1,721,008 research outputs found
Spray congealed lipid microparticles for the local delivery of β-galactosidase to the small intestine
No full textOral local delivery of therapeutic biologics is generally limited due to the multiple obstacles of the gastrointestinal (GI) tract, mainly represented by acidic stomach pH and digestive enzymes. In the present study, spray congealing was used to prepare solid lipid microparticles (SLMs) loaded with β-galactosidase (lactase), an enzyme used for the treatment of lactose intolerance, to achieve a local drug delivery to the small intestine. Lactase was characterized in terms of activity at different pH, kinetic parameters and proteolytic degradation by digestive enzymes. Then, five lipid excipients were used to prepare unloaded SLMs, which were tested regarding lipase-induced digestion. The lipid with the best performance (glyceryl trimyristate) was used to prepare lactase-loaded SLMs. Spray congealed SLMs were spherical with very good encapsulation efficiency (>95%). The ability of the SLMs to protect the enzyme from the degradation in gastric environment was correlated with the particle size and the best formulation preserved the lactase activity up to 70%. Lactase was promptly released in simulated intestinal environment, and an in vitro positive food effect was observed. The present study demonstrated the potential of spray congealing for the preparation of solid lipid formulations able to achieve local oral delivery of a biologic drug
Development of flexible and dispersible oral formulations containing praziquantel for potential schistosomiasis treatment of pre-school age children
No full textPraziquantel (PZQ), an anthelmintic drug used in developing countries for the treatment of schistosome infections, was processed using the fluid bed wet granulation technology to prepare fast dispersible granules, as an appropriate and flexible dosage form for pre-school-aged children. Granulation experiments were performed incorporating PZQ either in the powder mixture, according to the traditional way, or in the liquid phase containing wetting agents. In the powder mixture several excipients were tested: Flowlac 100 as filler, Galeniq 721 (isomalt) and Neosorb P 100 T (D-sorbitol) as sweeteners and PVP K30 as binder; while in the liquid phase Lutrol F68, Cremophor RH 40 or Tween 80 as surfactants were investigated. Different formulations loaded with 10% w/w (batches 1-8) and 20% w/w of PZQ (batches 9-13) were produced The majority of granules displayed good flow properties and uniform drug content. X-ray powder diffraction showed that PZQ remained in its original crystalline state, while differential scanning calorimetry and Fourier transform-infrared analysis evidenced the formation of chemical interactions among the ingredients. The solubilisation test performed in non-sink condition to reproduce the actual condition in which a child of 4 years takes the medicine revealed that granules quickly formed a very fine suspension in water (dV90 = 39.9 μm). Although after the granulation process the solubility of raw PZQ was not increased, adding the aqueous suspension to 500 ml of buffer solution of pH 1.5, simulating the fasted state of a child, 50% of the drug was dissolved after 30 min. After granule manipulation with milk and fruit juices, no PZQ degradation was observed during time. Finally, the selected granule formulation provided evidence to be stable even at hot and very humid climate (30°C/75% RH), at least for the examined time
A novel approach for dry powder coating of pellets with Ethylcellulose. Part I: Evaluation of film formulation and process set up
No full textAn innovative dry powder coating technology was developed in a high-shear granulator using ethylcellulose (E10) as polymer. Several solid plasticizers were investigated with the aim of decreasing the polymer Tg at least to the highest possible working temperature (80°C). DSC analysis of physical mixtures of E10 and plasticizers evidenced that lauric acid (LA) was the most effective plasticizer. In order to reach the target temperature a liquid plasticizer, oleic acid (OA), was introduced in the coating formulation. Free films were then prepared and the target minimum film forming temperature (MFFT) was established in the range 70-80°C. Depending on the LA:OA weight ratio, Kollidon VA64 was included to decrease the LA recrystallization, while talc served as anti-sticking agent. Curing at the MFFT ensured the formation of homogeneous and stable films with good stability on storage. The dry powder coating process of placebo pellets was then developed, consisting of a combination of liquid assisted and thermal adhesion methods. The best coating formulations in terms of yields, coating efficiency (expressed as Relative Standard Deviation of the weight applied) and low pellets aggregation were based on E10:LA:OA in a weight ratio of 65:20:15 and 60:20:20. Moreover pellets remained stable after 1 year of storage (25°C/60% R.H.)
