A Water-Soluble Chitosan Derivative for the Release of Bioactive Deferoxamine.

Deferoxamine (DFO) is a water-soluble iron chelator used pharmacologically for the management of patients with transfusional iron overload. However, DFO is not cell-permeable and has a short plasma half-life, which necessitates lengthy parenteral administration with an infusion pump. We previously reported the synthesis of chitosan (CS) nanoparticles for sustained slow release of DFO. In the present study, we developed solid dispersions and nanoparticles of a carboxymethyl water-soluble chitosan derivative (CMCS) for improved DFO encapsulation and release. CS dispersions and nanoparticles with DFO have been prepared by ironical gelation using sodium triphosphate (TPP) and were examined for comparison purposes. The successful presence of DFO in CMCS polymeric dispersions and nanoparticles was confirmed through FTIR measurements. Furthermore, the formation of CMCS nanoparticles led to inclusion of DFO in an amorphous state, while dispersion of DFO in the polymeric matrix led to a decrease in its crystallinity according to X-ray diffraction (XRD) and differential scanning calorimetry (DSC) results. An in vitro release assay indicated sustained release of DFO from CS and CMCS nanoparticles over 48 h and 24 h, respectively. Application of CMCS-DFO dispersions to murine RAW 264.7 macrophages or human HeLa cervical carcinoma cells triggered cellular responses to iron deficiency. These were exemplified in the induction of the mRNA encoding transferrin receptor 1, the major iron uptake protein, and the suppression of ferritin, the iron storage protein. Our data indicate that CMCS-DFO nanoparticles release bioactive DFO that causes effective iron chelation in cultured cells.

Inhibition of Cancer Cell Proliferation and Bacterial Growth by Silver(I) Complexes Bearing a CH3-Substituted Thiadiazole-Based Thioamide.

Ag(I) coordination compounds have recently attracted much attention as antiproliferative and antibacterial agents against a wide range of cancer cell lines and pathogens. The bioactivity potential of these complexes depends on their structural characteristics and the nature of their ligands. Herein, we present a series of four Ag(I) coordination compounds bearing as ligands the CH3-substituted thiadiazole-based thioamide 5-methyl-1,3,4-thiadiazole-2-thiol (mtdztH) and phosphines, i.e., [AgCl(mtdztH)(PPh3)2] (1), [Ag(mtdzt)(PPh3)3] (2), [AgCl(mtdztH)(xantphos)] (3), and [AgmtdztH)(dppe)(NO3)]n (4), where xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and dppe = 1,2-bis(diphenylphosphino)ethane, and the assessment of their in vitro antibacterial and anti-cancer efficiency. Among them, diphosphine-containing compounds 3 and 4 were found to exhibit broad-spectrum antibacterial activity characteristics against both Gram-(+) and Gram-(-) bacterial strains, showing high in vitro bioactivity with IC50 values as low as 4.6 µΜ. In vitro cytotoxicity studies against human ovarian, pancreatic, lung, and prostate cancer cell lines revealed the strong cytotoxic potential of 2 and 4, with IC50 values in the range of 3.1-24.0 µΜ, while 3 and 4 maintained the normal fibroblast cells' viability at relatively higher levels. Assessment of these results, in combination with those obtained for analogous Ag(I) complexes bearing similar heterocyclic thioamides, suggest the pivotal role of the substituent groups of the thioamide heterocyclic ring in the antibacterial and anti-cancer efficacy of the respective Ag(I) complexes. Compounds 1-4 exhibited moderate in vitro antioxidant capacity for free radicals scavenging, as well as reasonably strong ability to interact with calf-thymus DNA, suggesting the likely implication of these properties in their bioactivity mechanisms. Complementary insights into the possible mechanism of their anti-cancer activity were provided by molecular docking calculations, exploring their ability to bind to the overexpressed fibroblast growth factor receptor 1 (FGFR1), affecting cancer cells' functionalities.

Poly(Lactic Acid)-Based Microparticles for Drug Delivery Applications: An Overview of Recent Advances.

The sustained release of pharmaceutical substances remains the most convenient way of drug delivery. Hence, a great variety of reports can be traced in the open literature associated with drug delivery systems (DDS). Specifically, the use of microparticle systems has received special attention during the past two decades. Polymeric microparticles (MPs) are acknowledged as very prevalent carriers toward an enhanced bio-distribution and bioavailability of both hydrophilic and lipophilic drug substances. Poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), and their copolymers are among the most frequently used biodegradable polymers for encapsulated drugs. This review describes the current state-of-the-art research in the study of poly(lactic acid)/poly(lactic-co-glycolic acid) microparticles and PLA-copolymers with other aliphatic acids as drug delivery devices for increasing the efficiency of drug delivery, enhancing the release profile, and drug targeting of active pharmaceutical ingredients (API). Potential advances in generics and the constant discovery of therapeutic peptides will hopefully promote the success of microsphere technology.

Poly(lactic Acid): A Versatile Biobased Polymer for the Future with Multifunctional Properties-From Monomer Synthesis, Polymerization Techniques and Molecular Weight Increase to PLA Applications.

Environmental problems, such as global warming and plastic pollution have forced researchers to investigate alternatives for conventional plastics. Poly(lactic acid) (PLA), one of the well-known eco-friendly biodegradables and biobased polyesters, has been studied extensively and is considered to be a promising substitute to petroleum-based polymers. This review gives an inclusive overview of the current research of lactic acid and lactide dimer techniques along with the production of PLA from its monomers. Melt polycondensation as well as ring opening polymerization techniques are discussed, and the effect of various catalysts and polymerization conditions is thoroughly presented. Reaction mechanisms are also reviewed. However, due to the competitive decomposition reactions, in the most cases low or medium molecular weight (MW) of PLA, not exceeding 20,000-50,000 g/mol, are prepared. For this reason, additional procedures such as solid state polycondensation (SSP) and chain extension (CE) reaching MW ranging from 80,000 up to 250,000 g/mol are extensively investigated here. Lastly, numerous practical applications of PLA in various fields of industry, technical challenges and limitations of PLA use as well as its future perspectives are also reported in this review.