Objectives Patient medication compliance can be seriously affected by a bitter taste. There are various taste-masking agents, but they urgently need to be improved. Mesoporous molecular sieves are a type of 3-dimensional nanostructure that has a regular pore diameter (2–50 nm), has a large surface area, and is non-toxic. These structures are widely used in biomedicine but their application in the drug taste-masking field has not previously been reported. The objective of this investigation was to prepare three different mesoporous molecular sieves (MCM-41, MCM-48 and HMSS) and to determine their masking properties through volunteer tasting. Methods MCM-41, MCM-48 and HMSS were synthesized using a hydrothermal method. The bitter-tasting drug cetirizine (CTH) was used as the model drug. CTH-sieve composites were prepared using the impregnation method and the composites were characterized by means of XRD, FTIR, nitrogen physical adsorption and TGA. Three commonly used taste-masking agents were used as contrast to mask the bitter flavor of CTH. Results MCM-41, MCM48 and HMSS showed a large CTH loading capacity of 25.12%, 32.91% and 50.00%, respectively, and effectively reduced the bitter taste of CTH by covering the oral mucous membrane thus reducing irritation. Conclusions The pore structure and large surface area of the sieves improved taste-masking efficiency compared with common taste-masking agents. Mesoporous molecular sieves have the potential to increase the efficacy of taste-masking agents. Acknowledgments This research was financially supported by Jilin Provincial Development and Reform Commission Industrial Technology Research and Development Funds (Grant No. 2014Y091).
Objectives We designed a series of formulations of rhGH PK3/PLGA microspheres with different PK3/PLGA ratios to improve the stability and incomplete release of rhGH with the aim of achieving long-acting sustained-release rhGH microspheres. PK3 can undergo acid-catalyzed hydrolysis into low molecular weight hydrophilic compounds and release encapsulated drugs at an accelerated rate in acidic environments. PK3/PLGA microspheres effectively avoided the influence of the acidic environment produced by the degradation of PLGA on rhGH stability and solved the problem of difficult release of denaturated rhGH. The microspheres improved the poor mechanical properties of PK3 microspheres due to low molecular weights. Methods We used a W/O/W double-emulsion technique to prepare rhGH microspheres. Briefly, 100 µL of 40 mg/mL rhGH was dissolved in 2 mL of acetone/methylene chloride solution (0.8:1.2) containing PK3/PLGA blends and homogenized at 6000 rpm for 120 s in an ice bath. The primary emulsion was injected into an aqueous solution containing 0.5% (w/v) PVA and 3% (w/v) NaCl and homogenized at 6000 rpm for 120 s. Microspheres were obtained by evaporating the organic solvents and centrifuging at 5000 rpm. We investigated the effects of different PK3/PLGA ratios (10:0, 8:2, 6:4, 5:5, 4:6, 2:8, 0:10) and the buffer pH value (pH 4.5, pH 7.4) on the in vitro release of rhGH microspheres. We studied the structural stability of rhGH in release medium and inside the microspheres. Results Native PAGE results revealed the microspheres displaying enhanced structural stability of rhGH with a neutral microenvironment compared with PLGA microspheres. With an increase in PK3 ratios, the microspheres showed reduced incomplete release and increased total release of rhGH. When the PK3/PLGA ratios were above PK3-PLGA mass ratio 5:5, the mixing microspheres had a low balling rate and irregular form. Conclusions The optimal ratio of PK3/PLGA was 3:7, producing significant rhGH stability and an in vitro release profile with less burst release and extended sustained release.
Objectives Nanoscaled drug carriers with pH-responsiveness have attracted extensive interest in view of the acidic environment in cancerous cells. Rapid response to pH changes plays a key role in efficient intracellular drug release. In addition, real-time tracking of drug carriers is important for understanding distribution and targeted accumulation of the drug carriers. This work aims at developing silver selenide quantum dots (Ag 2 Se QDs)@carboxymethyl chitosan (CMCS) core-shell nanospheres with encapsulated paclitaxel (PTX) for cancer therapy and bioimaging. Methods Oleic acid-capping Ag 2 Se QDs were synthesized by a one-pot strategy, washed with ethanol, and obtained by centrifugation. The as-synthesized Ag 2 Se QDs were reacted with N-hydroxysuccinimide and conjugated with CMCS at the amino sites. In an aqueous solution of PTX, the hydrophobic oleoyl groups tended to aggregate locally and entrap PTX by hydrophobic interaction, spontaneously producing Ag 2 Se QDs (PTX)@CMCS nanospheres. Results By conjugating the oleic acid-capping Ag 2 Se QDs with pH-sensitive CMCS at a degree of substitution (DS) of 13%, biocompatible core-shell nanospheres loaded with PTX were successfully prepared, which had an average size of 36.3 ± 0.2 nm. The drug loading content (DLC) and drug loading efficiency (DLE) for the PTX was 5.01 ± 0.8% and 52.4 ± 3.2%, respectively. The PTX release half-life was 4.1 hours under conditions resembling the intracellular environment of cancerous cells (37°C, pH 5.0). Conclusions Core-shell structured Ag 2 Se QDs (PTX)@CMCS nanospheres capable of releasing PTX in an acidic environment and emitting NIR fluorescence under NIR laser excitation were synthesized and characterized. The hydrophobic oleoyl groups entrapped PTX via hydrophobic interaction and the oleoyl-CMCS chains were extended at lowered pH to release the otherwise encaged drug. In addition, the encapsulated Ag 2 Se QDs can emit bright NIR fluorescence for bioimaging by which nanosphere distribution in a patient can be monitored. This study provides a new approach for developing nanocomposite drug carriers for cancer therapy.
Rapid putative radiations of Rheum might be caused by the recent uplifts of the Qinghai–Tibetan Plateau and the quaternary climate oscillations. To better understand the molecular adaptation associated with Rheum radiation, in this study, the adaptive evolution of the chloroplast rbcL gene was analysed using the Phylogenetic Analysis Program. The results showed that two amino acid residues (75F, 203I) were under positive selection. The spatial analysis indicated that the site (75F) was located in the β-sheet of the N-terminal loops involved in subunit interactions in the L8S8 molecule, and the site (203I) was in the α/β-barrel active centre located on the C-terminal domain of the large subunit of Rubisco. These results suggest that potential positive selection in rbcL might have played an important role in the adaption of Rheum species to the extreme environments in Qinghai–Tibetan Plateau regions, and different species lineages might have been subjected to different selective pressures.
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