Vitamin D Pretreatment Attenuates Ciprofloxacin-Induced Antibacterial Activity.

BACKGROUND: Ciprofloxacin is an antimicrobial that is commonly used to treat several types of infections. It exerts its antimicrobial activity through interfering with bacterial DNA replication and transcription, leading to increase oxidative stress and eventually bacterial death. Vitamin D, on the other hand, has been found to have DNA protective and antioxidant effects. In the current study, the possible interactive effect of vitamin D on ciprofloxacin-induced cytotoxicity was investigated in various standard bacterial strains. METHODS: The bacterial strains that were used include Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, Acinetobacter baumannii, Proteus mirabilis, and Klebsiella pneumoniae. The antibacterial effect of ciprofloxacin with and without vitamin D treatment of the bacteria was assessed using disc diffusion method and by measuring the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. Moreover, reactive oxygen species (ROS) generation after pretreatment of E. Coli cells with ciprofloxacin and/or vitamin D was measured as a function of as a function of hydrogen peroxide generation. RESULTS: Ciprofloxacin demonstrated a potent antibacterial effect against the tested strains of bacteria. Moreover, pretreatment with vitamin D resulted in protecting the bacteria from the cytotoxicity of ciprofloxacin, this was indicated by the significantly smaller zones of inhibition and higher MIC values compared to ciprofloxacin alone as well as reduced ciprofloxacin-induced ROS generation after treatment with vitamin D. CONCLUSION: Results revealed the possible reduction in the activity of ciprofloxacin when used in combination with vitamin D. This could be explained by the ability of vitamin D to reduce oxidative stress in the bacterial cells.

Delivery of Peptidic Gonadotropin Releasing Hormone Antagonists.

GnRH antagonists have several clinical applications in prostate cancer, regulation of ovulation induction in females, breast cancer, male contraception and others. Antagonists differ from natural GnRH decapeptide in having five or more amino acid substitutions, whereas most of the antagonists are available as subcutaneous (SC) formula for injection some are formulated as a depot formulation for sustained release (e.g., Cetrorelix, Degarelix). Systemic delivery of cetrorelix acetate by intratracheal route can be achieved using dry powder for inhalation of the adhesive mixture when the powder deposition reaches stage four. The oral route for systemic delivery of peptide without its degradation can be achieved using gastrointestinal permeation enhancement technology GIPET® provided by acyline.

Preparation and characterization of microemulsion formulations of nicotinic acid and its prodrugs for transdermal delivery.

At pharmacological doses, nicotinic acid has a lipid-regulating effect and is in use clinically for that purpose. However, despite of all features, its utility is strongly limited by several disadvantages such as, extensive hepatic metabolism and flushing. Transdermal delivery of nicotinic acid may, therefore, be the solution to reducing side effects associated with oral administration, and to maintaining constant therapeutic blood levels for longer duration. The aim of this investigation was to develop a suitable formulation or select a suitable vehicle for the transdermal delivery of highly lipophilic prodrugs of nicotinic acid (dodecyl and myristyl nicotinate) designed to deliver nicotinic acid through skin without causing vasodilatation and flushing and optimizing its delivery to the blood stream. A microemulsion system and penetration enhancers have been attempted in this study. The microemulsion system was composed of isopropyl myristate (IPM), water and a 4:1 (w/w) mixture of Labrasol and Peceol where a pseudoternary phase diagram was constructed. Furthermore, the microemulsion formulations with different component ratios were characterized by determination of conductivity, pH, particle size, viscosity and refractive index. According to the particle size analysis, conductivity and viscosity measurements, the microemulsion formulations that formed were of oil-in-water type. The transdermal permeability of nicotinic acid and its prodrugs was evaluated in vitro using Franz diffusion cells fitted with mice skin and nicotinic acid concentration was analyzed by high performance liquid chromatography. A theoretical design of percutaneous penetration optimization in which prodrugs derivation and enhancer application are combined based on the skin diffusion model was experimentally verified. The selected formulations seemed promising for developing a transdermal drug delivery system of nicotinic acid from dodecyl nicotinate that would offer advantages like possible controlled drug release, reduced flushing, increased drug stability and ease of large-scale production.

Effect of microenvironment pH of swellable and erodable buffered matrices on the release characteristics of diclofenac sodium.

The aim of this work is to design pH-dependent swellable and erodable-buffered matrices and to study the effect of the microenvironment pH on the release pattern of diclofenac sodium. Buffered matrix tablets containing diclofenac sodium, physically mixed with hydrophilic polymer (hydroxypropyl methylcellulose [HPMC]) and pH-dependent solubility polymer (Eudragit L100-55) were prepared with different microenvironment pHs. The release of diclofenac sodium from the buffer matrices was studied in phosphate buffer solutions of pH 5.9 and 7.4. The swelling and erosion matrices containing only HPMC and Eudragit L100-55 were studied in phosphate buffer solution of pH similar to the microenvironment pHs of the matrices. Drug release from matrices was found to be linear as a function of time. Amount of drug released was found to be higher in the medium of pH 7.4 than that of pH 5.9. The rate of drug release increased with the increase of the microenvironment pH of the matrices as determined from the slope. The pattern of drug release did not change with the change of microenvironment pH. The swelling and erosion occurred simultaneously from matrices made up of HPMC and Eudragit L100-55. Both extent of swelling and erosion increased with increase of the medium pH. It was concluded from this study that changing the pH within the matrix influenced the rate of release of the drug without affecting the release pattern.