In a novel attempt, nalidixic acid was formulated in different topical 1%(w/w) gel and cream bases. The viscosity, pH and drug content of preparations were investigated. The highest in vitro release was achieved by (Na-CMC) gel base. The presence of isopropanol as a cosolvent and nalidixic acid sodium benzoate solid dispersion (1: 8) in the selected formulae had enhanced both the in vitro release and antibacterial activity of nalidixic acid. Both DSC and FTIR spectroscopy had shown that the drug is compatible with selected excepients. All cream formulations had shown weaker antibacterial activity therefore only gel bases were further investigated for their stability. No significant change in pH or drug content had been observed in stored gel formulations. The best clinical result in impetigo was achieved after 4-7 days with treatment by gel containing isopropanol and nalidixic acid sodium benzoate solid dispersion (1:8).

In a novel attempt, nalidixic acid was formulated in different topical 1%(w/w) gel and cream bases. The viscosity, pH and drug content of preparations were investigated. The highest in vitro release was achieved by (Na-CMC) gel base. The presence of isopropanol as a cosolvent and nalidixic acid sodium benzoate solid dispersion (1: 8) in the selected formulae had enhanced both the in vitro release and antibacterial activity of nalidixic acid. Both DSC and FTIR spectroscopy had shown that the drug is compatible with selected excepients. All cream formulations had shown weaker antibacterial activity therefore only gel bases were further investigated for their stability. No significant change in pH or drug content had been observed in stored gel formulations. The best clinical result in impetigo was achieved after 4-7 days with treatment by gel containing isopropanol and nalidixic acid sodium benzoate solid dispersion (1:8).

In a novel attempt, nalidixic acid was formulated in different topical 1%(w/w) gel and cream bases. The viscosity, pH and drug content of preparations were investigated. The highest in vitro release was achieved by (Na-CMC) gel base. The presence of isopropanol as a cosolvent and nalidixic acid sodium benzoate solid dispersion (1: 8) in the selected formulae had enhanced both the in vitro release and antibacterial activity of nalidixic acid. Both DSC and FTIR spectroscopy had shown that the drug is compatible with selected excepients. All cream formulations had shown weaker antibacterial activity therefore only gel bases were further investigated for their stability. No significant change in pH or drug content had been observed in stored gel formulations. The best clinical result in impetigo was achieved after 4-7 days with treatment by gel containing isopropanol and nalidixic acid sodium benzoate solid dispersion (1:8).

Objective: To enhance 5-fluorouracil (5-FU) permeability through the skin by loading onto gold nanoparticles (GNPs) capped with two cationic ligands, benzalkonium chloride (BC) or poly (ethylene imine) (PEI). Whereas 5-FU has excellent efficacy against many cancers, its poor permeability through biological membranes and several adverse effects limit its clinical benefits. BC and PEI were selected to stabilize GNPs and to load 5-FU through ionic interactions. Methods: 5-FU/BC-GNPs and 5-FU/PEI-GNPs were prepared at different 5-FU/ligand molar ratios and different pH values and were evaluated using different techniques. GNPs stability was tested as a function of salt concentration and storage time. 5-FU release from BC- and PEI-GNPs was evaluated as a function of solution pH. Ex vivo permeability studies of different 5-FU preparations were carried out using mice skin. Results: 5-FU-loaded GNPs size and surface charge were dependent on the 5-FU/ligand molar ratios. 5-FU entrapment efficiency and loading capacity were dependent on the used ligand, 5-FU/ligand molar ratio and solution pH. Maximum drug entrapment efficiency of 59.0 ± 1.7% and 46.0 ± 1.1% were obtained for 5-FU/BC-GNPs and 5-FU/PEI-GNPs, respectively. 5-FU-loaded GNPs had good stability against salinity and after storage for 4 months at room temperature and at 4°C. In vitro 5-FU release was pH- and ligand-dependent where slower release was observed at higher pH and for 5-FU/BC-GNPs. 5-FU permeability through mice skin was significantly higher for drug-loaded GNPs compared with drug-ligand complex or drug aqueous solution. Conclusion: Based on these results, BC- and PEI-GNPs might find applications as effective topical delivery systems of 5-FU.