Composite of Elastin-Based Matrix and Electrospun Poly(L-Lactic Acid) Fibers: A Potential Smart Drug Delivery System
Full text linkStimuli-responsive hydrogel matrices are inspiring manifold applications in controlled delivery of bioactive compounds. Elastin-derived polypeptides form hydrogel matrices that may release bioactive moieties as a function of local increase of active elastases, as it would occur in several processes like inflammation. In view of the development of a patch for healing wounds, recombinant elastin-based polypeptides were combined with a proteolysis-resistant scaffold, made of electrospun poly-L-lactic acid (PLLA) fibers. The results of this study demonstrated the compatibility of these two components. An efficient procedure to obtain a composite material retaining the main features of each component was established. The release of the elastin moiety was monitored by means of a simple protocol. Our data showed that electrospun PLLA can form a composite with fusion proteins bound to elastin-derived polypeptides. Therefore, our approach allows designing a therapeutic agent delivery platform to realize devices capable of responding and interacting with biological systems at the molecular level
Modulation of Alendronate release from a calcium phosphate bone cement: An in vitro osteoblast-osteoclast co-culture study
No full textIn this study, we loaded a biomimetic calcium phosphate bone cement (CPC) with relatively high amounts of a
bisphosphonate through the use of Solid Lipid Microparticles (MPs) and investigated bone cells response to the
composite cements. 10, 20 and 30% w/w of Alendronate (AL) were successfully introduced into microparticles of
Cutina HR and Precirol, which were prepared by means of spray-congealing technique. Addition of AL-loaded MPs to
the cement composition provoked a lengthening of the setting and of the hardening processes. However, setting times
were still in a range useful for clinical applications, except for the cements at the highest Alendronate content. The
composite cements displayed a sustained drug release over time. Cements with the best performances in terms of
setting, hardening, mechanical properties and drug release were submitted to in vitro tests using a co-culture model of
osteoblast and osteoclast. The results showed that the use of MPs to enrich the cement composition with Alendronate
provides materials able to inhibit osteoclast viability and activity, while promoting osteoblast viability and earlier
differentiation, indicating that the MPs-cements are good delivery systems for bisphosphonates
A Novel Approach for Dry Powder Coating of Pellets with Ethylcellulose. Part II: Evaluation of Caffeine Release
No full textThe objective of this study was to assess the efficacy and the capability of a novel ethylcellulose-based dry-coating system to obtain prolonged and stable release profiles of caffeine-loaded pellets. Lauric and oleic acids at a suitable proportion were used to plasticize ethylcellulose. The effect of coating level, percentage of drug loading, inert core particle size, and composition of the coating formulation including the anti-sticking agent on the drug release profile were fully investigated. A coating level of 15% w/w was the maximum layered amount which could modify the drug release. The best controlled drug release was obtained by atomizing talc (2.5% w/w) together with the solid plasticizer during the dry powder-coating process. SEM pictures revealed a substantial drug re-crystallization on the pellet surface, and the release studies evidenced that caffeine diffused through the plasticized polymer acting as pore former. Therefore, the phenomenon of caffeine migration across the coating layer had a strong influence on the permeability of the coating membrane. Comparing dry powder-coated pellets to aqueous film-coated ones, drug migration happened during storage, though more sustained release profiles were obtained. The developed dry powder-coating process enabled the production of stable caffeine sustained release pellets. Surprisingly, the release properties of the dry-coated pellets were mainly influenced by the way of addition of talc into the dry powder-coating blend and by the drug nature and affinity to the coating components. It would be interesting to study the efficacy of novel coating system using a different API
Spray-congealed Solid Lipid Microparticles as a new tool for the controlled release of Bisphosphonates from a Calcium Phosphate Bone cement
