Influence of formulation on photoinactivation of bacteria by lumichrome.

Lumichrome, a photodegradation product of riboflavin, is an endogenous compound in humans. The compound is more photostable and a more efficient photogenerator of singlet oxygen than riboflavin. It absorbs radiation in the UVA and blue-light region, which can be an advantage in antibacterial photodynamic therapy (aPDT) of superficial infections. The aim of this study was to investigate the in vitro aPDT effect of various lumichrome pharmaceutical formulations. Solutions of lumichrome (10(-5) - 10(-3)M) were prepared in plain phosphate buffered saline (PBS) or in PBS solutions containing cyclodextrins, DMSO, PEG 400 or polyoxamers (Pluronic). Supersaturated solutions of lumichrome in PBS were prepared via the cosolvent and solvent evaporation method. Phototoxic effects of selected lumichrome preparations were studied in planktonic Gram-positive (E. faecalis) and Gram-negative (E. coli) bacteria models. The UVA/blue light source emitted mainly in the range 340-440 nm. Lumichrome was up to tenfold more phototoxic against Gram-positive than to Gram-negative bacteria. Bacterial eradication was induced after exposure of lumichrome formulations (PBS, PEG 400 and HPγCD) combined with 24J/cm2 UVA/blue light. Increasing the concentration of lumichrome did not enhance the phototoxic effect, probably due to radiation attenuation in the highly absorbing solution (inner filter effect). Cyclodextrins were efficient enhancers of the lumichrome solubility in aqueous solutions, but inhibited the phototoxic effect. The study demonstrates that assuming the use of an optimized formulation, lumichrome has potential as a UVA/blue light photosensitizer in aPDT.

Investigation of curcumin-cyclodextrin inclusion complexation in aqueous solutions containing various alcoholic co-solvents and alginates using an UV-VIS titration method. Studies of curcumin and curcuminoides, XXXV.

The effect of pharmaceutical excipients like alcoholic co-solvents and water-soluble polymers on the inclusion complexation of curcumin in hydroxypropyl-beta-cyclodextrin and hydroxypropyl-gamma-cyclodextrin was investigated with a UV-VIS titration method. The association constants and the stoichiometries of the inclusion complexes in buffered media containing various amounts dl of alcoholic co-solvents and alginates were determined. The results showed a 1 : 1 stoichiometry between curcumin and both the cyclodextrins investigated in buffered media containing 10% (v/v) alcoholic co-solvents, although some 1 : 2 (host:guest) complexation was suspected between curcumin and hydroxypropyl-beta-cyclodextrin. The presence of 0.1% (w/v) sodium alginate or propylene glycol alginate did apparently not change the stoichiometry of the complexes formed. Curcumin was found to have a more than 30-fold higher association constant with hydroxypropyl-gamma-cyclodextrin compared to hydroxypropyl-beta-cyclodextrin in buffer containing 0.5% ethanol. Large variation in the association constants between curcumin and the cyclodextrins as a result of different co-solvents in the aqueous complexing media were found. A decrease in the association constant was seen as the chain lenght of the added co-solvent increased. Further, a decrease in the association constants was observed by addition of alginates in the case of hydroxypropyl-gamma-cyclodextrin at 0.5 or 5% (v/v) ethanol. The trend was opposite in the case of hydroxypropyl-beta-cyclodextrin, where a 30-90% increase in the association constant was observed in the presence of alginates. The results in the current study showed the large variations in the complexation between curcumin and hydroxypropyl-beta-cyclodextrin and hydroxypropyl-gamma-cyclodextrin, resepctively, as a result of various alcoholic co-solvents and alginates in the complexing media. The results also illustrated the importance of optimizing the solvent systems when utilizing cyclodextrins as drug carriers.

In vitro release of curcumin from vehicles containing alginate and cyclodextrin. Studies of curcumin and curcuminoides. XXXIII.

Combinations of cyclodextrins and alginates were used to solubilize the hydrophobic compound curcumin in aqueous vehicles intended for topical delivery. A careful selection of the excipients is necessary to achieve a sufficient release of curcumin towards a membrane of hydrophilic character, e.g. mucosa. The aim of the study was to investigate the effect of different combinations of cyclodextrins and alginates on curcumin release towards hydrophilic membranes in vitro. The curcumin flux through semi-permeable membranes of different molecular weight cut-off was measured to differentiate between the flux of curcumin in its uncomplexed form (restricted flux), its uncomplexed form together with its inclusion complexes (partly restricted flux) and the overall flux of curcumin-cyclodextrin complexes and uncomplexed curcumin (unrestricted flux). A high viscosity of the vehicle was expected to inhibit curcumin flux. Vehicles containing 3% alginate were found to have lower unrestricted flux than the vehicles containing 0.5% alginate independent of the type of cyclodextrin used. The results indicate that the unrestricted curcumin flux (e.g. in the case of wounded skin) is rather independent of the composition of the hydrophilic vehicle and mostly limited by the viscosity. However, partly restricted and restricted curcumin flux were found to depend on both the viscosity and the composition of the vehicles. The cyclodextrin with the demonstrated lowest solubilisation capacity (i.e. hydroxypropyl-beta-cyclodextrin) resulted in the highest values of both the restricted and unrestricted curcumin flux. In conclusion, a combination of hydroxypropyl-beta-cyclodextrin and propylene glycol alginate seemed to be the best choice with respect to curcumin solubility and release from the vehicle.

Nasal administration of carbamazepine using chitosan microspheres: in vitro/in vivo studies.

The nasal route is used both for local therapies and, more recently, for the systemic administration of drugs, as well as for the delivery of peptides and vaccines. In this study the nasal administration of Carbamazepine (CBZ) has been studied using microspheres constituted by chitosan hydrochloride (CH) or chitosan glutamate (CG). Blank microspheres were also prepared as a comparison. The microspheres were produced using a spray-drying technique and characterized in terms of morphology (scanning electron microscopy, SEM), drug content, particle size (laser diffraction method) and thermal behaviour (differential scanning calorimetry, DSC). In vitro drug release studies were performed in phosphate buffer (pH 7.0). In vivo tests were carried out in sheep using the microparticles containing chitosan glutamate, chosen on the basis of the results of in vitro studies. The results were compared to those obtained after the nasal administration of CBZ (raw material) alone. For the evaluation of in vivo data statistical analysis was carried out using the unpaired t-test. Spray-drying was a good technique of preparation of CBZ-loaded microspheres. The loading of the drug into the polymeric network always led to an increase in the dissolution rate compared to CBZ raw material. The microspheres obtained using chitosan glutamate had the best behaviour both in vitro and in vivo. They increased the drug concentration in the serum when compared to the nasal administration of the pure drug (Cmax 800 and 25 ng/ml for microspheres and pure drug, respectively). The results obtained indicate that the loading of CBZ in chitosan glutamate microspheres increases the amount of the drug absorbed through the nose.