Molecular Targeting and Novel Therapeutic Approaches against Fungal Infections.

BACKGROUND: Fungal infections have become a worldwide problem due to their involvement in numerous diseases. The risk factors for fungal infections are multiple surgeries, transplant therapies, frequent administration of antibiotics, cancer treatments, and prosthetic devices. The problem of resistance in fungi against drug therapies is widespread, becoming a severe health-related problem. OBJECTIVE: The study's objective was to identify molecular targets that may open new paths for fungal treatment. METHODS: Several research and review articles were studied to gather information regarding the novel mechanism of antifungal drugs. However, identifying novel targets is challenging due to the similarities between host and fungal cells. Although, the plasma membrane and cell wall of fungus offer various drug targets that may target to fight against microbial infections. Unfortunately, biofilm formation and over-expression of protein are a few mechanisms through which fungi develop resistance. RESULTS: Despite these problems, several approaches have been working to prevent and treat fungal infections. Modifying the chemical structure of antifungal drugs may also improve their activity and pharmacokinetics. In this review article, we have discussed the molecular targets and novel techniques to be used for the development of antifungal drugs. In addition, different strategies to overcome resistance in fungi have also been described. CONCLUSION: This article may be helpful for the researchers working on the discovery and development of new antifungal works for resistance to fungal diseases.

Pharmacokinetic Parameters Determination and In Vitro-In Vivo Correlation of Ileocolonic-Targeted pH-Responsive Coated Mini-Tablets of Naproxen.

This research work aims to determine the pharmacokinetic parameters and in vitro-in vivo correlation of the selected ileocolonic-targeted coated mini-tablet filled capsule formulation of naproxen. The pure suspension and coated mini-tablet filled capsule formulation of naproxen were administered to adult albino rabbits through the oral route. The samples were analyzed for naproxen by an HPLC method. For the pure drug suspension, the peak plasma concentration was found as 8.499±0.029 µg/ml at 1.139±0.010 hours and the half-life was found to be 9.459±0.387 hours, whereas for the formulation the peak plasma concentration was found as 6.814±0.037 µg/ml at 8.042±0.069 hours and the half-life was found to be 19.657±0.359 hours. This decreased the peak plasma concentration at a delayed time and increased the half-life of the capsule formulation in comparison with the pure drug suspension which showed that naproxen was only targeted to the ileocolonic region. A significant in vitro-in vivo correlation (i.e. R(2)=0.9901) was also obtained. Thus, the results of these findings suggest that naproxen formulated as coated mini-tablets can be suitable for targeted ileocolonic drug delivery.

Matrix-mini-tablets of lornoxicam for targeting early morning peak symptoms of rheumatoid arthritis.

OBJECTIVES: The aim of present research was to develop matrix-mini-tablets of lornoxicam filled in capsule for targeting early morning peak symptoms of rheumatoid arthritis. MATERIALS AND METHODS: Matrix-mini-tablets of lornoxicam were prepared by direct compression method using microsomal enzyme dependent and pH-sensitive polymers which were further filled into an empty HPMC capsule. To assess the compatibility, FT-IR and DSC studies for pure drug, polymers and their physical mixture were performed. The formulated batches were subjected to physicochemical studies, estimation of drug content, in vitro drug release, drug release kinetics, and stability studies. RESULTS: When FTIR and DSC studies were performed it was found that there was no interaction between lornoxicam and polymers which used. All the physicochemical properties of prepared matrix-mini-tablets were found to be in normal limits. The percentage of drug content was found to be 99.60±0.07%. Our optimized matrix mini-tablets-filled-capsule formulation F30 released lornoxicam after a lag time of 5.02±0.92 hr, 95.48±0.65 % at the end of 8 hr and 99.90±0.83 % at the end of 12 hr. Stability was also found for this formulation as per the guidelines of International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. CONCLUSION: A novel colon targeted delivery system of lornoxicam was successfully developed by filling matrix-mini-tablets into an empty HPMC capsule shell for targeting early morning peak symptoms of rheumatoid arthritis.