Abstract Background Cystic fibrosis (CF) is a life-threatening multiorgan genetic disease, particularly affecting the lungs, where recurrent infections are the main cause of reduced life expectancy. In CF, mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein impair transepithelial electrolyte and water transport, resulting in airway dehydration, and a thickening of the mucus associated with abnormal viscoelastic properties. Our aim was to develop a rheological method to assess the effects of hypertonic saline (NaCl) and NaHCO 3 on CF sputum viscoelasticity in vitro, and to identify the critical steps in sample preparation and in the rheological measurements. Methods Sputum samples were mixed with hypertonic salt solutions in vitro in a ratio of either 10:4 or 10:1. Distilled water was applied as a reference treatment. The rheological properties of sputum from CF patients, and the effects of these in vitro treatments, were studied with a rheometer at constant frequency and strain, followed by frequency sweep tests, where storage modulus (G′), loss modulus (G″) and loss factor were determined. Results We identified three distinct categories of sputum: (i) highly elastic (G′ > 100,000 Pa), (ii) elastic (100,000 Pa > G′ > 1000 Pa), and (iii) viscoelastic (G′ < 1000). At the higher additive ratio (10:4), all of the added solutions were found to significantly reduce the gel strength of the sputum, but the most pronounced changes were observed with NaHCO 3 (p < 0.001). Samples with high elasticity exhibited the greatest changes while, for less elastic samples, a weakening of the gel structure was observed when they were treated with water or NaHCO 3 , but not with NaCl. For the viscoelastic samples, the additives did not cause significant changes in the parameters. When the lower additive ratio (10:1) was used, the mean values of the rheological parameters usually decreased, but the changes were not statistically significant. Conclusion Based on the rheological properties of the initial sputum samples, we can predict with some confidence the treatment efficacy of each of the alternative additives. The marked differences between the three categories suggest that it is advisable to evaluate each sample individually using a rheological approach such as that described here.
Semisolid dosage forms are recommended for the dermal care of babies and children. If we look at the ingredients of these preparations, there are still many cases in which there are substances (occlusive agents, preservatives) that no longer meet certain requirements of the modern age, so it is timely to replace them with other substances. The aim of this work was to formulate a science-based formulation with new components that keep or improve its moisturizing properties, rheological parameters, and microbiological stability. Occlusive oils, like white petrolatum and liquid paraffin and the preservative parabens are traditional ingredients in oil in water creams, were replaced with white beeswax, sunflower oil, and phenoxyethanol, respectively. Cocoa butter, urea, and glycerol were added to improve long-lasting hydration and support the barrier function of the reformulated creams. The rheological properties of the formulations were determined. The effects of the preparations on skin hydration and on the barrier function of the skin were tested. Furthermore, microbiological stability was investigated. The result of the reformulation was an o/w cream that provided a good longer-lasting hydration effect; supported the barrier function of the baby skin without occlusion; and had adequate consistency, easy spreading, a pleasant skin feeling, proper pH, and good microbiological stability.
Generally, topically applied eye drops have low bioavailability due to short residence time and low penetration of the drug. The aim of the present study was to incorporate dexamethasone (DXM) into nano lipid carriers (NLC), which contain mucoadhesive polymer, in order to increase the bioavailability of the drug. A 23 factorial experimental design was applied, in which the three factors were the polymer, the DXM, and the emulsifier concentrations. The samples were analyzed for particle size, zeta potential, polydispersity index, and Span value. The significant factors were identified. The biocompatibility of the formulations was evaluated with human corneal toxicity tests and immunoassay analysis. The possible increase in bioavailability was analyzed by means of mucoadhesivity, in vitro drug diffusion, and different penetration tests, such as in vitro cornea PAMPA model, human corneal cell penetration, and ex vivo porcine corneal penetration using Raman mapping. The results indicated that DXM can be incorporated in stable mucoadhesive NLC systems, which are non-toxic and do not have any harmful effect on cell junctions. Mucoadhesive NLCs can create a depot on the surface of the cornea, which can predict improved bioavailability.
Dry eye disease is a relatively common ocular problem, which causes eye discomfort and visual disorders leading to a decrease in the quality of life. The aim of this study was to find a possible excipient for eye drop formulations, which is able to stabilize the tear film. A cationic thiolated polyaspartamide polymer, poly[( N -mercaptoethylaspartamide)-co-( N -( N ′, N ′-dimethylaminoethyl)aspartamide)] (ThioPASP-DME), was used as a potential vehicle. Besides satisfying the basic requirements, the chemical structure of ThioPASP-DME is similar to those of ocular mucins as it is a protein-like polymer bearing a considerable number of thiol groups. The solution of the polymer is therefore able to mimic the physiological properties of the mucins and it can interact with the mucus layer via disulphide bond formation. The resultant mucoadhesion provides a prolonged residence time and ensures protective effect for the corneal/conjunctival epithelium. ThioPASP-DME also has an antioxidant effect due to the presence of the thiol groups. The applicability of ThioPASP-DME as a potential excipient in eye drops was determined by means of ocular compatibility tests and through examinations of the interactions with the mucosal surface. The results indicate that ThioPASP-DME can serve as a potential eye drop excipient for the therapy of dry eye disease.
Background: Periodontitis is a chronic inflammatory disease, which affects the supporting tissues of the teeth, and without proper treatment it may lead to tooth loss. Antibiotics - administered orally - have been widely used in the treatment of periodontitis. With the conventional administration routes, adequate drug levels cannot be reached in the periodontal pockets and oral application of antimicrobials could lead to side effects. Drug delivery systems containing antibiotics, administered at the site of infection, could possibly help eliminate pathogen bacteria and treat periodontitis. Objective: The aim of the recent study was to create a locally swellable, biodegradable, biocompatible, mucoadhesive, lipophilic drug delivery system containing antimicrobial drugs which softens at body temperature, accommodate to the shape of the periodontal pocket and can provide extended drug release for at least one week. Methods: During the formulation, thermoanalytical, consistency, wettability, swelling, degradation and drug release studies were applied to determine the ideal ratios of lipid bases, structure-building components and surface active agent concentrations. Results and Discussion: The structure-building component cetostearyl alcohol appeared to be the most convenient, thanks to its wettability and mechanical properties, which led to controlled drug release. With the use of ideal concentrations of components (10% surfactant, 40% structure-building component, 32 % lipid base, 15% antimicrobial agent and 3% polymer), sustained drug release can be provided up to nearly 3 weeks. Keywords: Lipid drug delivery, sustained drug release, swelling, degradation, periodontitis, periodontal pocket, antimicrobial therapy.