ABSTRACT
This paper presents the synthesis and characterization of gellan gum derivatives containing quaternary ammonium groups, with the purpose of obtaining particulate controlled release systems for ciprofloxacin. Quaternized gellan derivatives were synthesized by grafting N-(3-chloro-2-hydroxypropyl)-trimethyl ammonium chloride onto gellan primary hydroxyl groups by nucleophilic substitution, in the presence of alkali, under specific reaction conditions using various gellan/N-(3-chloro-2-hydroxypropyl)-trimethyl ammonium chloride molar ratios. Degree of quaternization was determined by (1)H NMR spectroscopy and AgNO3 conductometric titration. Thermal behavior was investigated for all materials by thermogravimetric analysis. A study of the degree of quaternization and effect of the reaction conditions upon activation energy of quaternized gellan derivatives for the main degradation step by applying the Kissinger method at four heating rates is also reported. The novelty that this work brings refers to obtaining quaternized gellan and chitosan based particles with retention of quaternary ammonium moieties' antibacterial activity. In vitro transdermal release tests of ciprofloxacin from loaded particles were carried out on rat skin in isotonic phosphate buffer solution (pH=7.43). Ciprofloxacin was released up to 24 h, confirming quaternized gellan-chitosan particles' potential as controlled release systems for topical dermal applications.
Subject(s)
Bacterial Physiological Phenomena/drug effects , Ciprofloxacin/administration & dosage , Ciprofloxacin/pharmacokinetics , Delayed-Action Preparations/chemical synthesis , Polysaccharides, Bacterial/chemistry , Quaternary Ammonium Compounds/chemical synthesis , Skin Absorption/physiology , Administration, Topical , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacokinetics , Cell Survival/drug effects , Ciprofloxacin/chemistry , Delayed-Action Preparations/administration & dosage , Diffusion , Materials Testing , RatsABSTRACT
We studied the potentially bronhodilatatory action of some new xanthine compounds, theophylline derivatives with 7-[2-hydroxy-3-(4-acetamido)-phenoxy-propyl]-8-R-1,3-dimethyl-xanthine and 8-R-1,3-bis-(1,3-dimethyl-xanthin-7yl)-2-hydroxy-propane structure substituted in 7 and 8 position. The tracheal smooth muscle contraction we realized by carbachol (10(-5) M) or potassium chloride (40 mM), the xanthine compound being much active on the contraction induced by carbachol. We observed that the modification realised in theophylline structure determined the modification of bronchodilatatory properties. The bronchodilatatory effect of theophylline intensified with the introduction in 7 position the 2-hydroxy-3-(acetamido)-phenoxy-propyl and in 8 position the bromo, nitro, piperidinyl and imidazolyl radicals.
