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Synthesis of novel based saccharide polymers and their organization into nanoparticles
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Synthesis of novel saccharide-based polymers and their organization into nanoparticles
Publication . Raposo, Cláudia Diana de Castro Bizarro Gomes; Silva, Maria Teresa
Targeted drug delivery systems are an effective and attractive strategy for improving traditional therapies, currently used in medicine. However, their development presents itself as a great challenge since it is necessary to build them taking into account several factors: their biocompatibility, biodegradation, bioavailability, toxicity, efficacy and, of course, their cost of production and development.
In this work, functionalization strategies were developed for three commerciallyavailable polymers, namely poly(ethylene glycol) (PEG), epsilon-polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA), to obtain drug transport systems. PEG has the advantage of being an economically accessible polymer, however it is hydrophilic which hinders its transformation into stable polymeric nanoparticles in aqueous solution. PCL and PLGA are hydrophobic polymers, ideal for sustained release systems, however they have a high cost, comparatively. For lectin recognition in target cells, four different carbohydrates were used: glucose, galactose, xylose and mannose. Coumarins were also used, which in addition to having biological properties also provide fluorescent properties to these systems, which allows them to be used additionally for diagnostic purposes.
The commercially-available polymers were derivatized using simple reactions of esterification, amide formation, nucleophilic substitution, and cycloaddition (click chemistry reactions for the formation of triazoles), obtaining good yields with the exception of cycloaddition with unprotected sugar molecules whose yields were low, most likely due to the complexation of copper (I) with free hydroxyls. The use of known copper stabilizing additives did not reflect an increase in reaction yield.
The final polymers were transformed into polymeric nanoparticles using the oil-inwater emulsification with solvent evaporation technique both for PEG and PCL derivatives, and nanoprecipitation with solvent evaporation method for PLGA derivatives. Derivatives of PEG formed mostly polymeric films, most likely due to the small size of the hydrophobic part of the polymer (coumarin moiety).
In a preliminary test, the derivatives of PCL and PLGA were transformed into nanoparticles, but proper characterization regarding their encapsulation are needed. Nevertheless, the derivatives of PCL formed irregular spherical nanoparticles, with sizes ranging between 272 and 418 nm and low polydispersity indexes. Galacto-derivative formed a porous strucure with porous ranging from 1.6 to 3:6µm. A coumarin-derivative produced parallelepiped-like particles, with average height and width of 492 and 303 nm, respectively.
PLGA derivatives formed stable spherical nanoparticles in aqueous solution (with the exception of the xylopyranose derivative that showed low stability, and a coumarin derivative that did not form particles), with smooth surface and with sizes between 157 and 195 nm and low rates of polydispersity.
Human lectins, their carbohydrate affinities and where to find them
Publication . Raposo, Cláudia D.; Canelas, André B.; Barros, M. Teresa; LAQV@REQUIMTE; DQ - Departamento de Química; MDPI - Multidisciplinary Digital Publishing Institute
Lectins are a class of proteins responsible for several biological roles such as cell-cell interactions, signaling pathways, and several innate immune responses against pathogens. Since lectins are able to bind to carbohydrates, they can be a viable target for targeted drug delivery systems. In fact, several lectins were approved by Food and Drug Administration for that purpose. Information about specific carbohydrate recognition by lectin receptors was gathered herein, plus the specific organs where those lectins can be found within the human body.
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Fundação para a Ciência e a Tecnologia
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OE
Número da atribuição
PD/BD/109680/2015