Size-switchable polymer-based nanomedicines in the advanced therapy of rheumatoid arthritis.

Chronic inflammatory diseases such as rheumatoid arthritis represent a substantial socio-economic impact and have a high prevalence in the modern world. Nano-sized polymer therapeutics have shown suitable characteristics for becoming the next generation of anti-inflammatory nanomedicines. Here, we present biocompatible and stimuli-sensitive N-(2-hydroxypropyl)methacrylamide based polymer conjugates with the anti-inflammatory drug dexamethasone (DEX), which has been tailored for prolonged blood circulation, enhanced inflammatory site accumulation, site-specific drug release and subsequent elimination of the carrier via urine excretion. The hydrodynamic size of novel polymer-DEX nanomedicine was adjusted to prolong its blood circulation whilst maintaining the renal excretability of the polymer carrier after drug release in inflamed tissue. The therapeutic efficacy of the studied polymer nanomedicines was evaluated in a model of dissipated chronic arthritis, i.e. collagen II-induced arthritis, in mice. The pH-sensitive drug attachment enabled enhanced blood circulation with minimal systemic drug release, as well as rapid drug activation in affected joints. Importantly, unlike free DEX, the polymer nanomedicines were able to diminish joint inflammation and arthritis-induced bone damage - even at a reduced dosing regimen - as evaluated by micro computed tomography (micro-CT).

Combination effect with some aminoglycoside antibiotics.

Strains of resistant species -- Staphylococcus aureus and Streptococcus faecalis -- isolated from material of nosocomial infections in the surgical department of a Prague hospital were tested for combined effect with further chemotherapeutics. The same concerned Ps, aeruginosa noted, at present, by a high degree of resistance. In Ps. aeruginosa it was the combination sisomicin-carfecillin that proved a success in 50 p. c. of cases as well as that of sisomicin-doxycyclin. At the same time the authors draw attention to the possibility of antagonistic action of the combination sisomicin-chloramphenicol in a third part of the strains tested. Potentiation of the effect in Staphylococcus aureus strains was observed also in the combination sisomicin-carfecillin in more than one half of the strains tested and in case of sisomicin-doxycyclin in one third of the strains. In Streptococcus faecalis strains sisomicin was combined with amoxycillin, carbenicillin, carfecillin and doxycyclin; synergistic action being observed with all those combinations in more than one half of strains tested. No antagonism was registered in those cases. (Ta.).