Despite its broad-spectrum antifungal properties, voriconazole has many side effects when administered systemically. The aim of this work was to develop an ethosomal topical delivery system for voriconazole and test its potential to enhance the antifungal properties and skin delivery of the drug. Voriconazole was encapsulated into various ethosomal preparations and the effect of phospholipid and ethanol concentrations on the ethosomes properties were evaluated. The ethosomes were evaluated for drug encapsulation efficiency, particle size and morphology and antifungal efficacy. Drug permeability and deposition were tested in rat abdominal skin. Drug encapsulation efficiency of up to 46% was obtained and it increased with increasing the phospholipid concentration, whereas the opposite effect was observed for the ethanol concentration. The ethosomes had a size of 420-600 nm and negative zeta potential. The particle size of the ethosomes increased by increasing their ethanol content. The ethosomes achieved similar inhibition zones against Aspergillus flavus at a 2-fold lower drug concentration compared with drug solution in dimethyl sulfoxide. The ex vivo drug permeability through rat abdominal skin was ∼6-fold higher for the ethosomes compared with the drug hydroalcoholic solution. Similarly, the amount of drug deposited in the skin was higher for the ethosomes and was dependent on the ethanol concentration of the ethosomes. These results confirm that voriconazole ethosomal preparations are promising topical delivery systems that can enhance the drug antifungal efficacy and improve its skin delivery.

Invasive fungal infections are becoming a major health concern in several groups of patients leading to severe morbidity and mortality. Moreover, cutaneous fungal infections are a major cause of visits to outpatient dermatology clinics. Despite the availability of several effective agents in the antifungal drug arena, their therapeutic outcome is less than optimal due to limitations related to drug physicochemical properties and toxicity. For instance, poor aqueous solubility limits the formulation options and efficacy of several azole antifungal drugs while toxicity limits the benefits of many other drugs. Nanoparticles hold great promise to overcome these limitations due to their ability to enhance drug aqueous solubility, bioavailability and antifungal efficacy. Further, drug incorporation into nanoparticles could greatly reduce its toxicity. Despite these interesting nanoparticle features, there are only few marketed nanoparticle-based antifungal drug formulations. This review sheds light on different classes of nanoparticles used in antifungal drug delivery, such as lipid-based vesicles, polymeric micelles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and dendrimers with emphasis on their advantages and limitations. Translation of these nanoformulations from the lab to the clinic could be facilitated by focusing the research on overcoming problems related to nanoparticle stability, drug loading and high cost of production and standardization.

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The rationale of the present work is to formulate and evaluate metoprolol tartrate (MT), which is a beta-1 selective adrenergic blocking agent in a new ocular gel delivery system; this is our way and method to increase its contact to the cornea, giving a longer time of drug contact to the eye and slow possible release from the preparation. Metoprolol tartrate is chosen as a candidate for gel formulation because although it has been available for a few years as ophthalmic solutions, it has not been marketed as an ocular gel yet. Two polymers; Carbopol 934 and Pluronic F127 (PF127) were used in two different concentrations in this study. Metoprolol tartrate was used in two concentrations, 0.5% and 1% (w/w). All formulations were exposed to visual examinations, pH measurement, in vitro release, rheological study and differential scanning calorimetry (DSC). Results showed that all formulations were clear, showed pH within the acceptable range suitable to be administered in the eye, and exhibited pseudoplastic flow behavior. DSC results concluded that, MT was compatible with different polymers used. In vitro release results showed that the release rate of metoprolol tartrate from gel preparations decreased as an inverse function of polymer concentration, and the release rate of the drug increased as the initial concentration increased. Intra-ocular pressure (IOP) measurements of rabbit’s eye treated with 1% (w/w) metoprolol tartrate in gel formulations with different concentrations of the polymer were determined. Carbopol 934 gel formulations showed that this polymer extended the duration of pressure reducing effect of MT to more than 5hr when compared with Pluronic F127 gel formulations. The area above the curve (AAC), maximum response, time of maximum response (tmax), and the duration of the drug action were also calculated.

Because of their ability to translocate different cargos into cells, arginine-rich cell penetrating peptides (CPPs) are promising vehicles for drug and gene delivery. The use of CPP-based carriers, however, is hampered by the lack of specificity and by interactions with negative serum components. Polyethylene glycol (PEG) is used to decrease such non-specific interactions, albeit its use is associated with reduced transfection efficiency. In this study, we describe the development of PEGylated CPP-based gene carrier with an improved targeting and a high transfection activity. The system was prepared by condensing DNA with a polycation followed by coating with a lipid envelope containing the octaarginine (R8) peptide as a model CPP. R8-modified nanoparticles produced high transfection activities, but the efficiency was reduced by PEG shielding. The reduced activity could be fully restored by the addition of a targeting ligand and a pH-sensitive fusogenic peptide. The efficiency of the proposed system is quite high, even in the presence of serum, and shows improved targeting and selectivity. Surprisingly, the effect of the fusogenic peptide was dramatically reduced in the absence of R8. Although shielded, R8 augmented the activity of the fusogenic peptide, suggesting a synergistic effect between the two peptides at the intracellular level.

