Incommensurate Lamellar Phase from Long Chain Mannosides : Investigation by X-Ray Scattering and Replica Exchange Molecular Dynamics (REMD)

Acknowledgement This work was supported by the Ministry of Education of Malaysia [600-IRMI/FRGS 5/3 (357/2019)]. We are thankful for the computational facility provided by the National Center for High-Performance Computing of Taiwan used to perform calculations reported in this work. AMF would like to acknowledge the Scottish Government and the Royal Society of Edinburgh, for the award of one SAPHIRE project.Peer reviewedPostprin

Recent advances in the development of multifunctional lipid-based nanoparticles for co-delivery, combination treatment strategies, and theranostics in breast and lung cancer

Cancer nanomedicines and the development of state-of-the-art multifunctional lipid-based nanoparticles (NPs) has become a fundamental resource in resolving challenging biomedical questions and physiological impediments. Since the approval of the first cancer nanomedicine by the U.S. Food and Drug Administration (FDA) in 1995, advances in smart nanomedicines have been made towards the functionalisation of NP surfaces and interiors for enhanced therapeutic effects and intratumoural distribution, and avoidance of rapid clearance and degradation occurring in vivo. The strategies include advances seen in the engineering of both lipid-based and hybrid lipid (e.g., a combination of lipidic and polymeric components) NPs for co-delivery, tumour targeting, combination therapy, and cancer theranostics. The development of multifunctional nanoplatforms is, therefore, a key concept in the amelioration of progressive and/or drug-resistant cancer cells and bypass of barriers in the delivery of anticancer molecules. Herein, we consolidate information on the recent advances in multifunctional lipid-based NPs for application in therapeutic and/or theranostic intervention of breast and lung cancer in animal models and human clinical trials. Respectively, both cancer types are among the leading cases of newly diagnosed cancer worldwide and are major contributors to cancer-related deaths in men and women. A quick overview on the challenges and promising ideas for developing safe-by-design multifunctional lipid-based cancer nanomedicines are also presented

Self-Assembly, Thermotropic, and Lyotropic Phase Behavior of Guerbet Branched-Chain Maltosides

Five synthetic β-d-maltosides derived from Guerbet branched alcohols, whose total hydrocarbon chain length ranged from C₈ to C₂₄, were synthesized to a high anomeric purity, and their thermal properties, liquid-crystalline phases, and structures were characterized using differential scanning calorimetry, optical polarizing microscopy, and small-angle X-ray scattering. Thermal investigations of all anhydrous Guerbet maltosides showed that they do not form solid crystals but undergo a glass transition upon temperature change in the range of 35–53 °C. The glassy crystalline structure turns into the liquid-crystalline structure upon heating or addition of water. In thermotropic studies, the lamellar phase formation is prominent in shorter-chain-length analogues, whereas the longer-chain compounds exhibit a more frustrated form of self-assembly in the formation of a metastable state, polymorphism, and inverse bicontinuous cubic structure (<i>Ia</i>3<i>d</i>). The excess water conditions show that the phase formation is dominated by the lamellar phase for the longer-chain compounds. Normal micellar solution was observed in the shortest-chain-length maltosides because of the enlargement of hydrated maltose headgroups. The self-assembly of both dry and fully hydrated Guerbet maltosides, which exhibited glass-forming abilities and showed surface activity and also the ability to act as membrane-stabilizing compounds, makes them ideal candidates for practical use in industry as well as biomedical research

New Insight into the Origin of the Red/Near-Infrared Intense Fluorescence of a Crystalline 2‑Hydroxychalcone Derivative: A Comprehensive Picture from the Excited-State Femtosecond Dynamics

Fluorescence upconversion and transient absorption techniques are used to explain the source of the intense red/near-infrared emission of crystalline 4-dimethylamino-2′-hydroxychalcone. We found that the initially excited enol form undergoes tautomerization in 3 ps to form the keto tautomer. The latter is stable in the ground state as a consequence of J-type aggregation in the crystal packing and is manifested in an absorption peak at 550 nm that spectrally overlaps with the short-lived enol emission, leading to self-reabsorption and adding a factor to the complete depletion of the enol emission. Relaxation of the keto tautomer takes place in the form of intense fluorescence (600–750 nm) with 1.7 ns lifetime. The different spectroscopy in solution is due to vibrational cooling (300 fs), followed by solvation dynamics (5 ps in methanol) and twisting of the hydroxyphenyl ring (16 ps), before relaxation of the enol tautomer in the form of weak green fluorescence with 350 ps lifetime

