1,720,978 research outputs found
Evaluation of nano spray-drying as a two-step method for solid lipid nanoparticle dry powder fabrication
No full textIn this study, the nano spray-drying technique [1-3] was investigated as an innovative two-step method to produce solid lipid nanoparticles (SLN) in the form of a dry powder. Compritol was chosen as wall-forming lipid due to its biocompability and high melting point. Cetyl palmitate was also examined for comparison. The SLN were fabricated as SLN embedded leucine microparticle (SLN-LM) dry powder.
Briefly, an O/W emulsion of lipid dissolved in chloroform and a surfactant plus L-leucine aqueous solution was prepared using Ultra-Turrax. A screening on emulsification conditions was performed in order to establish optimal lipid concentration and type of surfactant. The best emulsion was obtained by using Lutrol as a surfactant and 125 mg/mL lipid concentration.
Formulation and spray-drying factor effects on the obtained particles were evaluated by a two-step experimental design approach: step 1) a 2-level fractional factorial design was employed to determine the most influential factors; step 2) the design was extended over a previously determined working space by reducing the number of factors. Compritol concentration, L-leucine/lipid ratio and Lutrol concentration resulted the most relevant factors. Spray-drying parameters were less relevant. The best features in terms of morphology, SLN fraction and size obtained from the first design were achieved using 125 mg/mL Compritol, 1.5% w/v Lutrol and 1:1 lipid/L-leucine ratio, while the spray-drying conditions were 110°C inlet temperature, 100 L/min air flow rate and 50 mbar pressure. The composite particles were regular with a mean size of 1.1 ± 0.3 μm and a SLN population around 150 nm. However, yield was as low as 10%.
In this regard, the second design step allowed to reach 51% yield, 3.2 ± 1.8 μm SLN-LM size by maintaining the same SLN population around 150 nm. Such a result was achieved by reducing Compritol concentration to 40 mg/mL and decreasing lipid/L-leucine ratio to 1:3, using 95°C inlet temperature, 100 L/min air flow rate and 40 mbar pressure. Although the obtained SLN-LM were larger and less regular, such conditions were considered an acceptable compromise between SLN size distribution, morphology and yield. Increase in Lutrol concentration or the use of cetyl palmitate worsened SLN features and particle homogeneity. An improvement in the emulsification step was identified as a key factor for future successful development of the method
Tackling Immune Pathogenesis of COVID-19 through Molecular Pharmaceutics
Full text linkAn increasing number of clinical studies worldwide are investigating the repurposing of antiviral, immune-modulatory, and anti-inflammatory agents to face the coronavirus disease-19 (COVID-19) pandemic. Nevertheless, few effective therapies exist to prevent or treat COVID-19, which demands increased drug discovery and repurposing efforts. In fact, many currently tested drugs show unknown efficacy and unpredictable drug interactions, such that interventions are needed to guarantee access to effective and safe medicines. Anti-inflammatory therapy has proven to be effective in preventing further injury in COVID-19 patients, but the benefit comes at a cost, as targeting inflammatory pathways can imply an increased risk of infection. Thus, optimization of the risk/benefit ratio is required in the anti-inflammatory strategy against COVID-19, which accounts for drug formulations and delivery towards regionalization and personalization of treatment approaches. In this perspective, we discuss how better knowledge of endogenous immunomodulatory pathways may optimize the clinical use of novel and repurposed drugs against COVID-19 in inpatient, outpatient, and home settings through innovative drug discovery, appropriate drug delivery systems and dedicated molecular pharmaceutics
Microencapsulation of microbial derived indoles by spray drying
No full textThe indoles produced by human flora show potential activity against resistant pathogens and modulate inflammation and immunity, thus acting on both the host and microbiome. Indole-3-aldehyde (3-IAld), produced by host’s Lactobacilli, has recently been shown to preserve immune physiology at mucosal surfaces while inducing antimicrobial resistance. (23973224). The potential therapeutic action of 3-IAld is ascribable to its main target: the aryl hydrocarbon receptors (AHR) mainly located in the small intestine region.
For this reason, the aim of the present study is to develop an 3-IAld gastro-resistant formulation for small intestine (SI) regional drug delivery. In this regard, the purpose is to limit drug release in the stomach to avoid undesired effect and to ensure controlled release in the proximal small intestine. Therefore, microencapsulation methods will be employed (17207416). For this purpose, we encapsulated 3-IAld in methacrylate microparticles (MP) (Eudragit) prepared by spray-drying technique. The spray-drying method is a fast-way to produce dry particles, controlling particle size, morphology and allowing control of particle’s properties. (19862804). However, attention should be taken in the determination of working conditions and equipment setup to reduce the chance of producing porous and irregular MP that may not warrant the wanted SI localization. Moreover, 3-IAld shows tendency to diffuse either in aqueous or polar organic solvents during polymer layer formation, reducing entrapment efficiency with part of 3-IAld localized on the surface of the MP.
Different Eudragit types were employed, among them, S100 and L100 show the most desirable attributes in terms of pH solubility (pH ≥ 6.0 and ≥ 7.0, respectively). (10789067). Eudragit L100-S100 in combination (1:1), (1:3), (1:4) were used to prepare the MP and different ethanol-water solutions. The MP were evaluated for particle size, shape, surface morphology and elemental analysis, yield, drug content (DC), and were tested in vitro for their pH-dependent release by using simulated gastric and intestinal fluids. Initial formulations at 1:1 L100-S100 ratio showed high gastric release exceeding 50-60% at 1.5 hours. The release burst was correlated to high porosity and irregular shape of the obtained MP. Average DC was between 5-10% w/w. At 1:3 L100-S100 ratio the release dropped to about 30% and DC was increased up to 20% w/w.