We report on the development of a highly efficient gene delivery system based on synergism between octaarginine (R8), a representative cell penetrating peptide, and YSK05, a recently developed pH-sensitive cationic lipid. Attaching a high density of R8 on the surface of YSK05 nanoparticles (NPs) that contained encapsulated plasmid DNA resulted in the formation of positively charged NPs with improved transfection efficiency. To avoid the development of a net positive charge, we controlled the density and topology of the R8 peptide through the use of a two-step coating methodology, in which the inner lipid coat was modified with a low density of R8 which was then covered with an outer neutral YSK05 lipid layer. Although used in low amounts, the R8 peptide improved cellular uptake and endosomal escape of the DNA encapsulated in YSK05 NPs, which resulted in a high transfection efficiency. The two-step coating design was essential for achieving a high degree of transfection, as evidenced by the low activity of NPs modified with the same amount of R8 in a regular single-coated design. In addition, a high transfection efficiency was not observed when R8 or YSK05 were used alone, which confirms the existence of a synergistic effect between both components. The results of this study indicate that cationic cell penetrating peptides have the ability to improve transfection activities without imparting a net positive charge when used in the proper amount and in conjunction with the appropriate design. This is expected to significantly increase the potential applications of these peptides as tools for augmenting the activity of lipid nanoparticles used in gene delivery.

Background: Bacterial vaginosis (BV) is one of the most common infections in childbearing age. Aim: To compare the efficacy of metronidazole (once-daily 0.8% MTZ in situ gel) versus twice-daily conventional MTZ vaginal gel in the treatment of bacterial vaginosis (BV). Material and methods: All patients who presented to Assiut Women Health Hospital- Egypt with symptoms suggestive of BV were counseled to participate in the study. One hundred-four eligible participants were randomly assigned to either MTZ in situ gel or a conventional vaginal gel. All participants were followed-up twice after one and 4 weeks of the beginning of treatment to ensure cure of infection and any side-effects. Results: Demographic criteria of the participants were matched in both groups. The cure rate after one week from the treatment was 74.5% in the in situ gel group and 63.8% in the conventional vaginal gel group (P=0.252), while after 4 weeks, the cure rate showed significant difference in the in situ gel group as compared to the conventional vaginal gel group (66.7%) and (40.4%), respectively (P=0.009). Conclusion: Once daily in situ MTZ gel (0.8%) is more effective than twice-daily conventional gel after four weeks of treatment with nearly same side effects. These findings confirm the use of this novel and efficient modality of long-term treatment of BV.

Background: Bacterial vaginosis (BV) is one of the most common infections in childbearing age. Aim: To compare the efficacy of metronidazole (once-daily 0.8% MTZ in situ gel) versus twice-daily conventional MTZ vaginal gel in the treatment of bacterial vaginosis (BV). Material and methods: All patients who presented to Assiut Women Health Hospital- Egypt with symptoms suggestive of BV were counseled to participate in the study. One hundred-four eligible participants were randomly assigned to either MTZ in situ gel or a conventional vaginal gel. All participants were followed-up twice after one and 4 weeks of the beginning of treatment to ensure cure of infection and any side-effects. Results: Demographic criteria of the participants were matched in both groups. The cure rate after one week from the treatment was 74.5% in the in situ gel group and 63.8% in the conventional vaginal gel group (P=0.252), while after 4 weeks, the cure rate showed significant difference in the in situ gel group as compared to the conventional vaginal gel group (66.7%) and (40.4%), respectively (P=0.009). Conclusion: Once daily in situ MTZ gel (0.8%) is more effective than twice-daily conventional gel after four weeks of treatment with nearly same side effects. These findings confirm the use of this novel and efficient modality of long-term treatment of BV.

Background: Bacterial vaginosis (BV) is one of the most common infections in childbearing age. Aim: To compare the efficacy of metronidazole (once-daily 0.8% MTZ in situ gel) versus twice-daily conventional MTZ vaginal gel in the treatment of bacterial vaginosis (BV). Material and methods: All patients who presented to Assiut Women Health Hospital- Egypt with symptoms suggestive of BV were counseled to participate in the study. One hundred-four eligible participants were randomly assigned to either MTZ in situ gel or a conventional vaginal gel. All participants were followed-up twice after one and 4 weeks of the beginning of treatment to ensure cure of infection and any side-effects. Results: Demographic criteria of the participants were matched in both groups. The cure rate after one week from the treatment was 74.5% in the in situ gel group and 63.8% in the conventional vaginal gel group (P=0.252), while after 4 weeks, the cure rate showed significant difference in the in situ gel group as compared to the conventional vaginal gel group (66.7%) and (40.4%), respectively (P=0.009). Conclusion: Once daily in situ MTZ gel (0.8%) is more effective than twice-daily conventional gel after four weeks of treatment with nearly same side effects. These findings confirm the use of this novel and efficient modality of long-term treatment of BV.