Microstructural alterations in the onychomycotic and psoriatic nail: relevance in drug delivery.

Despite the important nail alterations caused by onychomycosis and psoriasis few studies have characterized the microstructure of the diseased nail plate and the diffusion and penetration of drugs through this altered structure. This work aimed to characterize the microstructure of the healthy, onychomycotic and psoriatic human nail using Raman spectroscopy, scanning electron microscopy, optical microscope profilometry and mercury intrusion porosimetry followed by analysis of the structure with PoreCor® software. The results showed that onychomycotic nails have higher porosity and lower amounts of disulphide bonds compared to healthy nails. This suggests that the presence and action of fungi on the nail plate makes this structure more permeable to water and drugs. Psoriatic nails had increased porosity compared to healthy nails but lower than fungal infected specimens. In vitro permeation studies showed that diseased nails were more permeable to ciclopirox (onychomycosis) and clobetasol (psoriasis) although drug permeation was highly variable and likely to be influenced by the degree of alteration of the nail structure. On the whole, this work provides new and valuable information about the microstructure and porosity of diseased nails and a plausible explanation of the increased drug permeability observed in this work and elsewhere.</p

3D printed tacrolimus suppositories for the treatment of ulcerative colitis

Ulcerative colitis is a global health problem, affecting millions of individuals worldwide. As an inflammatory condition localised in the large intestine, rectal delivery of immunosuppressive therapies such as tacrolimus is a promising strategy to maximise drug concentration at the site of action whilst minimising systemic side effects. Here, for the first time, self-supporting 3D-printed tacrolimus suppositories were prepared without the aid of moulds using a pharmaceutical semi-solid extrusion (SSE) 3D printer. The suppositories were printed vertically in three different sizes using combinations of two lipid pharmaceutical excipients (Gelucire 44/14 or Gelucire 48/16) and coconut oil. Although both suppository formulations had the appropriate viscosity characteristics for printing, the Gel 44 formulation required less energy and force for extrusion compared to the Gel 48 system. The Gel 44 disintegrated more rapidly but released tacrolimus more slowly than the Gel 48 suppositories. Although the tacrolimus release profiles were significantly different, both suppository systems released more than 80% drug within 120 min. DSC and XRD analysis was inconclusive in determining the solid-state properties of the drug in the suppositories. In summary, this article reports on the fabrication of 3D printed self-supporting suppositories to deliver personalised doses of a narrow therapeutic index drug, with potential benefits for patients with ulcerative colitis

3D Printed Tacrolimus Rectal Formulations Ameliorate Colitis in an Experimental Animal Model of Inflammatory Bowel Disease

The aim of this study was to fabricate novel self-supporting tacrolimus suppositories using semisolid extrusion 3-dimensional printing (3DP) and to investigate their efficacy in an experimental model of inflammatory bowel disease. Blends of Gelucire 44/14 and coconut oil were employed as lipid excipients to obtain suppository formulations with self-emulsifying properties, which were then tested in a TNBS (2,4,6-trinitrobenzenesulfonic acid) induced rat colitis model. Disease activity was monitored using PET/CT medical imaging; maximum standardized uptake values (SUVmax), a measure of tissue radiotracer accumulation rate, together with body weight changes and histological assessments, were used as inflammatory indices to monitor treatment efficacy. Following tacrolimus treatment, a significant reduction in SUVmax was observed on days 7 and 10 in the rat colon sections compared to non-treated animals. Histological analysis using Nancy index confirmed disease remission. Moreover, statistical analysis showed a positive correlation (R2 = 71.48%) between SUVmax values and weight changes over time. Overall, this study demonstrates the effectiveness of 3D printed tacrolimus suppositories to ameliorate colitis and highlights the utility of non-invasive PET/CT imaging to evaluate new therapies in the preclinical area

Extrusion-Spheronization of Talc using Microcrystalline Cellulose as a Pellet Aid: Part I

NoThe aims of the present work were to pelletize talc by extrusion-spheronization technique using microcrystalline cellulose (MCC) as a pelletization aid and to study its performance as a neutral substrate for coating. A 32 factorial design was used to study the effect of independent variables (X1, amount of talc, and X2, MCC) on pellet properties

Incorporation of Fe@Au nanoparticles into multiresponsive pNIPAM-AAc colloidal gels modulates drug uptake and release

Here, a synthetic method has been optimized for the synthesis of thermoresponsive and pH-responsive poly(N-isopropylacrylamide-co-acrylic acid) nanogels which are subsequently loaded with cytochrome C by using a modified breathing-in mechanism. Physico-chemical properties mapped by using dynamic light scattering (DLS) and differential scanning calorimetry (DSC) confirm the swelling/deswelling kinetics as reversible with a volume phase transition temperature (VPTT) of ~39 °C. Fe@Au nanoparticles were incorporated inside the nanogel networks by using two different methods: coating and in situ growth. The latter bears closer resemblance to the nanogels only, while the former follows the trend of bare Fe@Au nanoparticles. High loading (~96 %) and encapsulation (500 μg/mg of nanogels) of cytochrome C were obtained. Release experiments performed by using a dialysis set-up and monitored by using UV-vis spectroscopy show the highest release at 40 °C and pH 3.2 (high temperature, low pH), with maximum release from the Fe@Au-coated nanogels that also show a reverse swelling-collapse trend. The location of the drug, the incorporation and presence of Fe@Au nanoparticles and the drug incorporation method are found to control both the drug release mechanism and kinetics.Incorporation of Fe@Au nanoparticles into multiresponsive pNIPAM-AAc colloidal gels modulates drug uptake and releaseacceptedVersio