Spray-drying conditions were then set in order to shift toward a non-buckling condition in which denser and less porous MP are formed. In such a way, 3-IAld release was further reduced to nearly 20% at 1.5 hours. The MP obtained seem to be promising to be employed to deliver 3-IAld to the SI. Ongoing studies are aimed at reducing further 3-IAld gastric release while increasing drug content
Engineering carrier nanoparticles with biomimetic moieties for improved intracellular targeted delivery of mRNA therapeutics and vaccines
No full textBiological membrane-engineered lipid nanoparticles (LNP) have shown enormous potential as vehicles for drug delivery due to their outstanding biomimetic properties. To make these nanoparticles more adaptable to complex biological systems, several methods and cellular sources have been adopted to introduce biomembrane-derived moieties onto LNP and provide the latter with more functions while preserving their intrinsic nature. In this review, we focus on LNP decoration with specific regard to mRNA therapeutics and vaccines. The bio-engineering approach exploits a variety of biomembranes for functionalization, such as those derived from red blood cells, white blood cells, cancer cells, platelets, exosomes, and others. Biomembrane engineering could greatly enhance efficiency in targeted drug delivery, treatment, and diagnosis of cancer, inflammation, immunological diseases, and a variety of pathologic conditions. These membrane-modification techniques are expected to advance biomembrane-derived LNP into wider applications in the future
Biodrug Delivery Systems: Do mRNA Lipid Nanoparticles Come of Age?
No full textAs an appealing alternative to treat and prevent diseases ranging from cancer to COVID-19, mRNA has demonstrated significant clinical effects. Nanotechnology facilitates the successful implementation of the systemic delivery of mRNA for safe human consumption. In this manuscript, we provide an overview of current mRNA therapeutic applications and discuss key biological barriers to delivery and recent advances in the development of nonviral systems. The relevant challenges that LNPs face in achieving cost-effective and widespread clinical implementation when delivering mRNA are likewise discussed
Development of Novel Indole-3-Aldehyde–Loaded Gastro-Resistant Spray-Dried Microparticles for Postbiotic Small Intestine Local Delivery
No full textConsidering the recent evidences on the therapeutic potential of post-biotics, this study was focused on two mains goals: i) to develop an enteric microparticle (MP) formulation for intestinal localized delivery of Indole-3-aldehyde (3-IAld) (a microbial-derived metabolite produced by the host's lactobacilli during the catabolic pathway of tryptophan); ii) to provide support to the employment of spray-drying as innovative one-step manufacturing technique for enteric products. For this purpose, special attention was taken in the knowledge of the influence of equipment setup and feedstock properties on MP enteric behaviour. Eudragit® S100 and L100 and ethyl cellulose were used as wall materials and NaOH and ethanol solutions as solvent systems. 3-IAld loading was maintained at 10% w/w. As postulated, feedstock properties influenced spray-drying regime. In addition, they prevailed over other spray-drying process factors in determining MP enteric behavior. Albeit the high buckling regime that produced crumped particles, gastro-resistance was obtained by spray-drying 2:1 Eudragit® S100:L100 with 30% w/w ethyl cellulose (EC) in ethanol solution. These results support the use of spray-drying as a method for manufacturing gastro-resistant MP. The obtained 3-IAld loaded enteric MP will be useful to investigate novel post-biotic-based treatments in different therapeutic areas
Harnessing inter-kingdom metabolic disparities at the human-fungal interface for novel therapeutic approaches
No full text: Humans interact with a multitude of microorganisms in various ecological relationships, ranging from commensalism to pathogenicity. The same applies to fungi, long recognized for their pathogenic roles in infection-such as in invasive fungal diseases caused, among others, by Aspergillus fumigatus and Candida spp.-and, more recently, for their beneficial activities as an integral part of the microbiota. Indeed, alterations in the fungal component of the microbiota, or mycobiota, have been associated with inflammatory, infectious and metabolic diseases, and cancer. Whether acting as opportunistic pathogens or symbiotic commensals, fungi possess a complex enzymatic repertoire that intertwines with that of the host. In this metabolic cross-talk, fungal enzymes may be unique, thus providing novel metabolic opportunities to the host, or, conversely, produce toxic metabolites. Indeed, administration of fungal probiotics and fungi-derived products may be beneficial in inflammatory and infectious diseases, but fungi may also produce a plethora of toxic secondary metabolites, collectively known as mycotoxins. Fungal enzymes may also be homologues to human enzymes, but nevertheless embedded in fungal-specific metabolic networks, determined by all the interconnected enzymes and molecules, quantitatively and qualitatively specific to the network, such that the activity and metabolic effects of each enzyme remain unique to fungi. In this Opinion, we explore the concept that targeting this fungal metabolic unicity, either in opportunistic pathogens or commensals, may be exploited to develop novel therapeutic strategies. In doing so, we present our recent experience in different pathological settings that ultimately converge on relevant trans-kingdom metabolic differences
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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