Les matériaux hydroxydes doubles lamellaires (HDL) sont une classe d'argiles anioniques synthétiques dont la structure est basée sur celle du brucite Mg(OH)2 dans lesquelles une partie des cations métalliques divalents sont été remplacés par des ions trivalents donnant ainsi des feuillets chargés positive. Cette charge est équilibrée par l'intercalation d'anions dans la région interlamellaire hydratée. Les identités et les rapports des cations di- et trivalents et l'anion interlamellaire peuvent être varié sur une large gamme, donnant lieu à une large classe de matériaux isostructurales. Le matériau d’origine de cette classe est l’hydrotalcite (HT) et les HDL sont par conséquent également connus comme des matériaux de type hydrotalcite. Bien que les caractéristiques de base de la structure soient bien comprises, des aspects structurels détaillés ont fait l'objet de certaine controverse dans la littérature afin de maîtriser leurs propriétés et leurs applications potentielles. Dans ce travail de thèse nous avons retenu deux types de HDL MgAl et ZnAl qui ont été largement introduits dans diverses applications, tels que la sorption des molécules d'intérêt biologique (enzyme et médicament) et l'élaboration d'électrodes. La spécificité de ce travail repose sur l’immobilisation d’une enzyme modèle, la lactate déshydrogénase dans ces deux matrices ainsi qu’un médicament anti-bactérien, la berbérine, afin d’étudier les interactions entre ces deux biomolécules et la phase HDL introduite et de répondre à leurs exigences d'applications dans le domaine médical. Dans un second temps nous avons tenté d’étudier les deux phases mentionnées de plus en plus fine en termes de structure, morphologie et profil électrochimique en vue de les employer en tant que matériaux d’électrode pour le développement de biopile / DHs are a class of synthetic anionic clays whose structure is based on brucite-like layers Mg(OH)2 inwhich some of the divalent cations have been replaced by trivalent ions giving positively-charged sheets.This charge is balanced by intercalation of anions in the hydrated interlayer regions. The identities andratios of the di- and trivalent cations and the interlayer anion may be varied over a wide range, giving rise toa large class of isostructural materials. The parent material of this class is the naturally occurring mineralhydrotalcite and LDHs are consequently also known as hydrotalcite-like materials. Although the basicfeatures of the structure are well understood, detailed structural aspects have been the subject of somecontroversy in the literature. In this thesis, we have selected two types of LDH, MgAl and ZnAl, which havebeen widely introduced in various applications, such as sorption of molecules of biological interest (enzymeand drug) and the development of electrodes. The specificity of this work lies on the immobilization of amodel enzyme, lactate dehydrogenase in both matrices as well as an anti-bacterial drug, berberine, inorder to study the interactions between these two biomolecules and the introduced LDH phase and tobetter address their challenges of applications in the medical field. Second, we have tried to study the twophases mentioned above more and more accurately in terms of structure, morphology and electrochemicalprofile in order to use them as electrode materials for microbial fuel cell device

