Polysaccharide-based self-assembling nanohydrogels: An overview on 25-years research on pullulan

The aim of this overview is to review the evolution of the studies carried out, during more than 25 years, on nanohydrogels obtained by self-assembling of pullulan (PUL) using several hydrophobization strategies. After the first publications, mainly devoted to the preparation and characterization of PUL nanogels, a remarkable number of studies demonstrated how wide can be the field of applications within the main topic of biopharmaceutics. Numerous hydrophilic and lipophilic drugs were entrapped in the nanogel networks, consequently PUL nanogels have been proposed as delivery systems for single drugs and for combination therapies which allowed improvements of pharmacological activities and patient compliance. Furthermore, the large amount of water content allowed loading also proteins which could maintain their native structure and properties. Stimuli-sensitive and stealth PUL nanogel formulations allowed improving the performances of antitumor drugs. These nanohydrogels have also been studied for imaging techniques and for vaccines to be administered by injection and by mucosal application. The studies on PUL nanogels are still in progress and the perspectives for future researches are also addressed

Estudo da utilização de polissacarídeos no desenvolvimento de formulações de liberação prolongada: goma de semente de algaroba, goma xantana e quitosano

O objetivo deste trabalho foi o desenvolvimento de novos sistemas de matrizes hidrofílicas através da formação de ligações cruzadas (cross-linking) entre a Goma da Semente da Algaroba (GSA), uma galactomanana que ocorre no endosperma das sementes de uma árvore nativa do Brasil, a Prosopis juliflora DC, e dois polissacarídeos bem conhecidos pela sua habilidade de retardar a liberação de fármacos, quitosano e goma xantana, visando a utilização das novas substâncias na preparação de formas orais de liberação prolongada. O estudo iniciou com a avaliação da funcionalidade GSA como matriz hidrofílica. A seguir, iniciamos o estudo do perfil de absorção de água dos polímeros envolvidos (GSA, Quitosana e goma xantana), nos seguintes meios: água, SGF e SIF. Na etapa seguinte, procuramos pelo melhor agente formador de ligação cruzada, entre os dois encontrados em literatura, glutaraldeído (GA) e hexametilenodiisocianato (HMDI). Sendo que a GA se apresentou como o melhor agente pelos resultados apresentados. O próximo passo foi a preparação e avaliação de novas matrizes hidrofílicas de GSA_Quitosana e GSA_Goma Xantana, com proporções diferentes, 1:1, 1:2 e 2:1. Finalmente, após a escolha do sistema hidrofílico que apresentou os melhores resultados, utilizando as ferramentas estatísticas, investigamos o mecanismo de controle da liberação do fármaco modelo. Por fim concluímos que a melhor combinação de polissacarídeos foi conseguida com a GSA e a goma xantana, na proporção de 1:2, utilizando solução de glutaraldeído como agente de formação de ligação cruzada. Esta nova matriz apresentou cinética de ordem zero, que é fundamental em uma substância a ser utilizada em formulações orais sólidas de liberação prolongada.The aim of this work was to design new hydrophilic matrix (HM) systems by cross-linking Mesquite Seed Gum (MSG), a galactomannan that occurs in the endosperm layer of the seeds of a Brazilian tree,Prosopis juliflora DC, with two well-known polysaccharides with the ability of retarding drug release, chitosan and xanthan gum. This had in mind the idea of using these new compounds in the preparation of extended-release dosage oral forms. The first part of this study was dedicated to the evaluation of MSG in terms of its functionality as a hydrophilic matrix (HM) system for extended-release purposes. Next, we started the study of water uptake profile of all polymers of interest (MSG, Xanthan Gum and Chitosan), in the following media: water, SGF and SIF. Following, we searched for the best cross-linking agent between Glutharaldehyde (GA) and Hexamethylenediisocyanate (HMDI), which turned out to be the GA. Next step we begun to prepare new hydrophilic matrices of MSG_Chitosan and MSG_Xanthan Gum, with different ratios, 1:1, 1:2 and 2:1. Finally, after deciding which new HM system presented best results, by using statistics tools, we investigated the mechanism controlling the rate release of the model drug, from tablets made with this new matrix. As a final result we concluded that the best combination of polysaccharides was achieved with MSG and Xanthan Gum, with mass ratio of 1:2, using glutharaldehyde aqueous solution as cross-linking agent. It presented a prevalent zero order kinetics, which is a very important feature when thinking about an extended-release oral dosage

In situ forming IPN hydrogels of calcium alginate and dextran-HEMA for biomedical applications

AbstractIn situ forming hydrogels, which allow for the modulation of physico-chemical properties, and in which cell response can be tailored, are providing new opportunities for biomedical applications. Here, we describe interpenetrating polymer networks (IPNs) based on a physical network of calcium alginate (Alg-Ca), interpenetrated with a chemical one based on hydroxyethyl-methacrylate-derivatized dextran (dex-HEMA). IPNs with different concentration and degree of substitution of dex-HEMA were characterized and evaluated for protein release as well as for the behavior of embedded cells. The results demonstrated that the properties of the semi-IPNs, which are obtained by dissolution of dex-HEMA chains into the Alg-Ca hydrogels, would allow for injection of these hydrogels. Degradation times of the IPNs after photocross-linking could be tailored from 15 to 180days by the concentration and the degree of substitution of dex-HEMA. Further, after an initial burst release, bovine serum albumin was gradually released from the IPNs over approximately 15days. Encapsulation of expanded chondrocytes in the IPNs revealed that cells remained viable and, depending on the composition, were able to redifferentiate, as was demonstrated by the deposition of collagen type II. These results demonstrate that these IPNs are attractive materials for pharmaceutical and biomedical applications due to their tailorable mechanical and degradation characteristics, their release kinetics and biocompatibility