Burn wound infections with multidrug-resistant (MDR) bacteria are shown in many countries as severe widespread health threats. Consequently, attention has been devoted to new nanoparticle-based materials in the field of antimicrobial chemotherapy for burn wound infections. This study aimed to evaluate both in vitro and in vivo efficacies of nanoparticle–antibiotic combinations as new classes of materials subjected against MDR Pseudomonas aeruginosa. Out of 40 Gram-negative isolates, 23 P. aeruginosa were recovered from patients with burn wound infections attending different hospitals in Tanta, Egypt. The susceptibility test revealed that 95.7% of P. aeruginosa isolates were MDR with a high incidence of resistance against carbenicillin. Antibacterial activities of silver nanoparticles (Ag-NPs) against the isolates examined showed various inhibition zone diameters ranging from 11 to 17 mm. Strong synergistic efficacy of neomycin was reported in combination with Ag-NPs against MDR P. aeruginosa P8 and P14 isolates. The in vivo effectiveness of various pharmaceutical formulations prepared from a combination of neomycin antibiotic with Ag-NPs in the treatment of induced bacterially infected mice burns showed that maximum healing activity along with faster wound contraction reported with the combination of neomycin-Ag-NPs in the spray formulation. Generally, data indicated that incorporating Ag-NPs in combination with certain antibiotics may be a new, promising application for wound treatments, especially burns infected with MDR P. aeruginosa.

Objectives The aim of this research was to assess regional difference in the intestinal absorption of ranitidine HCl as an indicator for the potential effect of P‐glycoprotein (P‐gp) efflux transporters. Methods In situ rabbit intestinal perfusion was used to investigate absorption of ranitidine HCl, a substrate for P‐gp efflux from duodenum, jejunum, ileum and colon. This was conducted both in the presence and absence of piperine as P‐gp inhibitor. Key findings Ranitidine HCl was incompletely absorbed from rabbit intestine. The length normalized absorptive clearance (PeA/L) of ranitidine HCl was ranked as colon > duodenum > jejunum > ileum. This is the reverse order of the magnitude of P‐gp expression. Coperfusion of piperine with ranitidine HCl significantly increased the PeA/L of ranitidine HCl from jejunum and ileum with no significant change on the absorption from duodenum and colon. This was confirmed by significant reduction in the length required for complete ranitidine HCl absorption from jejunum and ileum in presence piperine. Conclusions The results indicate that P‐gp transporters play a major role in determining regional difference in intestinal absorption of ranitidine HCl. Thus, the regional absorption of drugs may be taken as an indirect indication for the role of P‐gp in intestinal absorption.

Dissolution enhancement is a promising strategy for improving drug bioavailability. Co-crystallization of drugs with inert material can help in this direction. The benefit will become even greater if the inert material can form co-crystal while maintaining its main function as excipient. Accordingly, the objective of the current study was to investigate xylitol as a potential co-crystal co-former for felodipine with the goal of preparing felodipine sublingual tablets. Co-crystallization was achieved by wet co-grinding of the crystals deposited from methanolic solutions containing felodipine with increasing molar ratios of xylitol (1:1, 1:2 and 1:3). The developed co-crystals were characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) before monitoring drug dissolution. These results reflected the development of new crystalline species depending on the relative proportions of felodipine and xylitol with complete co-crystallization of felodipine being achieved in the presence of double its molar concentration of xylitol. This co-crystal formulation was compressed into sublingual tablet with ultrashort disintegration time with subsequent fast dissolution. Co-crystal formation was associated with enhanced dissolution with the optimum formulation producing the fastest dissolution rate. In conclusion, xylitol can be considered as a co-crystal co-former for enhanced dissolution rate of drugs.

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The fluidity of vesicular membrane affects vesicular transdermal drug delivery. Essential oils can be located in vesicular membrane imparting flexibility and influencing transdermal delivery. Accordingly, the objective was to investigate the effect of incorporation of essential oils in niosomes on felodipine transdermal delivery. Rigid niosomes comprising Span 60 with cholesterol (2:1, w/w) were used with clove, eucalyptus or lemon oils being incorporated in the vesicles at increasing concentrations. The vesicle size and shape was monitored using scanning electron microscopy. Thermal analysis was used to monitor the thermal behavior. Drug entrapment efficiency, release and skin permeation were monitored. Niosomes were spherical with size ranging from 279 to 345 nm. The drug entrapment ranged from 97.9 to 98.8%. Thermal analysis confirmed the existence of oils within vesicular membrane and highlighted the membrane fluidizing effect. Drug release depended on the oil with clove oil or eucalyptus oil showing a trend of increased drug release compared with plain niosomes. In contrast, lemon oil reduced drug release rate. Skin permeation study reflected the superiority of oil containing niosomes. The results correlated with the fluidizing and penetration enhancing effects of oils. The study introduced essential oils as potential niosomes fluidizing agents for enhanced transdermal drug delivery.

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