Synthesis of polymeric nanocapsules by radical UV‐activated interface‐emulsion polymerization

A new methodology is reported that allows a better control of the synthesis of polymeric core–shell nanocapsules. These nanocapsules were made of biocompatible polymers, obtained from poly(ethylene glycol)diacrylate and poly(ethylene glycol) methyl ether methacrylate, and were used as carrier for curcumin as therapeutic agent. The impact of manufacturing factors (time of sonication, time of UV irradiation, and type of monomer) was investigated in relation to the average size of nanocapsules, their distribution, shape, composition, stability, and their capability to deliver curcumin. We successfully synthesized core–shell nanocapsules in various sizes, ranging from 80 nm to 300 nm, by acting either on the process conditions or on the composition of the monomer mixture. This wide range of sizes makes the method here proposed very promising for the production of nanocarriers. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3357–3369     

Enhancement of gemcitabine affinity for biomembranes by conjugation with squalene: differential scanning calorimetry and Langmuir-Blodgett studies using biomembrane models

Molecular interactions between gemcitabine, alone or conjugated with squalene to form the gem-squalene prodrug, with dimyristoylphosphatidylcholine have been investigated by differential scanning calorimetry and Langmuir film balance techniques to gain information about the interaction of gemcitabine and its prodrug with mammalian cell membranes and to evaluate the potential of liposomes as a delivery system for gemcitabine prodrugs. Phospholipids assembled as multilamellar vesicles or monolayers (at the air water interface) have been used as biomembrane models. Different interactions of gemcitabine, its prodrug, and squalene with the lipid were detected by dispersing the compounds in the MLV and were compared with kinetic experiments carried out to consider the ability of the examined compounds to dissolve in an aqueous medium, to migrate through it, and to be captured by multilamellar vesicles. Their ability to be released from drug-loaded liposomes and be taken up by empty vesicles mimicking biomembranes was also considered. Analysis of the differential scanning calorimetry curves reveals that gemcitabine has very little interaction with multilamellar vesicles whereas the gem-squalene prodrug strongly interacts with multilamellar vesicles. The kinetic experiments suggest that an aqueous medium does not permit the prodrug uptake by the biomembrane models, whereas it is allowed when gem-squalene is gradually released by the liposomes. The molecular area/surface pressure isotherms of the gemcitabine/lipid, gem-squalene/lipid, and pure compound monolayers, in agreement with the calorimetric results, indicate that gem-squalene interacts with the phospholipid monolayer with the squalene moiety in contact with the phospholipid chains and gemcitabine protruding in the aqueous medium.     

Regenerable chain-breaking 2,3-dihydrobenzo[b]selenophene-5-ol antioxidants

A series of 2,3-dihydrobenzo[b]selenophene-5-ol antioxidants was prepared by subjecting suitably substituted allyl 4-methoxyphenyl selenides to microwave-induced seleno-Claisen rearrangement/intramolecular Markovnikov hydroselenation followed by boron tribromide-induced O-demethylation. The novel antioxidants were assayed for their capacity to inhibit azo-initiated peroxidation of linoleic acid in a water/chlorobenzene two-phase system containing N-acetylcysteine as a thiol reducing agent in the aqueous phase. Antioxidant efficiency as determined by the inhibited rate of peroxidation, Rinh, increased with increasing methyl substitution (Rinh=46-26 microM/h), but none of the compounds could match alpha-tocopherol (Rinh=22 microM/h). Regenerability as determined by the inhibition time, Tinh, in the presence of the thiol regenerating agent decreased with increasing methyl substitution. Thus, under conditions where the unsubstituted compound 5a inhibited peroxidation for more than 320 min, alpha-tocopherol worked for 90 min and the trimethylated antioxidant 5g for 60 min only. Sampling of the aqueous phase at intervals during peroxidation using antioxidant 5a showed that N-acetylcysteine was continuously oxidized with time to the corresponding disulfide. In the absence of the regenerating agent, compounds 5 inhibited peroxidation for 50-60 min only. A (RO)B3LYP/LANL2DZdp//B3LYP/LANL2DZ model was used for the calculation of homolytic O-H bond dissociation enthalpies (BDE) and adiabatic ionization potentials (IP) of phenolic antioxidants 5. Both BDE (80.6-76.3 kcal/mol) and IP (163.2-156.0 kcal/mol) decrease with increasing methyl substitution. The phenoxyl radical corresponding to phenol 5g gave an intense ESR signal centered at g=2.0099. The H-O bond dissociation enthalpy of the phenol was determined by a radical equilibration method using BHA as an equilibration partner. The observed BDE (77.6+/-0.5 kcal/mol) is in reasonable agreement with calculations (76.3 kcal/mol). As judged by calculated log P values, the lipophilicity of compounds 5 increased slightly when methyl groups were introduced into the phenolic moiety (2.9>C log P<4.2). The capacity of compounds 5a (kinh=3.8x10(5) M-1 s-1) and 5g (kinh=1.5x10(6) M-1 s-1) to inhibit azo-initiated autoxidation of styrene in the homogeneous phase (chlorobenzene) was also studied. More efficient regeneration at the lipid-aqueous interphase is the most likely explanation why the intrinsically poorest antioxidant 5a can outperform its analogues as well as alpha-TOC in the two-phase system. Possible mechanisms of regeneration are discussed and evaluated.     

