Chitosan cross-linked pentasodium tripolyphosphate particles were produced by ionotropic gelation. The aim of this study was to evaluate the influence of the molar mass and deacetylation degree of ...chitosan and of the concentration of pentasodium tripolyphosphate in the production of chitosan micro/nanoparticles. The obtained charge ratio (R±), mean particle size, surface electrical charge, polydispersity index, and tendency of particle aggregation were selected as dependent variables. Results demonstrated that stable particles exhibited a high zeta potential value, between +62 and +68 mV. Particles were produced in different size ranges controlling the R± between the positively charged chitosan and negatively charged pentasodium tripolyphosphate. Chitosan micro/nanoparticles were successfully prepared via the ionic gelation method controlling R±, therefore the association of an active ingredient to a micro/nanoparticle allows the molecule to intimately interact with specific structures, to overcome barriers and to prolong its residence time in the target. Chitosan cross-linked pentasodium tripolyphosphate particles are expected to be a good approach for active ingredients formulation in the agrofood sector and related industries.
The adrenal cortical carcinoma (ACC) treatment, for which mitotane (o,p′-DDD) is the drug of choice, still remains a challenge both because of the well-known solubility problems of the drug, and its ...serious side effects. Mitotane is currently administered as oral tablets. The loading of mitotane into nanocarriers has been suggested as a way to circumvent the low solubility of the drug and its limited oral bioavailability. In this work, we have developed liposomes containing mitotane to enhance its intestinal absorption and oral bioavailability. Liposomes were produced by spray-drying of a mixture of phospholipids and the developed formulation was optimized by studying the degree of crystallinity, spray-drying conditions, phospholipid/mitotane ratio, and influence of mannitol in the hydrating ethanolic solution. An optimal liposomal formulation was produced with a phospholipid:mitotane combination (3.34:1), exhibiting a mean hydrodynamic diameter around 1 μm and spherical shape. The produced mitotane liposomes were re-suspended by hydrating the spray-dried powders in a stirred tank, and tested their intestinal permeability (ex vivo) and relative bioavailability (in vivo), against a free drug solution (with or without Trigliceril
®
CM). Our results support the conclusion that the loading of mitotane in liposomes enhanced its intestinal absorption and relative bioavailability.
Polymeric nanocapsules with elastic characteristics were prepared by the pre-formed polymer interfacial deposition method. The system consists of an oily core of retinyl palmitate with Span 60 and a ...polymeric wall of poly(
d,
l-lactide) (PLA). A narrow size distribution (215
nm, P.D.I. 0.10) was showed by dynamic light scattering (DLS) analyses. Particle deformability was observed by transmission electron microscopy (TEM) images and permeation of the particles through two superposed membranes of smaller pore diameters. Permeation studies were achieved using plastic surgery abdominal human skin by Franz diffusion cell. Retinyl palmitate permeates into deep skin layers. Besides, a PLA fluorescent derivative conjugated with Nile blue dye by an amide covalent bound was additionally obtained. Permeation profile of the nanocapsules with the fluorescent polymer was evaluated by confocal laser scanning microscopy (CLSM). The CLSM showed that nanocapsules were distributed uniformly, suggesting that the permeation mechanism through skin is intercellular. Thus, the use of these nanocapsules may be a feasible strategy to enhance the permeation of actives into the skin when delivery to deep layers is aimed.
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Microbial hyaluronic acid (bio-HA) is a highly valued product due to its wide range of aesthetic and medical applications. High purity is an essential requirement for those ...applications. HA is a polyelectrolyte susceptible to structural changes with pH; therefore, precipitation with organic solvents is attractive as a downstream processing step. However, its high hydration capacity requires a low dielectric constant solvent such as isopropyl alcohol (IPA) for better performance. Although precipitation is a typical step of polymer purification, there is still a lack of data relating the changes in the colloidal domain to precipitation performance. Therefore, this work examined the changes in zeta potential (ZP) surface tension (ST) and hydrodynamic size (HS) as functions of pH before and after bio-HA precipitations with IPA from a culture medium containing soy peptone (SP) as the main contaminant. The results showed that the structural and surface changes mediated by pH as well as the proportion of IPA:broth were correlated with the recovery and purity of bio-HA. The best results for recovery (R) and purity (P) were obtained at 2:1 IPA/broth v/v with 76.0 ± 6.6% (R) and 79.0 ± 1.8% (P) at pH 3, as well as 72.0 ± 7.5% (R) and 74.0 ± 2.7% (P) at pH 7. These findings are relevant for a better understanding of the interactions at the colloidal level that lead to the optimization of the bio-HA precipitation step based on the structural and surface properties.
The effects of estrogen-containing contraceptives on disease activity in women with systemic lupus erythematosus have not been determined.
We conducted a single-blind clinical trial involving 162 ...women with systemic lupus erythematosus who were randomly assigned to combined oral contraceptives, a progestin-only pill, or a copper intrauterine device (IUD). Disease activity was assessed at 0, 1, 2, 3, 6, 9, and 12 months according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The primary outcome was global disease activity, which we estimated by measuring the area under the SLEDAI curve. Secondary outcomes included the maximum SLEDAI score, change in SLEDAI score, incidence of lupus flares, median time to first flare, systemic lupus erythematosus treatment, and adverse events. The results were analyzed by the intention-to-treat method.
