We report the observation of visible-light emission at room temperature from high fluence (0.3–3×1017 cm−2) Si+ implanted thermal SiO2 layers grown on silicon substrates. Significant blue-light emission and an intense broad luminescent band with a peak beyond 750 nm are observed after annealing at high temperature (T≥1000 °C). The red-light emission, present only in the highest fluence implant, is attributed to the luminescence emitted from silicon nanocrystals produced by silicon precipitation. The presence of silicon nanocrystals is confirmed by transmission electron microscopy. Significant blue-light emission is visible after thermal annealing in the 1×1017 cm−2 fluence implant. The peak position shifts from 490 to 540 nm by increasing the annealing cycles temperature.
Oxidative stress and abnormally high levels of reactive oxygen species (ROS) play an essential role in the pathogenesis and progression of inflammatory bowel disease (IBD). Oxidation‐responsive nanoparticles (NPs) are formulated from a phenylboronic esters‐modified dextran (OxiDEX) that degrades selectively in response to hydrogen peroxide (H2O2). OxiDEX NPs are coated with chitosan and encapsulated in a pH‐sensitive polymer to produce nano‐in‐micro composites. The microparticles are spherical with homogeneous particle size (53 ± 3 µm) and maintain integrity at acidic pH, preventing the premature release of the NPs in gastric conditions. The degradation of NPs is highly responsive to the level of H2O2, and the release of the drug is sustained in the presence of physiologically relevant H2O2 concentrations. The presence of chitosan on the particles surface significantly enhances NPs stability in intestinal pH and their adhesion on the intestinal mucosa. Compared to a traditional enteric formulation, this formulation shows tenfold decreased drug permeability across C2BBe1/HT29‐MTX cell monolayer, implying that lower amount of drug would be absorbed to the blood stream and, therefore, limiting the undesired systemic side effects. Based on these results, a successful nano‐in‐micro composite for targeted therapy of IBD is obtained by combination of the responsiveness to pH and ROS.
The pharmacological therapy for gastrointestinal (GI) diseases, such as inflammatory bowel diseases, continues to present challenges in targeting efficacy. The need for maximal local drug exposure at the inflamed regions of the GI tract has led research to focus on a disease-targeted drug delivery approach. Smart nanomaterials responsive to the reactive oxygen species (ROS) concentrated in the inflamed areas, can be formulated into nanoplatforms to selectively release the active compounds, avoiding unspecific drug delivery to healthy tissues and limiting systemic absorption. Recent developments of ROS-responsive nanoplatforms include combination with other materials to obtain multi-responsive systems and modifications/derivatization to increase the interactions with biological tissues, cell uptake and targeting. This review describes the applications of ROS-responsive nanosystems for on-demand drug delivery to the GI tract.
K E Y W O R D Sgastrointestinal tract drug delivery, irritable bowel disease, oxidation-responsive materials, stimuli-responsive nanocarriers
Spray congealing is a low cost, simple and versatile method to produce microparticles without the use of organic or aqueous solvent. This review provides a detailed picture of the pharmaceutical applications of this technology, with an overview of the spray-congealed-based drug-delivery systems. First, the basic principles and equipment of spray congealing technology are presented. Then, representative examples of the drug-delivery systems are examined and critically discussed. Emphasis is given on the role of formulation variables, together with practical considerations for formulation design. In addition, the current status of the industrial applications of this technology within the pharmaceutical field is examined. The final part points out benefits, limitations and future perspectives of this technology in drug delivery.
Despite the growing interest in lipid-based formulations, their polymorphism is still a challenge in the pharmaceutical industry. Understanding and controlling the polymorphic behavior of lipids is a key element for achieving the quality and preventing stability issues. This study aims to evaluate the impact of different oral-approved liquid lipids (LL) on the polymorphism, phase transitions and structure of solid lipid-based formulations and explore their influence on drug release. The LL investigated were isopropyl myristate, ethyl oleate, oleic acid, medium chain trigycerides, vitamin E acetate, glyceryl monooleate, lecithin and sorbitane monooleate. Spray-congealing was selected as an example of a melting-based solvent-free manufacturing method to produce microparticles (MPs) of tristearin (Dynasan®118). During the production process, tristearin MPs crystallized in the metastable α-form. Stability studied evidenced a slow phase transition to the stable β-polymorph overtime, with the presence of the α-form still detected after 60 days of storage at 25 °C. The addition of 10% w/w of LL promoted the transition of tristearin from the α-form to the stable β-form with a kinetic varying from few minutes to days, depending on the specific LL. The combination of various techniques (DSC, X-ray diffraction analysis, Hot-stage polarized light microscopy, SEM) showed that the addition of LL significantly modified the crystal structure of tristearin-based formulations at different length scales. Both the polymorphic form and the LL addition had a strong influence on the release behavior of a model hydrophilic drug (caffeine). Overall, the addition of LL can be considered an interesting approach to control triglyceride crystallization in the β-form. From the industrial viewpoint, this approach might be advantageous as any polymorphic change will be complete before storage, hence enabling the production of stable lipid formulations.
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