Chitosan-Based Nanoparticles for Targeted Nasal Galantamine Delivery as a Promising Tool in Alzheimer's Disease Therapy.

Natural alkaloid galantamine is widely used for the treatment of mild to moderate Alzheimer's dementia. Galantamine hydrobromide (GH) is available as fast-release tablets, extended-release capsules, and oral solutions. However, its oral delivery can cause some unwanted side effects, such as gastrointestinal disturbances, nausea, and vomiting. Intranasal administration is one possible way to avoid such unwanted effects. In this work, chitosan-based nanoparticles (NPs) were studied as potential GH delivery vehicles for nasal application. The NPs were synthesized via ionic gelation and studied using dynamic light scattering (DLS) as well as by spectroscopic and thermal methods. The GH-loaded chitosan-alginate complex particles were also prepared as a way to modify the release of GH. The high loading efficiency of the GH was confirmed for both types of particles, at 67% for the GH-loaded chitosan NPs and 70% for the complex chitosan/alginate GH-loaded particles. The mean particle size of the GH-loaded chitosan NPs was about 240 nm, while the sodium alginate coated chitosan particles loaded with GH were expectedly bigger, with a mean particle size of ~286 nm. GH release profiles in PBS at 37 °C were obtained for both types of NPs, and it was found that the GH-loaded chitosan NPs allowed the prolonged release of the incorporated drug for a period of 8 h, while the complex GH-loaded chitosan/alginate NPs released the incorporated GH faster. The stability of the prepared GH-loaded NPs was also demonstrated after 1 year of storage at 5 °C ± 3 °C.

Poly(Sulfobetaine Methacrylate-co-Vinyl Pyrrolidone) Hydrogels as Potential Contact Lenses Delivery Systems for Timolol Maleate.

The study reveals the development of novel hydrogels based on sulfobetaine methacrylate (SB) and vinyl pyrrolidone (VP) copolymers as potential contact lenses delivery systems of timolol maleate (TM). The novel copolymer networks demonstrated composition dependent swelling kinetics, where the hydrophilicity of VP and the physical network of SB monomeric units play significant roles. TM loading efficiency appeared to slightly depend on the copolymeric composition, increasing upon VP monomeric unit increase. In contrast, the TM release was prolonged when the SB monomeric units content in the copolymers increased, reaching full drug release for 48 h for the SB-rich networks. The transparency of the hydrogels was also studied and the obtained values demonstrate their applicability as potential materials for soft contact lenses. The study has revealed the potential of these novel copolymeric hydrogels as materials for contact lenses delivery systems of timolol maleate.

Absolute quantification of selected photosynthetic electron transfer proteins in Chlamydomonas reinhardtii in the presence and absence of oxygen.

The absolute amount of plastocyanin (PC), ferredoxin-NADP+-oxidoreductase (FNR), hydrogenase (HYDA1), and ferredoxin 5 (FDX5) were quantified in aerobic and anaerobic Chlamydomonas reinhardtii whole cells using purified (recombinant) proteins as internal standards in a mass spectrometric approach. Quantified protein amounts were related to the estimated amount of PSI. The ratios of PC to FNR to HYDA1 to FDX5 in aerobic cells were determined to be 1.4:1.2:0.003:0. In anaerobic cells, the ratios changed to 1.1:1.3:0.019:0.027 (PC:FNR:HYDA1:FDX5). Employing sodium dithionite and methyl viologen as electron donors, the specific activity of hydrogenase in whole cells was calculated to be 382 ± 96.5 µmolH2 min-1 mg-1. Importantly, these data reveal an about 70-fold lower abundance of HYDA1 compared to FNR. Despite this great disproportion between both proteins, which might further enhance the competition for electrons, the alga is capable of hydrogen production under anaerobic conditions, thus pointing to an efficient channeling mechanism of electrons from FDX1 to the HYDA1.

Temperature-Induced Remodeling of the Photosynthetic Machinery Tunes Photosynthesis in the Thermophilic Alga Cyanidioschyzon merolae.

The thermophilic alga C. merolae thrives in extreme environments (low pH and temperature between 40°C and 56°C). In this study, we investigated the acclimation process of the alga to a colder temperature (25°C). A long-term cell growth experiment revealed an extensive remodeling of the photosynthetic apparatus in the first 250 h of acclimation, which was followed by cell growth to an even higher density than the control (grown at 42°C) cell density. Once the cells were shifted to the lower temperature, the proteins of the light-harvesting antenna were greatly down-regulated and the phycobilisome composition was altered. The amount of PSI and PSII subunits was also decreased, but the chlorophyll to photosystems ratio remained unchanged. The 25°C cells possessed a less efficient photon-to-oxygen conversion rate and require a 2.5 times higher light intensity to reach maximum photosynthetic efficiency. With respect to chlorophyll, however, the photosynthetic oxygen evolution rate of the 25°C culture was 2 times higher than the control. Quantitative proteomics revealed that acclimation requires, besides remodeling of the photosynthetic apparatus, also adjustment of the machinery for protein folding, degradation, and homeostasis. In summary, these remodeling processes tuned photosynthesis according to the demands placed on the system and revealed the capability of C. merolae to grow under a broad range of temperatures.

Deletion of Proton Gradient Regulation 5 (PGR5) and PGR5-Like 1 (PGRL1) proteins promote sustainable light-driven hydrogen production in Chlamydomonas reinhardtii due to increased PSII activity under sulfur deprivation.

Continuous hydrogen photo-production under sulfur deprivation was studied in the Chlamydomonas reinhardtii pgr5 pgrl1 double mutant and respective single mutants. Under medium light conditions, the pgr5 exhibited the highest performance and produced about eight times more hydrogen than the wild type, making pgr5 one of the most efficient hydrogen producer reported so far. The pgr5 pgrl1 double mutant showed an increased hydrogen burst at the beginning of sulfur deprivation under high light conditions, but in this case the overall amount of hydrogen produced by pgr5 pgrl1 as well as pgr5 was diminished due to photo-inhibition and increased degradation of PSI. In contrast, the pgrl1 was effective in hydrogen production in both high and low light. Blocking photosynthetic electron transfer by DCMU stopped hydrogen production almost completely in the mutant strains, indicating that the main pathway of electrons toward enhanced hydrogen production is via linear electron transport. Indeed, PSII remained more active and stable in the pgr mutant strains as compared to the wild type. Since transition to anaerobiosis was faster and could be maintained due to an increased oxygen consumption capacity, this likely preserves PSII from photo-oxidative damage in the pgr mutants. Hence, we conclude that increased hydrogen production under sulfur deprivation in the pgr5 and pgrl1 mutants is caused by an increased stability of PSII permitting sustainable light-driven hydrogen production in Chlamydomonas reinhardtii.