Swelling of Bicontinuous Cubic Phases in Guerbet Glycolipid: Effects of Additives

Inverse bicontinuous cubic phases of lyotropic liquid crystal self-assembly have received much attention in biomedical, biosensing, and nanotechnology applications. An <i>Ia</i>3<i>d</i> bicontinuous cubic based on the gyroid G-surface can be formed by the Guerbet synthetic glucolipid 2-hexyl-decyl-β-d-glucopyranoside (β-Glc–OC₆C₁₀) in excess water. The small water channel diameter of this cubic phase could provide nanoscale constraints in encapsulation of large molecules and crystallization of membrane proteins, hence stresses the importance of water channel tuning ability. This work investigates the swelling behavior of lyotropic self-assembly of β-Glc–OC₆C₁₀ which could be controlled and modulated by different surfactants as a hydration-modulating agent. Our results demonstrate that addition of nonionic glycolipid octyl-β-d-glucopyranoside (β-Glc–OC₈) at 20 and 25 mol % gives the largest attainable cubic water channel diameter of ca. 62 Å, and formation of coacervates which may be attributed to a sponge phase were seen at 20 mol % octyl-β-d-maltopyranoside (β-Mal–OC₈). Swelling of the cubic water channel can also be attained in charged surfactant-doped systems dioctyl sodium sulfosuccinate (AOT) and hexadecyltrimethylammonium bromide (CTAB), of which phase transition occurred from cubic to a lamellar phase. Destabilization of the cubic phase to an inverse hexagonal phase was observed when a high amount of charged lecithin (LEC) and stearylamine (SA) was added to the lipid self-assembly

Non-lamellar lyotropic liquid crystalline nanoparticles as nanocarriers for enhanced drug encapsulation of atorvastatin calcium and proanthocyanidins

Atorvastatin calcium (ATV) and proanthocyanidins (PAC) have a strong antioxidant activity, that can benefit to reduce the atherosclerotic plaque progression. Unfortunately, the bioavailability of ATV is greatly reduced due to its limited drug solubility while the PAC drug is unstable upon exposure to the atmospheric oxygen. Herein, the lyotropic liquid crystalline nanoparticles (LLCNPs) constructed by a binary mixture of soy phosphatidylcholine (SPC) and citric acid ester of monoglyceride (citrem) at different weight ratios were used to encapsulate the hydrophobic ATV and hydrophilic PAC. The LLCNPs were further characterized by small-angle X-ray scattering and dynamic light scattering. Depending on the lipid composition, the systems have a size range of 140–190 nm and were able to encapsulate both drugs in the range of 90–100. Upon increasing the citrem content of drug-loaded LLCNPs, the hexosomes (H2) was completely transformed to an emulsified inverse micellar (L2). The optimum encapsulation efficiency (EE) of ATV and PAC were obtained in citrem/SPC weight ratio 4:1 (L2) and 1:1 (H2), respectively. There was a substantial change in the mean size and PDI of the nanoparticles upon 30 days of storage with the ATV-loaded LLCNPs exhibiting greater colloidal instability than PAC-loaded LLCNPs. The biphasic released pattern (burst released at the initial stage followed by the sustained released at the later stage) was perceived in ATV formulation, while the burst drug released pattern was observed in PAC formulations that could be attributed by its internal H2 structure. Interestingly, the cytokine studies showed that the PAC-LLCNPs promisingly up regulate the expressions of tumor necrosis factor-alpha (TNF-α) better than the drug-free and ATV-loaded LLCNPs samples. The structural tunability of citrem/SPC nanoparticles and their effect on physicochemical characteristic, biological activities and potential as an alternative drug delivery platform in the treatment of atherosclerosis are discussed