Full text linkThe aim of this work was to develop an innovative drug delivery system potentially useful for the local delivery of Bisphosphonates to bone tissue. We propose the use of Solid Lipid Microparticles (MPs), up to now mainly used for oral and topical drug delivery, as carrier for bisphosphonates due to the favourable biocompatibility and lower toxicity of the lipids compared with many polymers. The delivery platform consisted of a biomimetic α-tricalcium phosphate-gelatin cement (CPC) enriched with alendronate loaded MPs (MPs-AL) produced by the spray congealing technology. Alendronate direct addition to cement composition is limited since Alendronate is able to sequester calcium from calcium phosphates, thus preventing the setting of the cements. At variance, this approach permitted to load a relatively high amount of the drug on the CPC and allowed the controlled release of the highly water soluble alendronate. A Design of Experiment (DoE) was employed for the screening of the effects of the formulation variables related to the presence of unloaded microparticle (MPs) on the cement most important mechanical properties. Then, MPs loaded with 10 % w/w of alendronate were produced using five different carriers (Stearic Acid, Stearilic Alcohol, Cutina HR, Tristearin and Precirol ATO5). All MPs-AL exhibited a spherical shape, encapsulation efficiency higher than 90% and prevalent particle size ranging from 100-150 micron. Solid state characterization (DSC, HSM and X-ray powder diffraction) demonstrated that encapsulation of alendronate into MPs did not alter its crystal structure. MPs-AL addition to the cement provoked a modest lengthening of the setting times and of the hardening reaction leading to the complete transformation of α-tricalcium phosphate into calcium-deficient hydroxyapatite, without significantly affect the cement mechanical properties. Moreover, the results of in vitro AL release study performed on cements enriched with MPs-AL showed that the system allows a controlled release of the drug over time
Influence of the extraction method on functional properties of commercial snail secretion filtrates
Full text linkAbstract Snail secretion is a complex mixture of several components, including proteins, glycoproteins, mucopolysaccharides and smaller molecules. Its growing use in nutraceutical, cosmetic and biomedical applications, as well as a component of edible and green packaging to replace chemical plasticizer, implies more affordable and sustainable extraction methods. We chose four extracts obtained from Cornu aspersum snails, different by origin, extraction medium (namely, citric acid, lactic acid or none) and additives and we performed a series of characterizations including the SDS-page, the measure of pH and density, the evaluation of dry matter and of protein content, supported by structural determinations by means of UV-visible and infrared spectroscopy, X-Rays diffraction and thermogravimetric measurements. Biological assays comprising evaluation of cytotoxicity and antibacterial activity were also carried out. All the tests were performed both on the as received snail filtrates and on the samples after proper dialysis to remove preservatives added by manufacturers. The obtained results put into evidence that the properties and composition of the final extract are strongly influenced by the collection method, that can be relevant for the proper use of snail filtrate in specific applications
Sviluppo di gas diffusion electrodes per la reazione di evoluzione di idrogeno in elettrolizzatori AEM
Full text linkLo sviluppo di elettrolizzatori a membrana a scambio anionico (AEM) rappresenta una delle strategie più promettenti per la produzione sostenibile di idrogeno, grazie alla possibilità di utilizzare catalizzatori privi di metalli nobili e a basso costo. In questo lavoro di tesi è stata condotta la sintesi e l’ottimizzazione di catalizzatori a base di Layered Double Hydroxide (LDH), ottenuti mediante elettrodeposizione su differenti supporti conduttivi (schiume di Ni e carbon paper). Sono stati sintetizzati diversi catalizzatori variando la natura dei metalli di transizione (Ni, Fe, Co, Mn) e le relative concentrazioni molari, con l’obiettivo di valutare l’influenza della composizione e del rapporto tra i cationi sulle proprietà elettrocatalitiche. Una prima selezione è stata effettuata mediante voltammetria a scansione lineare (LSV), individuando come sistema più promettente il catalizzatore CoFe 2:1. A partire da questo materiale sono state introdotte modifiche procedurali – tra cui l’ottimizzazione del numero di cicli di elettrodeposizione, trattamenti di attivazione riduttiva, calcinazione, doppia deposizione e impregnazione con nanoparticelle di platino – al fine di migliorarne ulteriormente attività e stabilità operativa nella reazione di evoluzione dell’idrogeno (HER). I catalizzatori sono stati caratterizzati mediante tecniche elettrochimiche (cronopotenziometria, analisi di Tafel slope) e morfologiche (SEM, ECSA) ed infine testati in una cella elettrochimica in flusso con membrana AEM, valutandone le prestazioni complessive di cella. I risultati hanno evidenziato un’attività competitiva e una buona stabilità a lungo termine, confermando la validità dell’approccio adottato nello sviluppo di elettrodi catalitici per elettrolizzatori AEM
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