Current Issue : July-September Volume : 2022 Issue Number : 3 Articles : 5 Articles
Backgrounds. Curcumin (CUR) is a low-molecular-weight polyphenolic substance obtained from the tuber part of Curcuma species. Anti-inflammatory and anti-hepatitis C virus (HCV) activities have been associated with CUR. However, its poor aqueous solubility and low systemic bioavailability have been the challenges in improving the therapeutic efficacy of curcumin. Aim. The study aimed to produce CUR-loaded liposomal solid gels as anti-HCV delivery systems. Parameters including the physical characteristics and the cell cytotoxicity properties were evaluated. Methods. The freeze-drying technique was applied to manufacture the CUR-loaded liposomal solid gels. Scanning electron microscopy (SEM), X-ray diffractometry (XRD), and differential thermal analysis (DTA) were involved to reveal the characteristics of the solid gels. Such characteristics were as follows: the morphology and the microscopic structure of the solid gels, the crystallinity structure of the curcumin, and the thermal properties of the mixtures. Furthermore, their cell cytotoxicity was investigated using a Huh7it cell line. Results. The SEM images confirmed that curcumin liposomes were intact and trapped in the solid gel matrix. The XRD data showed flat patterns diffractograms of the formulations, confirming the transformation of CUR from crystalline to amorphous form. The DTA thermograms showed a single melting endothermic peak at a higher temperature around 200°C, indicating a single-phase transition of the mixtures. The XRD and DTA data revealed the molecular dispersion of CUR in the developed formulations. The cytotoxicity data provided as cell cytotoxicity 50 (CC50) for all formulations were ≥25 mg. These data confirmed that the developed liposomal solid gels were not cytotoxic to Huh7it cell line, indicating that the anti-HCV activity would be through a specific pathway and not by its toxicity. Conclusion. The CUR-loaded liposomal solid gels exhibited the potential and offered an alternative dosage form to improve the therapeutic efficacy of curcumin as an anti-HCV....
Glutathione (GSH) is an anti-inflammatory and antioxidant biomolecule. Polycaprolactone (PCL) nanofiber mesh (NFM) is capable of the attachment and release of biomolecules for prolonged periods and has the potential as a transdermal drug delivery system during wound healing for a diabetic patient. Our earlier study found that high levels of sugar in diabetic male mice were significantly decreased by daily doses of glutathione administered on the mice. Furthermore, oxidative stress found in diabetic male mice led to the total depletion of glutathione levels in the body’s organs (pancreas, spleen, epididymis, and testis). The objective of this study was to attach GSH with PCL NFM for the controlled release of GSH biomolecules for long periods of time from the fiber mesh into a diabetic body. This study produced PCL NFM using an electrospun technique and tested it on mice to evaluate its efficiency as a dermal drug delivery mechanism. This study dissolved GSH (2.5 mg/mL) with phosphate-buffered saline (PBS) and glutaraldehyde (GLU) solution to create GSH-PBS and GSH-GLU complexes. Each complex was used to soak PCL NFM for 24 h and dried to create PCL-GSH-PBS and PCL-GSH-GLU meshes. Fiber morphology, degradation, fibroblast cell proliferation, cytotoxicity, and GSH release activities from each mesh were compared. Fibroblast cell adhesion and cytotoxicity tests found excellent biocompatibility of both GSH-immobilized PCL meshes and no degradation until 20 days of the study period. The disk diffusion method was conducted to test the antibacterial properties of the sample groups. Release tests confirmed that the attachment of GSH with PCL by GSH-GLU complex resulted in a steady release of GSH compared to the fast release of GSH from PCL-GSH-PBS mesh. The disk diffusion test confirmed that PCL-GSHGLU has antibacterial properties. The above results conclude that GSH-GLU immobilized PCL NFM can be a suitable candidate for a transdermal anti-oxidative and anti-bacterial drug delivery system such as bandage, skin graft for wound healing application in a diabetic patient....
Linezolid is an efficacious medication for the treatment of drug-resistant tuberculosis but has been associated with serious safety issues that can result in treatment interruption. The objectives of this study were thus to build a population pharmacokinetic model and to use the developed model to establish a model-informed precision dosing (MIPD) algorithm enabling safe and efficacious dosing in patients with multidrug- and extensively drug-resistant tuberculosis. Routine hospital therapeutic drug monitoring data, collected from 70 tuberculosis patients receiving linezolid, was used for model development. Efficacy and safety targets for MIPD were the ratio of unbound area under the concentration versus time curve between 0 and 24 h over minimal inhibitory concentration (fAUC0–24h/MIC) above 119 and unbound plasma trough concentration (fCmin) below 1.38 mg/L, respectively. Model building was performed in NONMEM 7.4.3. The final population pharmacokinetic model consisted of a one-compartment model with transit absorption and concentration- and time-dependent auto-inhibition of elimination. A flat dose of 600 mg once daily was appropriate in 67.2% of the simulated patients from an efficacy and safety perspective. Using the here developed MIPD algorithm, the proportion of patients reaching the efficacy and safety target increased to 81.5% and 88.2% using information from two and three pharmacokinetic sampling occasions, respectively. This work proposes an MIPD approach for linezolid and suggests using three sampling occasions to derive an individualized dose that results in adequate efficacy and fewer safety concerns compared to flat dosing....
The dosage regimen of vancomycin, teicoplanin and daptomycin remains controversial for critically ill patients undergoing continuous renal replacement therapy (CRRT). Monte Carlo simulation was applied to identify the optimal regimens of antimicrobial agents in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections based on the mechanisms of different CRRT modalities on drug clearance. The optimal vancomycin dosage for patients received a CRRT doses ≤ 30 mL/kg/h was 20 mg/kg loading dose followed by 500 mg every 8 h, while 1 g every 12 h was appropriate when 35 mL/kg/h was prescribed. The optimal teicoplanin dosage under a CRRT dose ≤ 25 mL/kg/h was four loading doses of 10 mg/kg every 12 h followed by 10 mg/kg every 48 h, 8 mg/kg every 24 h and 6 mg/kg every 24 h for continuous veno-venous hemofiltration, continuous veno-venous hemodialysis and continuous veno-venous hemodiafiltration, respectively. When the CRRT dose increased to 30–35 mL/kg/h, the teicoplanin dosage should be increased by 30%. The recommended regimen for daptomycin was 6–8 mg/kg every 24 h under a CRRT dose ≤ 25 mL/kg/h, while 8–10 mg/kg every 24 h was optimal under 30–35 mg/kg/h. The CRRT dose has an impact on probability of target attainment and CRRT modality only influences teicoplanin....
The goal of this research was to study the potential of polyelectrolyte multilayers as buccal dosage forms for drug delivery and to investigate how the properties of the drugs impact the overall performance of the delivery system. Multilayer films based on the polyelectrolyte interaction between casein and chitosan were developed using benzydamine, tolfenamic acid and betahistine as model drugs. The samples were characterized for surface pH, moisture content and moisture absorption, swelling behavior and mucoadhesion. Additionally, surface morphology was investigated, as well as the drugs’ physical state after incorporation in the multilayer films. The samples proved to be nonirritant (pH was within the physiological range), physically stable (moisture content and moisture absorption below 5%) and mucoadhesive, adsorbing from 60 to 70% mucin. The release behavior corelated to the swelling index profiles of the samples and was strongly dependent on the drug solubility. The developed multilayer films appeared to be an optimum delivery system for sparingly soluble drugs due to the high drug loading achieved....
Loading....