Synthesis of 1,4-dihydro-2-methyl-4-oxo-nicotinic acid: Ochiai's route failed

The synthesis of 1,4-dihydro-2-methyl- and 1,4-dihydro-1,2-dimethyl-4-oxo-nicotinic acids was accomplished following a route other than Ochiai's procedure, which yielded the isomer 1,6-dihydro-2-methyl-6-oxo-nicotinic acid ethyl ester, and not the 4-oxo-derivative, as reported. Analytical data confirmed the identity of the two isomer oxo-nicotinic acids. UV-vis and potentiometric preliminary data showed that Al(III) does not form complexes with 1,6-dihydro-2-methyl-6-oxo-nicotinic acid ethyl ester in solution, as expected, but with 1,4-dihydro-2-methyl-4-oxo-nicotinic acid.     

Design of Nanotechnological Carriers for Ocular Delivery of Mangiferin: Preformulation Study

(1) Background: Mangiferin (MGN) is a natural compound, showing anti-inflammatory and antioxidant activities for the potential treatment of eye diseases. The poor physicochemical features of MGN (low solubility and high instability) justify its nanoencapsulation into nanostructured lipid carriers (NLC) to improve its ocular bioavailability. (2) Methods: Firstly, MGN-NLC were prepared by the high shear homogenization coupled with the ultrasound (HSH−US) method. Finally, unloaded and MGN-loaded NLC were analyzed in terms of ocular tolerance. (3) Results: MGN-NLC showed good technological parameters suitable for ocular administration (particle size below 200 nm). The ORAC assay was performed to quantify the antioxidant activity of MGN, showing that the antioxidant activity of MGN-NLC (6494 ± 186 μM TE/g) was higher than that of the free compound (3521 ± 271 μM TE/g). This confirmed that the encapsulation of the drug was able to preserve and increase its activity. In ovo studies (HET-CAM) revealed that the formulation can be considered nonirritant. (4) Conclusions: Therefore, NLC systems are a promising approach for the ocular delivery of MGN.     

Optimization of the antioxidant activity of hydroxy-substituted 4-thiaflavanes: a proof-of-concept study

The design and the synthesis of a new family of hydroxy-4-thiaflavanes, in which the reactive phenolic OH is ortho to the sulfur atom of the benzofused oxathiin ring, allowed to prepare antioxidants that show rate constants for the reaction with peroxyl radicals (k(inh)), and bond dissociation energies (BDE), of the ArO-H group identical to those of α-tocopherol, the main component of vitamin E and the most effective lipophilic antioxidant known in nature. The peculiar conformation of the six-membered heterocyclic ring prevents the formation of an intramolecular hydrogen bond between the OH group and the S atom, while ensuring a good stabilization by electron donation of the phenoxyl radical formed after the reaction with peroxyl radicals. The preparation of these compounds was achieved through an inverse electron demand hetero Diels-Alder reaction of styrenes with o-thioquinones, in turn prepared from accurately designed 1,3-dihydroxy arenes. Properly arranging the substitution pattern on the aromatic ring, as in derivatives 9 and 11, allowed to reach values of k(inh) up to 4.0×10(6) M(-1) s(-1) and BDE((OH)) of 77.2 kcal mol(-1). This approach represents an innovative way to obtain highly active antioxidants without using strongly electron donating alkylamino groups which are associated with adverse toxicological profiles.     

Content of micronutrients,mineral and trace elements in some Mediterranean spontaneous edible herbs

Background

The analysis of mineral elements composition was determined in three wild edible herbs (Cichorium intybus L., Sonchus asper L. and Borago officinalis) collected in seven different sampling sites which were characterized by different pollution grade. The detection of mineral elements (Ca, K, Mg and Na), micronutrients (Cu, Fe, Li, Mn and Zn) and heavy metals (As, Cd, Hg, Ni and Pb) was performed.

Results

The results obtained show that in most cases a direct relationship appeared between the amount of elements and the sampling sites. The highest concentrations of heavy metals were found in samples grown in polluted soils. These evaluations showed that contaminants in plants may reflect the environmental state in which they develop.

Conclusion

The examined species are a good source of mineral elements and micronutrients, making them particularly adapt to integrate a well-balanced diet. The accumulation of heavy metals showed that contaminants in plants may reflect the environmental state in which they develop. Results showed high concentrations of heavy metals in samples taken in locations characterized by high human activity and in some samples from the local market, of which no one knows the collection area.