Greater awareness of environmental sustainability has driven many industries to transition from using synthetic organic solvents to greener solvents in their manufacturing. Deep eutectic solvents ...(DESs) have emerged as a highly promising category of green solvents with well-demonstrated and wide-ranging applications, including their use as a solvent in extraction of small-molecule bioactive compounds for food and pharmaceutical applications. The use of DES as an extraction solvent of biological macromolecules, on the other hand, has not been as extensively studied. Thereby, the feasibility of employing DES for biomacromolecule extraction has not been well elucidated. To bridge this gap, this review provides an overview of DES with an emphasis on its unique physicochemical properties that make it an attractive green solvent (e.g., non-toxicity, biodegradability, ease of preparation, renewable, tailorable properties). Recent advances in DES extraction of three classes of biomacromolecules-i.e., proteins, carbohydrates, and lipids-were discussed and future research needs were identified. The importance of DES's properties-particularly its viscosity, polarity, molar ratio of DES components, and water addition-on the DES extraction's performance were discussed. Not unlike the findings from DES extraction of bioactive small molecules, DES extraction of biomacromolecules was concluded to be generally superior to extraction using synthetic organic solvents.
•A blockchain-enabled system is proposed for emissions trading application.•The objective is to improve management and increase abatement investment.•Financial incentive is used to motivate industry ...participants.•Multi-criteria analysis emphasizes the benefit of the system against established ETS.
Emission Trading Scheme (ETS) has dual aims to reduce emission production and stimulate adoption of long-term abatement technology. Whilst it has generally achieved its first aim, its issues are hindering the accomplishment of the second. Several solutions have been proposed to improve ETS’s efficacy, yet none of them have considered the advancement of Industry 4.0. This paper proposes a novel ETS model customised for Industry 4.0 integration. It incorporates blockchain technology to address ETS’s management and fraud issues whilst it utilizes a reputation system in a new approach to improve ETS efficacy. Specific design of how the blockchain technology and reputation system are used to achieve these objectives is showed within this paper. The case study demonstrates the inner working of reputation-based trading system—in which reputation signifies participants performance and commitment toward emission reduction effort. Multi-criteria analysis is used to evaluate the proposed scheme against conventional ETS model. The result shows that the proposed model is a feasible scheme and that the benefits of its implementation will outweigh its drawback.
Microcapsules containing high-density biofilm-like Lactobacillus rhamnosus probiotics, in place of planktonic cells, are developed in order to enhance the cell viability upon exposures to stresses ...commonly encountered during food lifecycle (i.e., heating, freeze-drying, refrigerated storage, and acid). The high-density (HD) capsules are prepared by in situ cultivation of the planktonic cells in the confined space of polysaccharide-based capsules (i.e., chitosan-coated alginate and carrageenan capsules). Compared to their planktonic counterparts, the HD capsules exhibit higher freeze-drying resistance (∼40×) and higher thermotolerance upon prolonged wet heat exposures at 60 and 70 °C (∼12–8000×), but not at higher temperatures even for short exposures (i.e., 80 and 100 °C). The enhanced viability of the HD capsules, however, is not observed during the refrigerated storage and exposure to the simulated gastric juice. The alginate capsules are superior to carrageenan owed to their better cell release profile in the simulated intestinal juice and storage viability.
Oral delivery of curcumin (CUR) has limited effectiveness due to CUR’s poor systemic bioavailability caused by its first-pass metabolism and low solubility. Buccal delivery of CUR nanoparticles can ...address the poor bioavailability issue by virtue of avoidance of first-pass metabolism and solubility enhancement afforded by CUR nanoparticles. Buccal film delivery of drug nanoparticles, nevertheless, has been limited to low drug payload. Herein, we evaluated the feasibilities of three mucoadhesive polysaccharides, i.e., hydroxypropyl methylcellulose (HPMC), starch, and hydroxypropyl starch as buccal films of amorphous CUR–chitosan nanoplex at high CUR payload. Both HPMC and starch films could accommodate high CUR payload without adverse effects on the films’ characteristics. Starch films exhibited far superior CUR release profiles at high CUR payload as the faster disintegration time of starch films lowered the precipitation propensity of the highly supersaturated CUR concentration generated by the nanoplex. Compared to unmodified starch, hydroxypropyl starch films exhibited superior CUR release, with sustained release of nearly 100% of the CUR payload in 4 h. Hydroxypropyl starch films also exhibited good payload uniformity, minimal weight/thickness variations, high folding endurance, and good long-term storage stability. The present results established hydroxypropyl starch as the suitable mucoadhesive polysaccharide for high-payload buccal film applications.
