The aim of this study was to prepare spray dried inhalable powders containing isoniazid-loaded chitosan/tripolyphosphate (TPP) nanoparticles for sustained delivery of the drug to the lung. Nanoparticles were prepared by ionic gelation method. In-vitro drug release study indicated that the rate of drug release from nanoparticles was decreased by increasing the amount of chitosan. Entrapment of isoniazid into chitosan/TPP nanoparticles decreased minimum inhibitory concentrations (MIC) of the drug against mycobacterium avium intracellulare. Nanoparticles were spray dried using excipients such as lactose, mannitol and maltodextrin alone or with leucine. Results showed that the obtained powders had different aerosolization property. It was observed that by adding leucine, the particle size of microparticles deceased and the process yield and fine particle fraction (FPF) increased significantly. The in-vitro deposition data indicated that spray drying of isoniazid-loaded nanoparticles with lactose in the presence of leucine resulted in the production of inhalable powders with the highest FPF (45%).

In order to develop a niosome-encapsulated ciprofloxacin (CPFX) HCl formulation for pulmonary delivery, the feasibility of encapsulation of CPFX in niosomes, its stability and nebulization capability was evaluated. Various combinations of nonionic surfactants with cholesterol were used to prepare the formulations. The in vitro deposition data of the niosomal formulations were examined using an Andersen cascade impactor. Formulations composed of Span 60 and Tween 60 in combination with 40 mol% of cholesterol exhibited high encapsulation efficacy and stability and also had fine particle fraction and nebulization efficiency of about 61.9% ± 1.0 and 77.9 ± 2.8, respectively. Minimal inhibitory concentration of the niosomal CPFX against some pulmonary pathogens were lower than free CPFX. Using the MTT assay in human lung carcinoma cell line (A549), niosome-entrapped CPFX showed significantly lower cytotoxicity in comparison to the free drug. These results indicate that niosome can be used as a carrier for pulmonary delivery of CPFX via nebulization.

Silver has been used as an antimicrobial agent for a long time in different forms, but silver nanoparticles (nanosilver) have recently been recognized as potent antimicrobial agents. Although nanosilver is finding diverse medical applications such as silver-based dressings and silver-coated medical devices, its dermal and systemic toxicity via dermal use has not yet been identified. In this study, we analyzed the potential toxicity of colloidal nanosilver in acute and subchronic guinea pigs. Before toxicity assessments, the size of colloidal nanosilver was recorded in sizes <100 nm by X-ray diffraction and transmission electron microscopy. For toxicological assessments, male guinea pigs weighing 350 to 400 g were exposed to two different concentrations of nanosilver (1000 and 10,000 µg/mL) in an acute study and three concentrations of nanosilver (100, 1000, and 10,000 µg/mL) in a subchronic study. Toxic responses were assessed by clinical and histopathologic parameters. In all experimental animals the sites of exposure were scored for any type of dermal toxicity and compared with negative control and positive control groups. In autopsy studies during the acute test, no significant changes in organ weight or major macroscopic changes were detected, but dose-dependent histopathologic abnormalities were seen in skin, liver, and spleen of all test groups. In addition, experimental animals subjected to subchronic tests showed greater tissue abnormalities than the subjects of acute tests. It seems that colloidal nanosilver has the potential to provide target organ toxicities in a dose- and time-dependent manner.