Lutein is a macular pigment that contributes to maintaining eye health. The development of lutein-laden nanocarriers for ocular delivery would have the advantages of user friendliness and cost-effectiveness. Nano-scaled vehicles such as cyclodextrin (CD) and nanoemulsion could overcome the barriers caused by the scleral structure. This study focused on the development of hybrid nanocarriers containing nanoemulsion and CD for scleral lutein accumulation. In the presence of the nanoemulsion, CD forms such as βCD and hydroxyethyl (HE) βCD increased the partition of lutein into the porcine sclera. A combination of nanoemulsion and 2% HEβCD enhanced lutein accumulation to 119±6 µg g⁻¹ h⁻¹, which was 9.2-fold higher than that with lutein suspension alone. We explored the dose effect of CD in nanoemulsion on scleral lutein and found that the scleral accumulation of lutein was enhanced by increasing the CD content. The novel nanoemulsion had 95% drug-loading efficiency and low cytotoxicity in retinal cells. The CD-modified nanoemulsion not only improved the stability and entrapment efficacy of lutein in the aqueous system but also enhanced scleral lutein accumulation. An increase in the partition coefficient of lutein in porcine sclera when using the CD-modified nanoemulsion was also confirmed.

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One of the major obstacles to successful paclitaxel (PTX) chemotherapy is toxic side effects, which are often due to the conventional surfactants used, such as Cremophor EL. PTX is characterized by its hydrophobicity and insolubility, which limit its application in ovarian cancer therapy. The aim of this study was to develop Cremophor EL-free PTX-loaded methoxy poly(ethylene glycol)-block-(lactic-co-glycolic acid) copolymers (PLGA-mPEG) nanoparticles (NPs) using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a novel emulsifier. The ability of nanoparticles loaded with paclitaxel (NP-PTX) to inhibit tumor growth was assessed in vitro and in vivo. The acute toxicity of NP-PTX was also evaluated in vivo. We found that paclitaxel was efficiently encapsulated into PLGA-mPEG NPs with a low concentration of TPGS as the emulsifier. The synthesized NP-PTX demonstrated the desired diameter of 80 nm as characterized by transmission electron microscopy. The NP-PTX also exhibited a sustained release of loaded PTX over 4 d with the same chemotherapeutic efficiency and reduced side effects. NP-PTX-treated cells showed slightly lower cytotoxic responses compared with those treated with free PTX at the same concentration. In vivo studies confirmed that NP-PTX significantly enhanced the median lethal dose of paclitaxel by 10-fold, and a similar effect on the inhibition of tumor growth was achieved in nude mice.

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Amino-linked benzoxazolyl/benzothiazolyl/benzimidazolyl quinazolines were prepared and their antimicrobial activity studied. The nitro-substituted benzothiazolyl quinazoline (8f) may be a potential antibacterial agent against Staphylococcus aureus and nitro-substituted benzimidazolyl quinazoline (9f) may be a potential antifungal agent against Aspergillus niger.

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In this study, we applied an electrospinning (ES) method, which is mainly employed in the textile industry, to the field of pharmaceuticals. We developed and modified an ES instrument and then utilized it to produce methacrylic acid copolymer S (MAC) nano-fibers to prepare tablets. By attaching a conductor rod made from stainless steel to the central part of the nano-fiber-collection plate of the ES apparatus, a MAC nano-fiber sheet could be produced effectively. In addition, we studied various operating conditions for this new ES method, including needle gauge, voltage between the electrodes, distance between the needle and nano-fiber-collection plate and the flow rate of MAC polymer solution, but these had no significant effect on the diameter of MAC nano-fibers. On the other hand, the viscosity (concentration) of MAC polymer solution and permittivity of solvent used to dilute MAC were closely related to the mean diameter of the nano-fibers. Tableting of MAC nano-fibers was performed using a tableting machine without lubricants, and addition of Tween 20 to the tablets enabled regulation of the release profile of a water-soluble drug. The modified ES method reported here is a useful technique for the controlled-release of drugs and has wide-ranging potential for pharmaceutical applications.

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The purpose of this study was to characterize the non-aqueous nanosuspension of a hydrophilic drug prepared by bead milling for cutaneous application. Riboflavin was used as the model hydrophilic drug. The non-aqueous nanosuspensions were prepared by grinding riboflavin with zirconia beads using eight non-aqueous bases. The mean particle size of riboflavin in the suspensions ranged from 206 to 469 nm, as determined by the dynamic light scattering method. Among the well-dispersed samples, riboflavin nanosuspension prepared in oleic acid was selected for evaluation of the drug permeability through rat skin. The cumulative amount and permeation rate of riboflavin from the nanosuspension were approximately three times higher than those for unprocessed riboflavin in oleic acid. Fluorescence imaging of the riboflavin nanosuspension suggested improved penetration of riboflavin into the stratum corneum. Furthermore, the addition of polysorbate 65 or polyglyceryl-6 polyricinoleate to the nanosuspension prepared in oleic acid markedly improved the riboflavin dispersibility. These results show that the preparation of a nanosuspension in a non-aqueous base by bead milling is one of the simple methods to improve the skin permeability of hydrophilic drugs.