Quercetin (QUE)-a plant-derived flavonoid, is recently established as an effective quorum sensing (QS) inhibiting agent in
-the main bacterial pathogen in bronchiectasis lungs. Successful clinical ...application of QUE, however, is hindered by its low solubility in physiological fluids. Herein we developed a solubility enhancement strategy of QUE in the form of a stable amorphous nanoparticle complex (nanoplex) of QUE and chitosan (CHI), which was prepared by electrostatically driven complexation between ionized QUE molecules and oppositely charged CHI. At its optimal preparation condition, the QUE-CHI nanoplex exhibited a size of roughly 150 nm with a 25% QUE payload and 60% complexation efficiency. The complexation with CHI had no adverse effect on the antibacterial and anticancer activities of QUE, signifying the preservation of QUE's bioactivities in the nanoplex. Compared to the native QUE, the QUE-CHI nanoplex exhibited superior QS inhibition in suppressing the QS-regulated swimming motility and biofilm formation of
, but not in suppressing the virulence factor production. The superior inhibitions of the biofilm formation and swimming motility afforded by the nanoplex were attributed to (1) its higher kinetic solubility (5-times higher) that led to higher QUE exposures, and (2) the synergistic QS inhibition attributed to its CHI fraction.
Lipid–polymer hybrid nanoparticles – polymeric nanoparticles enveloped by lipid layers – have emerged as a potent therapeutic nano-carrier alternative to liposomes and polymeric nanoparticles. Herein ...we perform comparative studies of employing spray drying (SD) and spray freeze drying (SFD) to produce inhalable dry-powder form of drug-loaded lipid–polymer hybrid nanoparticles. Poly(lactic-co-glycolic acid), lecithin, and levofloxacin are employed as the polymer, lipid, and drug models, respectively. The hybrid nanoparticles are transformed into micro-scale nanoparticle aggregates (or nano-aggregates) via SD and SFD, where the effects of (1) different excipients (i.e. mannitol, polyvinyl alcohol (PVA), and leucine), and (2) nanoparticle to excipient ratio on nano-aggregate characteristics (e.g. size, flowability, aqueous reconstitution, aerosolization efficiency) are examined. In both methods, PVA is found more effective than mannitol for aqueous reconstitution, whereas hydrophobic leucineis needed to achieve effective aerosolization as it reduces nano-aggregate agglomeration. Using PVA, both methods are equally capable of producing nano-aggregates having size, density, flowability, yield and reconstitutibility in the range ideal for inhaled delivery. Nevertheless, nano-aggregates produced by SFD are superior to SD in terms of their aerosolization efficiency manifested in the higher emitted dose and fine particle fraction with lower mass median aerodynamic diameter.
Effective encapsulations of drugs that are highly soluble in both water and organic solvents are notoriously difficult to achieve using standard nanoparticle preparation methods, such as ...nanoprecipitation (NPC), single (ESE), and double (DESE) emulsification-solvent-evaporation methods. Modifications of the standard preparation methods are therefore needed to enhance encapsulation efficiency of this group of drugs. The present work investigates the feasibility of enhancing the encapsulation efficiency of highly water and solvent-soluble levofloxacin, which is widely used in antibiotic therapy against pulmonary biofilm infections, into poly(lactic-co-glycolic acid) (i.e. PLGA) nanoparticles. In addition, the nanoparticles are evaluated in terms of their drug loading, size, production yield, and in-vitro drug release profile. Lecithin inclusion into the aqueous phase in the ESE method results in two-fold improvements in the encapsulation efficiency and drug loading (i.e. 23% and 2.3%, w/w, respectively) compared to the standard method. Similar results are obtained when the water-miscibility level of the oil phase is increased in the DESE method. Importantly, these nanoparticles possess size ≈200–300
nm and biphasic extended drug release profiles suitable for anti-biofilm therapy. Lastly, the nanoparticles can be readily transformed into inhalable solid dosage forms without jeopardizing their drug loadings and antibacterial activities.
