1. In Vitro Characterization of Inhalable Cationic Hybrid Nanoparticles as Potential Vaccine Carriers
Hesham M Tawfeek, Imran Y Saleem, Nitesh K Kunda, Iman M Alfagih, Kan Kaneko, Sarah R Dennison, Fars Alanazi Pharmaceuticals (Basel) . 2021 Feb 18;14(2):164. doi: 10.3390/ph14020164.
In this study, PGA-co-PDL nanoparticles (NPs) encapsulating model antigen, bovine serum albumin (BSA), were prepared via double emulsion solvent evaporation. In addition, chitosan hydrochloride (CHL) was incorporated into the external phase of the emulsion solvent method, which resulted in surface adsorption onto the NPs to form hybrid cationic CHL NPs. The BSA encapsulated CHL NPs were encompassed into nanocomposite microcarriers (NCMPs) composed of l-leucine to produce CHL NPs/NCMPs via spray drying. The CHL NPs/NCMPs were investigated for in vitro aerosolization, release study, cell viability and uptake, and stability of protein structure. Hybrid cationic CHL NPs (CHL: 10 mg/mL) of particle size (480.2 ± 32.2 nm), charge (+14.2 ± 0.72 mV), and BSA loading (7.28 ± 1.3 µg/mg) were produced. The adsorption pattern was determined to follow the Freundlich model. Aerosolization of CHL NPs/NCMPs indicated fine particle fraction (FPF: 46.79 ± 11.21%) and mass median aerodynamic diameter (MMAD: 1.49 ± 0.29 µm). The BSA α-helical structure was maintained, after release from the CHL NPs/NCMPs, as indicated by circular dichroism. Furthermore, dendritic cells (DCs) and A549 cells showed good viability (≥70% at 2.5 mg/mL after 4-24 h exposure, respectively). Confocal microscopy and flow cytometry data showed hybrid cationic CHL NPs were successfully taken up by DCs within 1 h of incubation. The upregulation of CD40, CD86, and MHC-II cell surface markers indicated that the DCs were successfully activated by the hybrid cationic CHL NPs. These results suggest that the CHL NPs/NCMPs technology platform could potentially be used for the delivery of proteins to the lungs for immunostimulatory applications such as vaccines.
2. The effect of ethanol on the habit and in vitro aerodynamic results of dry powder inhalation formulations containing ciprofloxacin hydrochloride
Piroska Szabó-Révész, Eva Roblegg, Edit Benke, Christina Winter, Rita Ambrus Asian J Pharm Sci . 2021 Jul;16(4):471-482. doi: 10.1016/j.ajps.2021.04.003.
In the case of dry powder inhalation systems (DPIs), the development of carrier-free formulations has gained increased attention. Thereby, spray-drying is a promising technology and is widely used to produce carrier-free DPIs. Numerous works have been published about the co-spray-drying of active ingredients with various solid excipients and their effect on the physicochemical characteristics and aerodynamic properties of the formulations. However, only a few studies have been reported about the role of the solvents used in the stock solutions of spray-dried formulations. In the present work, DPI microcomposites containing ciprofloxacin hydrochloride were prepared by spray-drying in the presence of different ethanol concentrations. The work expresses the roughness, depth and width of the dimples for particle size as a novel calculation possibility, and as a correlation between the MMAD/D0.5ratio and correlating it with cohesion work, these new terms and correlations have not been published - to the best of our knowledge - which has resulted in gap-filling findings. As a result, different proportions of solvent mixtures could be interpreted and placed in a new perspective, in which the influence of different concentrations of ethanol on the habit of the DPI formulations, and thus onin vitroaerodynamic results. Based on these, it became clear why we obtained the bestin vitroaerodynamic results for DPI formulation containing 30% ethanol in the stock solution.
3. Dry powder aerosols to co-deliver antibiotics and nutrient dispersion compounds for enhanced bacterial biofilm eradication
S Gharse, S Sommerfeld Ross, L Sanchez, J Fiegel Int J Pharm . 2017 Oct 5;531(1):14-23. doi: 10.1016/j.ijpharm.2017.08.060.
The purpose of this study was to formulate a dry powder for inhalation containing a combination treatment for eradication of Pseudomonas aeruginosa bacterial biofilms. Dry powders containing an antibiotic (ciprofloxacin hydrochloride, CH) and nutrient dispersion compound (glutamic acid, GA) at a ratio determined to eliminate the biofilms were generated by spray drying. Leucine was added to the spray dried formulation to aid powder flowability. A central composite design of experiments was performed to determine the effects of solution and processing parameters on powder yield and aerodynamic properties. Combinations of CH and GA eradicated bacterial biofilms at lower antibiotic concentrations compared to CH alone. Spray dried powders were produced with yields up to 43% and mass mean aerodynamic diameters (MMAD) in the respirable range. Powder yield was primarily affected by variables that determine cyclone efficiency, i.e. atomizer and solution flow rates and solution concentration; while MMAD was mainly determined by solution concentration. Fine particle fractions (FPF)<4.46μm and <2.82μm of the powders ranged from 56 to 70% and 35 to 46%, respectively. This study demonstrates that dry powder aerosols containing high concentrations of a combination treatment effective against P. aeruginosa biofilms could be developed with high yield, aerodynamic properties appropriate for inhalation, and no loss of potency.