Objective: To enhance 5-fluorouracil (5-FU) permeability through the skin by loading onto gold nanoparticles (GNPs) capped with two cationic ligands, benzalkonium chloride (BC) or poly (ethylene imine) (PEI). Whereas 5-FU has excellent efficacy against many cancers, its poor permeability through biological membranes and several adverse effects limit its clinical benefits. BC and PEI were selected to stabilize GNPs and to load 5-FU through ionic interactions. Methods: 5-FU/BC-GNPs and 5-FU/PEI-GNPs were prepared at different 5-FU/ligand molar ratios and different pH values and were evaluated using different techniques. GNPs stability was tested as a function of salt concentration and storage time. 5-FU release from BC- and PEI-GNPs was evaluated as a function of solution pH. Ex vivo permeability studies of different 5-FU preparations were carried out using mice skin. Results: 5-FU-loaded GNPs size and surface charge were dependent on the 5-FU/ligand molar ratios. 5-FU entrapment efficiency and loading capacity were dependent on the used ligand, 5-FU/ligand molar ratio and solution pH. Maximum drug entrapment efficiency of 59.0 ± 1.7% and 46.0 ± 1.1% were obtained for 5-FU/BC-GNPs and 5-FU/PEI-GNPs, respectively. 5-FU-loaded GNPs had good stability against salinity and after storage for 4 months at room temperature and at 4°C. In vitro 5-FU release was pH- and ligand-dependent where slower release was observed at higher pH and for 5-FU/BC-GNPs. 5-FU permeability through mice skin was significantly higher for drug-loaded GNPs compared with drug-ligand complex or drug aqueous solution. Conclusion: Based on these results, BC- and PEI-GNPs might find applications as effective topical delivery systems of 5-FU.

Objective: To enhance 5-fluorouracil (5-FU) permeability through the skin by loading onto gold nanoparticles (GNPs) capped with two cationic ligands, benzalkonium chloride (BC) or poly (ethylene imine) (PEI). Whereas 5-FU has excellent efficacy against many cancers, its poor permeability through biological membranes and several adverse effects limit its clinical benefits. BC and PEI were selected to stabilize GNPs and to load 5-FU through ionic interactions. Methods: 5-FU/BC-GNPs and 5-FU/PEI-GNPs were prepared at different 5-FU/ligand molar ratios and different pH values and were evaluated using different techniques. GNPs stability was tested as a function of salt concentration and storage time. 5-FU release from BC- and PEI-GNPs was evaluated as a function of solution pH. Ex vivo permeability studies of different 5-FU preparations were carried out using mice skin. Results: 5-FU-loaded GNPs size and surface charge were dependent on the 5-FU/ligand molar ratios. 5-FU entrapment efficiency and loading capacity were dependent on the used ligand, 5-FU/ligand molar ratio and solution pH. Maximum drug entrapment efficiency of 59.0 ± 1.7% and 46.0 ± 1.1% were obtained for 5-FU/BC-GNPs and 5-FU/PEI-GNPs, respectively. 5-FU-loaded GNPs had good stability against salinity and after storage for 4 months at room temperature and at 4°C. In vitro 5-FU release was pH- and ligand-dependent where slower release was observed at higher pH and for 5-FU/BC-GNPs. 5-FU permeability through mice skin was significantly higher for drug-loaded GNPs compared with drug-ligand complex or drug aqueous solution. Conclusion: Based on these results, BC- and PEI-GNPs might find applications as effective topical delivery systems of 5-FU.