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Inhaled nano-antibiotics have recently emerged as the promising bronchiectasis treatment attributed to the higher and more localized antibiotic exposure generated compared to native ...antibiotics. Antibiotic nanoparticle complex (or nanoplex in short) prepared by self-assembly complexation with polysaccharides addresses the major drawbacks of existing nano-antibiotics by virtue of its high payload and cost-effective preparation. Herein we developed carrier-free dry powder inhaler (DPI) formulations of ciprofloxacin nanoplex by spray drying (SD) and spray freeze drying (SFD). d-Mannitol and l-leucine were used as the drying adjuvant and aerosol dispersion enhancer, respectively. The DPI formulations were evaluated in vitro in terms of the (1) aerosolization efficiency, (2) aqueous reconstitution, (3) antibiotic release, and (4) antimicrobial activity against respiratory pathogen Pseudomonas aeruginosa. The SFD powders exhibited superior aerosolization efficiency to their SD counterparts in terms of emitted dose (92% versus 66%), fine particle fraction (29% versus 23%), and mass median aerodynamic diameter (3μm versus 6μm). The superior aerosolization efficiency of the SFD powders was attributed to their large and porous morphology and higher l-leucine content. While the SFD powders exhibited poorer aqueous reconstitution that might jeopardize their mucus penetrating ability, their antibiotic release profile and antimicrobial activity were not adversely affected.
The nanoscale formulation of amorphous drugs represents a highly viable supersaturating drug-delivery system for enhancing the bioavailability of poorly soluble drugs. Herein we present a new ...formulation of a nanoscale amorphous drug in the form of a drug–polyelectrolyte nanoparticle complex (or nanoplex), where the nanoplex is held together by the combination of a drug–polyelectrolyte electrostatic interaction and an interdrug hydrophobic interaction. The nanoplex is prepared by a truly simple, green process that involves the ambient mixing of drug and polyelectrolyte (PE) solutions in the presence of salt. Nanoplexes of poorly soluble acidic (i.e., ibuprofen and curcumin) and basic (i.e., ciprofloxacin) drugs are successfully prepared using biocompatible poly(allylamine hydrochloride) and dextran sulfate as the PE, respectively. The roles of salt, drug, and PE in nanoplex formation are examined from ternary phase diagrams of the drug–PE complex, from which the importance of the drug’s charge density and hydrophobicity, as well as the PE ionization at different pH values, is recognized. Under the optimal conditions, the three nanoplexes exhibit high drug loadings of ∼80–85% owing to the high drug complexation efficiency (∼ 90–96%), which is achieved by keeping the feed charge ratio of the drug to PE below unity (i.e., excess PE). The nanoplex sizes are ∼300–500 nm depending on the drug hydrophobicity. The nanoplex powders remain amorphous after 1 month of storage, indicating the high stability owed to the PE’s high glass-transition temperature. FT-IR analysis shows that functional groups of the drug are conserved upon complexation. The nanoplexes are capable of generating prolonged supersaturation upon dissolution with precipitation inhibitors. The supersaturation level depends on the saturation solubility of the native drugs, where the lower the saturation solubility, the higher the supersaturation level. The solubility of curcumin as the least-soluble drug is magnified 9-fold upon its transformation to the nanoplex, and the supersaturated condition is maintained for 5 h.
In lung biofilm infection therapies, the use of lipid-polymer hybrid nanoparticles to encapsulate drugs has emerged as a promising alternative to using liposomes because they have superior ...physicochemical stability and still possess the biofilm affinity and sputum-penetrating ability ofliposomes. To be deemed equally efficacious as liposomes against bacterial biofilms, however, the capability of hybrid nanoparticles to target-release encapsulated drugs at biofilm colonies must be demonstrated. This communication details our investigations into the trigger-release characteristics of hybrid nanoparticles in response to encountering rhamnolipids, which are ubiquitously present in biofilm colonies of Pseudomonas aeruginosa, a major respiratory pathogen. Poly（lactic-co-glycolic acid） and phospbatidylcholine were used as the poly- mer nanoparticle core and lipid coat, respectively. These investigations were performed using compounds from various biopharmaceutical classification systems （BCS） that differ in their lipid-membrane permeabilities. The release of BCS Class II1 compounds, which have poor lipid-membrane permeabilities, was successfully triggered by rhamnolipids at a concentration approximately equal to their clinically observed value, and this release was attributed to the disruption of lipid coats by rhamnolipid micelles. Not unexpectedly, BCS Class I compounds, which have high lipid-membrane permeabilities, were released freely whether or not rhamnolipids were present. The rate of the triggered release can be controlled by incor- porating an additional lipid layer on the hybrid nanoparticles via the electrostatically driven adsorption of lipid vesicles.
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