At baseline, all demographic features and disease characteristics were similar in the three groups. The mean (+/-SD) SLEDAI score was 6.1+/-5.6 in the group assigned to combined oral contraceptives, 6.4+/-4.6 in the group assigned to the progestin-only pill, and 5.0+/-5.3 in the group assigned to the IUD (54 patients in each group) (P=0.36). Disease activity remained mild and stable in all groups throughout the trial. There were no significant differences among the groups during the trial in global or maximum disease activity, incidence or probability of flares, or medication use. The median time to the first flare was three months in all groups. Thromboses occurred in four patients (two in each of the two groups receiving hormones), and severe infections were more frequent in the IUD group. One patient receiving combined oral contraceptives died from amoxicillin-related severe neutropenia.
Global disease activity, maximum SLEDAI score, incidence of flares, time to first flare, and incidence of adverse events were similar among women with systemic lupus erythematosus, irrespective of the type of contraceptive they were using.
In article number 1906330, Jeroen Leijten, Su Ryon Shin, and co‐workers develop 3D cartilage‐like tissue through local bioprinting of mesenchymal stem cell spheroids laden with soft and cell ...stimulating bioink within a mechanically robust hydrogel. This uncoupling of the micro and macro mechanical properties of the 3D printed construct allows it to possess both a chondrogenic microenvironment and the ability to withstand mechanical loads.
The aim of the present work was to load mitotane, an effective drug for adrenocortical carcinoma treatment, in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). The SLN and NLC ...were successfully prepared by high shear homogenization followed by hot high pressure homogenization. Formulations were composed of cetyl palmitate as the solid lipid for SLN, whereas for NLC PEGylated stearic acid was selected as solid lipid and medium chain triacylglycerols as the liquid lipid. Tween® 80 and Span® 85 were used as surfactants for all formulations. The particle size, zeta potential, polydispersity index (PI), encapsulation efficiency (EE), and loading capacity (LC) were evaluated. The SLN showed a mean particle size of 150 nm, PI of 0.20, and surface charge −10 mV, and the EE and LC could reach up to 92.26% and 0.92%, respectively. The NLC were obtained with a mean particle size of 250 nm, PI of 0.30, zeta potential −15 mV and 84.50% EE, and 0.84% LC, respectively. Hydrophilic coating of SLN with chitosan or benzalkonium chloride was effective in changing zeta potential from negative to positive values. The results suggest that mitotane was efficiently loaded in SLN and in NLC, being potential delivery systems for improving mitotane LC and controlled drug release.
This study focuses on the physicochemical characterization of lipid materials useful for the production of the so-called solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). The ...chosen lipids were Dynasan
®
114 (glyceril trimyristate) and Dynasan
®
118 (glyceril tristearate) as solid lipids (SL), melting temperature above 80 °C, and Miglyol
®
812 (caprylic/capric triglyceride) and Miglyol
®
840 (propylene glycol dicaprylate/dicaprate) as liquid lipids (LL), crystallizing below −15 °C. Raw lipids (pure or SL:LL mixtures) were analyzed by differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD), and Polarized Light Microscopy (PLM), before and after tempering at 80 °C for 1 h. The selected SL:LL combination was 70% (Dynasan
®
114 and 118) and 30% (Miglyol
®
812 and 840) for the production of SLN and NLC by high-pressure homogenization (HPH), respectively. Particles with a mean size of 200 nm (polydispersity index <0.329) and zeta potential of −15 mV were obtained, and their long-term stability was confirmed for 3 months of storage at 7 °C.
Polyvinyl alcohol (PVA) hydrogels both pure and reinforced with two types of carbon nanoparticles (nanotubes and nanofibres) were studied as a candidate material for osteochondral defect repair. The ...carbon nanoparticles produced by chemical vapour deposition were characterised by Raman spectroscopy, field emission scanning electron microscopy and high-resolution transmission electron microscopy. The hydrogels were surgically implanted in osteochondral defects in the articular cartilage of rats and, after 3 and 12weeks of follow-up, examined by scanning electron microscopy (SEM), optical microscopy (OM), creep indentation test (CIT) and X-ray fluorescence (XRF). No sign of tissue adhesion or abrasive wear could be seen by SEM. OM revealed dense connective tissue at the interface after 3weeks and neoformed bone tissue without significant inflammatory process after 12weeks. Dense connective tissue could be seen at the pure-PVA/tissue interface after 12weeks, but not at the carbon reinforced-PVA/tissue interface after the same follow-up time. The hydrogel creep modulus increased with follow-up time. XRF revealed an increasing concentration of calcium and phosphorus in the implants over time, a phenomenon more pronounced for the hydrogels with carbon nanofibres. The results suggest that PVA hydrogel with carbon nanoparticles elicits a stronger biological response than pure hydrogel.
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