA) and cytochrome C had a greater tendency to bind onto amorphous calcium phosphate (ACP) than crystalline HA, and the adsorption rate was correlated oppositely with the HA crystallinity. For both BSA and cytochrome C, the release kinetics of protein from HA depended on the crystallinity of HA, in which ACP had the highest release rate at 74%, whereas only 15% of proteins were released from the highly crystalline HA over a 14-day period. Burst release within 12 h of incubation was observed for all groups.

Non-cytotoxic silver nanoparticle-polyvinyl alcohol hydrogels with anti-biofilm activity: designed as coatings for endotracheal tube materials.

Endotracheal intubation is commonly associated with hospital-acquired infections as the intubation device acts as reservoir for bacterial colonization in the lungs. To reduce the incidence of bacterial colonization on the tubes, hydrogel coatings loaded with antimicrobial agents are gaining popularity. The aim of this study was to incorporate silver nanoparticles (AgNPs) into polyvinyl alcohol (PVA) to form stable hydrogels. Embedding AgNPs into PVA resulted in a decreased elongation at break and an increased tensile strength compared to PVA alone. The Ag release profile varied as a function of the degree of hydrolysis of PVA: the higher degree of hydrolysis demonstrated a lower release rate. Fourier infrared transform spectroscopy demonstrated that AgNPs interacted exclusively with the –OH groups of PVA. AgNP-loaded PVA was non-toxic against human normal bronchial epithelial cells while effective against the attachment of Pseudomonas aeruginosa and Staphylococcus aureus with a greater effect on P. aeruginosa.