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The manufacture of highly drug-loaded fine globular granules eventually applied for orally disintegrating tablets has been investigated using a unique multi-functional rotor processor with acetaminophen, which was used as a model drug substance. Experimental design and statistical analysis were used to evaluate potential relationships between three key operating parameters (i.e., the binder flow rate, atomization pressure and rotating speed) and a series of associated micromeritics (i.e., granule mean size, proportion of fine particles (106–212 µm), flowability, roundness and water content). The results of multiple linear regression analysis revealed several trends, including (1) the binder flow rate and atomization pressure had significant positive and negative effects on the granule mean size value, Carr’s flowability index, granular roundness and water content, respectively; (2) the proportion of fine particles was positively affected by the product of interaction between the binder flow rate and atomization pressure; and (3) the granular roundness was negatively and positively affected by the product of interactions between the binder flow rate and the atomization pressure, and the binder flow rate and rotating speed, respectively. The results of this study led to the identification of optimal operating conditions for the preparation of granules, and could therefore be used to provide important information for the development of processes for the manufacture of highly drug-loaded fine globular granules.

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A novel series of quinzoline based compounds (IIIa–d, VIa–f, IXa–f) were designed, synthesized and screened for their inhibitory activity towards the PDE4B isoform. The in vivo anti-inflammatory effect of the titled compounds (IIIa–d, VIa–f, IXa–f) as well as their effect on the level of tumor necrosis factor (TNF-α) were evaluated. Among all of the synthesized compounds, IXb, IXd and IXf, exhibited good inhibitory activity against PDE4B enzyme with inhibition percentages of 42, 62 and 68%, respectively. Most of the tested compounds showed potent anti-inflammatory activity compared to indomethacin with a marked decrease in TNF-α level. The ulcerogenic effect of the tested compounds was also examined. The gastric mucosa of the tested animals remained intact after oral administration of the hit compounds. Additionally, docking study was used to explore the possible binding mode of the active compounds on the PDE4B enzyme as well as to illustrate the selectivity of the active hits on the PDE4B isoform.

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Newly identified cyclic sulfoxides—garlicnins K₁ (1), K₂ (2), and H₁ (3)—were isolated from the acetone extracts of the bulbs of garlic, Allium sativum. Garlicnin H₁ (3) demonstrated potential to suppress tumor cell proliferation by regulating macrophage activation. The structures of garlicnins K₁ and K₂, 3,4-dimethyl-5-allyl-tetrahydrothiophen-2-one-S-oxides, and the structure of garlicnin H₁, 3-carboxy-3-hydroxy-4-methyl-5-allylsulfoxide-tetrahydrothiophen-2-(ethane-1,2-diol)-S-oxide were characterized by spectroscopic analysis.

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An attempt to synthesize aglycone 1 derived from 2,3,5,4′-tetrahydroxystilbene-2-O-β-glucoside (THSG) via the Wittig reaction and Mizoroki–Heck reaction is described. In the Wittig protocol, 2,3,5,4′-tetramethoxystilbene 2 was obtained. Additionally, a palladium-catalyzed Mizoroki–Heck reaction strategy yielded 2-aryl-2,3-dihydrobenzofuran 13 instead of derivative 12 in good yield.

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When a solution of 5-aminolevulinic acid (ALA) was incubated with acetaldehyde at neutral pH, a product was generated. This product was identified as 3-ethylpyrazine-2,5-dipropanoic acid (ETPY). ETPY was stable at neutral pH. It has been reported that ALA dimerizes at neutral pH generating 3,6-dihydropyrazine-2,5-dipropanoic acid (DHPY), and subsequently resulting in pyrazine-2,5-dipropanoic acid (PY) by autoxidation. In the present reaction, DHPY generated from ALA reacted with acetaldehyde, resulting in ETPY. Preadministration of ALA 3 min prior to acetaldehyde injection supressed the toxicity of acetaldehyde in male mice. These results suggest that ALA may be useful as a scavenger for acetaldehyde.

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The reaction of triarylantimony diacetates [Ar₃Sb(OAc)₂] with dialkyl H-phosphites [H-PO(OR)₂] in the presence of a Pd(PPh₃)₄ (5 mol%) catalyst led to the formation of arylphosphonates in moderate to excellent yield under base-free conditions. This reaction is the first example of carbon–phosphorus bond formation by using an organoantimony compound as a pseudo-halide.

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A number of new 2,6-disubstituted-1-deazanebularine analogues as well as two structurally related pyrazole-fused tricyclic nucleosides were prepared. Their synthesis was carried out by the conversion of 6-amino-2-picoline to a suitable 1-deazapurine, followed by a Vorbrüggen type glycosylation and subsequent elaboration of the condensed pyrazole ring. The synthesized nebularine analogues proved to be weak adenosine deaminase inhibitors.

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An improved and efficient method for the preparation of torezolid based on Suzuki cross-coupling reaction as the key step was developed on a gram scale in five steps. The total yield was 44% and the optical purity of torezolid by the improved method was above 99%.

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