Solubility Of Conjugates Research Articles

Enhanced bioaccesibility of selective PDE4 inhibitor N-(3,4-dihydro-2h-1,5-benzodioxepin-7-yl) pyridine-4-carboxamide using polyamidoamine dendrimer

The aim of this study was to improve the aqueous solubility of highly hydrophobic but selective PDE4 inhibitor N-(3,4-dihydro-2h-1,5-benzodioxepin-7-yl) pyridine-4-carboxamide by associating it with polyamidoamine dendrimer. The PAMAM dendrimer restraining ethylenediamine core synthesized by a divergent approach was utilized for encapsulation. The solubility of conjugates was evaluated on the basis of concentration and generation of the dendrimer, pH of the solution, and temperature. The phase solubility diagram confirmed an increase in aqueous solubility of drug with increase in dendrimer concentration with respect to pH in the order 9.0 > 7.0 > 4.0. Moreover, values of thermodynamic parameters such as negative value of ΔHo, positive value of ΔSo and ΔGo reflects an exothermic complexation, presence of number of particles and spontaneity of the complexation. Overall, investigations validate the enhancement in solubility of drug after complexation with polyamidoamine dendrimer which further confirmed promising bioactivity of the drug-dendrimer conjugates.

Synthesis, solubility and antitumor activity of maslinic acid derivatives

Maslinic acid (MA), a pentacyclic triterpenoid obtained from olives that is characterized by its antiproliferative activity in tumor cells, has become a promising molecule that could be modified to improve cancer treatment. In this work we have synthesized in good yields several new MA conjugates, including glycerin, oligo(ethylene glycol), and amino acid derivatives (compounds 3a-f). The synthesis offers the possibility of recovering unreacted MA, and thus the scaling up of the process. For the tyramine-MA conjugate, compound 3f or TMA, the preparation has been optimized to a one-pot reaction. Solubility of conjugates in polar solvents has been measured, showing a marked increase of solubility with respect to MA. Moreover, we selected the tyramidyl maslinic acid conjugate (3f or TMA) to determine antitumor capacity over a wide range of cancer cell lines, including glioblastoma, melanoma, breast, lung, colorectal and pancreatic cancer. Our results clearly demonstrated that TMA induced higher cytotoxicity in all cancer cell types compared to MA. TMA was more effective than MA, especially in breast cancer cells (MCF-7) and melanoma cells (B16–F10) where IC50 reductions of 4.12 and 4.72, respectively, was detected. Interestingly, TMA showed a remarkable antitumor ability against the resistant HCT-15 colon cancer cell line. Furthermore, we demonstrated for the first time a relevant effect of a MA derivative against glioblastoma cells (A172 and SF-268). These results suggest that TMA is able to improve the antitumor characteristics of MA in a wide range of cancers and that it may be a promising compound for various tumor types, including resistant cancer.

Microwave-assisted maillard reaction between rice protein and dextran induces structural changes and functional improvements

The effects of microwave treatment Maillard reaction on rice protein (RP) and dextran was investigated. Microwaving accelerated the Maillard reaction between RP and dextran. A solubility of 24.22% was reached by conventional heating for 5 min, whereas microwave treatment obtained a solubility of 64.25% over the same amount of time. The activation energy of the Maillard reaction by microwave treatment was calculated to be 28.52 kJ/mol which is lower than that by conventional heating. Molecular weight analysis and Fourier transform infrared spectroscopy (FTIR) demonstrated that the Maillard reaction induced changes in molecular weight and chemical structure. Spectral analysis showed that the Maillard reaction by microwaving allowed the RP tertiary structure to expand more widely, resulting in better solubility of conjugates. In general, microwave treatment Maillard reaction products (PM) showed higher improvement in functional properties than that of conventional heating Maillard reaction products (PC), this proved that microwave is more capable of improving functional properties. This research demonstrates an efficient method for the processing of RP to improve its functional properties, which can expand its application in the food, cosmetic, and pharmaceutical fields.

Covalent Conjugates of Ammine and Diamine Platinum(II) with Zinc(II) Octacarboxyphthalocyanine

Covalent conjugates of ammine and diamine platinum(II) and octacarboxy substituted zinc phthalocyanine bearing one, two, three and four ammine platinum and ethylenediamine-N,N′-diacetic acid platinum moieties on the periphery of the Pc ligand have been synthesized and characterized. Complexes with two and three ammine platinum fragments and all diamine compounds have been synthesized for the first time. The solubility of conjugates with diamine platinum in aqueous solutions is higher than that for their ammine counterparts and for both series it significantly decreases as the number of platinum atoms increases. The effect of the stepwise introduction of the ammine and diamine platinums on the dynamics of the singlet and triplet excited states, on the ability to sensitize singlet oxygen formation and on the photostability of these compounds has been investigated in dimethylsulfoxide solution. Both ammine and diamine platinum moieties have only a limited effect on the photophysical and photochemical properties. Conjugates sensitize the formation of singlet oxygen with high quantum yields (Φ ∆ =0.47-0.60) and show higher activity in photoinactivation of cancer cells and cytotoxicity than parent octacarboxy-substituted PcZn.

In Vitro and In Vivo Study of Poly(ethylene glycol) Conjugated Ibuprofen to Extend the Duration of Action

Ibuprofen–polyethylene glycol (PEG) conjugates (PEG-Ibu) were prepared and their potential as a prolonged release system was investigated. Two PEG-Ibu conjugates were synthesized from Ibuprofen and PEG with two different molecular weights by esterification in the presence of DCC and DMAP. The PEG-Ibu conjugates were characterized by FT-IR, 1H NMR, Mass spectroscopy and DSC analysis. The solubility study in aqueous system showed an increase in solubility of conjugates. The dissolution / hydrolysis studies showed a specific acid–base catalysis pattern dependent on the pH of the medium. This indicated a good chemical stability in aqueous buffer solution of acidic medium and the extended release behavior was found in both prodrugs after 9 hour. The results demonstrate that, in the same condition, the rate of hydrolysis for PEG4000-Ibu is slower than other. The Writhing induced by acetic acid experiment and paw edema test after oral administration showed that both conjugates had extended analgesic and anti-inflammatory effects compared with Ibuprofen. These results suggest that PEG-Ibu could be a promising NSAID prodrug with an extended pharmacological effect owing to delayed-release of parent drug.