An injectable hydrogel based on the inclusion complexation of polymerized β-cyclodextrin (pβ-CD) and cholesterol terminated poly(ethylene glycol) (PEG-chol) was developed and used as a delivery system for both macromolecules and small drugs. The hydrogel was characterized by different analyses including X-ray diffraction, differential scanning calorimetry and scanning electron microscopy. The effects of pβ-CD/PEG-chol ratio and PEG-chol architecture on the hydrogel properties were also investigated. Cytotoxicity of the hydrogel was evaluated in NIH 3T3 fibroblasts using MTS assay. The hydrogel had an elastic behavior even at high temperature since the gelation temperature was observed at 69 °C. Highest hydrogel strength and stability were observed for the 8-armed PEG-chol at a pβ-CD/PEG-chol ratio of 1:1, w/w. Hydrogel degradation in phosphate buffered saline occurred by gradual erosion over the course of two months. IgG, a model hydrophilic macromolecule and riluzole, a model hydrophobic small drug were incorporated into the hydrogel and quantitatively released in a sustained fashion. The released IgG maintained its bioactivity confirming the absence of deleterious effects on protein structure during loading and release. The hydrogels showed no toxicity on NIH 3T3 fibroblasts confirming their biocompatibility. These results confirm the potential of pβ-CD/PEG-chol hydrogel as a versatile delivery system for drugs of different molecular weights and nature.

Ketorolac tromethamine (KT) is considered as a member of NSAIDs that used in treatment of rheumatoid arthritis. The main problems associated with the frequent administration of KT orally could be overcome by alternative routes as topical application. KT was formulated in different topical formulations such as gels, emulgels and creams. Sodium carboxymethylcellulose, carbopol 934 and pluronic F127 were used as polymers. In vitro permeation study through rat skin was carried out. The effect of different KT concentrations and the effect of skin penetration enhancer on the amount of KT permeated were investigated. Anti-inflammatory activity using commercial piroxicam gel for comparison was evaluated. The effectiveness and tolerability of the selected KT gel and piroxicam gel in osteoarthritis patients was also studied. The results obtained showed that, the flux of the drug increased with increasing its initial concentration. Using sodium lauryl sulfate as enhancer resulted in an improvement of KT permeation through rat skin. All formulations had the potential for local applications of KT as anti-inflammatory drug as compared to the control group. There was no significant difference in the efficacy between the selected KT gel and piroxicam gel for osteoarthritis patients. So KT gel may be used as another therapeutic option for the treatment of patients with osteoarthritis.

Ketorolac tromethamine (KT) is considered as a member of NSAIDs that used in treatment of rheumatoid arthritis. The main problems associated with the frequent administration of KT orally could be overcome by alternative routes as topical application. KT was formulated in different topical formulations such as gels, emulgels and creams. Sodium carboxymethylcellulose, carbopol 934 and pluronic F127 were used as polymers. In vitro permeation study through rat skin was carried out. The effect of different KT concentrations and the effect of skin penetration enhancer on the amount of KT permeated were investigated. Anti-inflammatory activity using commercial piroxicam gel for comparison was evaluated. The effectiveness and tolerability of the selected KT gel and piroxicam gel in osteoarthritis patients was also studied. The results obtained showed that, the flux of the drug increased with increasing its initial concentration. Using sodium lauryl sulfate as enhancer resulted in an improvement of KT permeation through rat skin. All formulations had the potential for local applications of KT as anti-inflammatory drug as compared to the control group. There was no significant difference in the efficacy between the selected KT gel and piroxicam gel for osteoarthritis patients. So KT gel may be used as another therapeutic option for the treatment of patients with osteoarthritis.

Ketorolac tromethamine (KT) is considered as a member of NSAIDs that used in treatment of rheumatoid arthritis. The main problems associated with the frequent administration of KT orally could be overcome by alternative routes as topical application. KT was formulated in different topical formulations such as gels, emulgels and creams. Sodium carboxymethylcellulose, carbopol 934 and pluronic F127 were used as polymers. In vitro permeation study through rat skin was carried out. The effect of different KT concentrations and the effect of skin penetration enhancer on the amount of KT permeated were investigated. Anti-inflammatory activity using commercial piroxicam gel for comparison was evaluated. The effectiveness and tolerability of the selected KT gel and piroxicam gel in osteoarthritis patients was also studied. The results obtained showed that, the flux of the drug increased with increasing its initial concentration. Using sodium lauryl sulfate as enhancer resulted in an improvement of KT permeation through rat skin. All formulations had the potential for local applications of KT as anti-inflammatory drug as compared to the control group. There was no significant difference in the efficacy between the selected KT gel and piroxicam gel for osteoarthritis patients. So KT gel may be used as another therapeutic option for the treatment of patients with osteoarthritis.