Indomethacin functionalised poly(glycerol adipate) nanospheres as promising candidates for modified drug release.

The linear polyester poly(glycerol adipate) (PGA) with its free pendant hydroxyl groups was covalently grafted with indomethacin which yields polymeric prodrugs. It was possible to produce nanospheres with narrow particle size distribution of these polymer-drug conjugates with an optimized interfacial deposition method. Nanospheres were characterized by zeta potential measurements, dynamic light scattering, electron microscopy and nanoparticle tracking analysis. Moreover, cell viability studies and cytotoxicity tests in three different cell lines were carried out showing low toxicity for three different degrees of grafting. In addition, the nanospheres had (in contrast to the free drug) low hemolytic activity in vitro. Release studies of nanodispersions are challenging. The use of a specially developed setup with highly porous aluminum oxide membranes enabled us to overcome problems associated with other setups (e.g. dialysis membranes). A slow and controlled release profile without any burst was observed over 15 days. The results indicate that indomethacin-PGA conjugates can be formulated successfully as nanospheres with the desired characteristics of small size with narrow distribution, controlled drug release and low toxicity. The newly developed particles have the potential to improve the therapy of inflammation and associated diseases.

[A comparison of different types of suburethral slings in the treatment of urinary incontinence in geriatric patients]. / Srovnání ruzných typu pásek v lécbe inkontinence moci u gerontologických pacientek.

OBJECTIVE: Comparison of different types of tension free tapes in the treatment of urinary incontinence in institutionalized elderly patients. DESIGN: Prospective randomized study. SETTING: Charles University in Prague, 1st Medical Faculty and Hospital Bulovka, Department of Obstetrics and Gynaecology, Prague. METHODS: 43 patients of several gerontologic centres with prevailing stress urinary incontinence were included based on urinary dysfunction specific questionnaire (ICIQ) and cognitive functions objective estimation (MMSE). Three types of tapes, TVT-O, MiniArc and Ajust were used and patients were randomized into the groups and after an urogynaecologic examination, incl. ultrasound the operation was performed. RESULTS: The groups were - except of the age of the patients of group MiniArc - well outweighted concerning demographic parameters. High success rate of all techniques used evaluated by the QoL questionnaires was in all the groups comparable. No case of bleeding, bladder injury or postoperative pain was found. Higher frequency of OAB de novo and worsening of preexisting symptomatics could be explained by general very high prevalence of OAB in the elderly even without the operation. In whole our cohort only 1 case of failure to treat and of tape exposure was found. Our results confirming high success rate of all the types also in elderly and institutionalized patients are in consent with sporadic published data. CONCLUSION: Surgical treatment of cases of stress and mixed urinary incontinence is also in cases of elderly polymorbid nurcing facilities clients with regard to the high success rate. Secondary outcome of our report when accepting the conclusion is drop of the costs of antiincontinence pads thus having a significant economic effect.

Production of Forskolin by Axenic Coleus forskohlii Roots Cultivated in Shake Flasks and 20-l Glass Jar Bioreactors*.

Root cultures of COLEUS FORSKOHLII Briq. were initiated from primary callus or IBA-treated suspension cultures and maintained on Gamborg's B5 medium containing 1 mg/l IBA. Transformed root cultures were established by infecting surface-sterilized leaves with AGROBACTERIUM RHIZOGENES strain 15834. Transformation was confirmed by mannopine detection. These cultures displayed the typical characteristics of hairy root cultures, with the sole exceptions of slow growth in hormone-free medium and accelerated growth on medium containing phytohormones. All root cultures examined formed forskolin and its derivatives in amounts ranging from 500 to 1300 mg/kg dry weight, corresponding to about 4 to 5 mg/l. During cultivation roots could be cut into small pieces without affecting growth and forskolin production. Scale-ups of the cultivation procedure were performed in 20-l glass jars with a working volume of 10 to 13l. Forskolin production in bioreactors was better than in shake flasks. Levels of almost 14 mg/l could be reached after 21 d of cultivation. As in the shake flask experiments cutting the roots did not affect growth or productivity in a negative way.