Das bei der Sanierung von großen segmentalen Knochendefekten bestehende Risiko einer fremdkörperassoziierten Infektion soll durch die Integration eines Wirkstofffreisetzungssystems in ein bestehendes textiles Knochenimplantat gemindert werden. Durch Immobilisierung des Wirkstoffs in eine degradierbare Polymermatrix wird eine zeitlich verzögerte Freisetzung bewirkt. Als Wirkstofffreisetzungssystem wird die Kombination von Polylactid (PLA) bzw. Poly(Lactid-co-Glycolid) (PLGA) als Matrixpolymer mit dem Antibiotikum Gentamicin als Wirkstoff untersucht, welches durch Beschichtung der textilen Scaffolds mittels Dip-Coating eingebracht werden soll. Es stehen die drei Beschichtungsmethoden „Suspension“, „Emulsion“ und „Schichtaufbau“ zur Auswahl, die jeweils über eigene Parameter zur Beeinflussung des Freisetzungsprofils verfügen. Die Methode „Suspension“ und die damit verbundenen Einflussfaktoren Korngröße, Korngrößenverteilung sowie Masseanteil des Antibiotikums und Schichtdicke der aufgetragenen Polymerschicht wurde als die günstigste herausgearbeitet. Im Teil II dieser Arbeit wird diese soweit optimiert, dass nahezu über den gesamten geforderten Zeitraum die festgelegte notwendige Dosierung aufrechterhalten werden kann. Erste in vitro Versuche weisen auf eine gute Zellverträglichkeit sowie eine ausreichende mikrobielle Wirksamkeit hin. / To reduce the risk of infection in the treatment of long bone defects, a novel embroidered bone implant is to be provided with an antibiotic drug delivery system. Prolonged and controlled drug release can be achieved by coating the thread material with antibiotics incorporated in a degradable polymer matrix. The chosen drug delivery system is composed of polylactide acid (PLA) or poly(lactide-co-glycolide) acid (PLGA) as matrix polymer and the antibiotic gentamicin. It is integrated into the textile structure by dip-coating providing the three different methods suspension, emulsion and layered. Each method bears its appropriate parameters to influence the releasing profile. The suspension-method and its parameters grain size and grain size distribution as well as mass fraction of the antibiotic and the coating thickness could be proved as the most feasible. In part II of this essay the chosen coating set-up gets optimized so that a drug release nearly along the whole required term can be achieved. Preliminary in vitro studies show a good cell tolerance besides a sufficient microbial efficacy.

Hyaluronan is a chemical, which can be qualified as essential for vertebrates. It is a part of the extracellular matrix in most of tissues and also a major component of some other tissues. Besides of the mechanical functions this compound is important for many biological processes such as growth of tumor cells. The objective of this thesis was development of carrier systems containing native hyaluronan and hydrophobic drugs. For purposes of this work fluorescence probes (pyrene, prodan, perylene, DPH, mereocynine 540) instead of drugs were used. By using further mentioned sophisticated methods the properties of these systems were studied. The systems were prepared by freeze-drying. The effect of freeze-drying on support of interactions was observed by fluorescence spectrometry (steady-state and time-resolved). The stability of freeze-dried systems was determined by zeta potential, which was measured by electrophoretic light scattering. Cakes obtained by freeze-drying were analyzed by several methods. First one was effluence gas chromatography connected with FT-IR spectrometry. In this method the present of tertiary butyl alcohol in product was observed. The cakes were also analyzed by scanning electron microscopy, which can provide the information about the surface and elemental constitution of the material. The results of this work can shed light on the area of developing of drugs with targeted distribution of active compound.

Das bei der Sanierung von großen segmentalen Knochendefekten bestehende Risiko einer fremdkörperassoziierten Infektion soll durch die Integration eines Wirkstofffreisetzungssystems in ein bestehendes textiles Knochenimplantat gemindert werden. Durch Immobilisierung des Wirkstoffs in eine degradierbare Polymermatrix wird eine zeitlich verzögerte Freisetzung bewirkt. Als Wirkstofffreisetzungssystem wird die Kombination von Polylactid (PLA) bzw. Poly(Lactid-co-Glycolid) (PLGA) als Matrixpolymer mit dem Antibiotikum Gentamicin als Wirkstoff untersucht, welches durch Beschichtung der textilen Scaffolds mittels Dip-Coating eingebracht werden soll. Es stehen die drei Beschichtungsmethoden „Suspension“, „Emulsion“ und „Schichtaufbau“ zur Auswahl, die jeweils über eigene Parameter zur Beeinflussung des Freisetzungsprofils verfügen. Die Methode „Suspension“ und die damit verbundenen Einflussfaktoren Korngröße, Korngrößenverteilung sowie Masseanteil des Antibiotikums und Schichtdicke der aufgetragenen Polymerschicht wurde als die günstigste herausgearbeitet. Im Teil II dieser Arbeit wird diese soweit optimiert, dass nahezu über den gesamten geforderten Zeitraum die festgelegte notwendige Dosierung aufrechterhalten werden kann. Erste in vitro Versuche weisen auf eine gute Zellverträglichkeit sowie eine ausreichende mikrobielle Wirksamkeit hin. / To reduce the risk of infection in the treatment of long bone defects, a novel embroidered bone implant is to be provided with an antibiotic drug delivery system. Prolonged and controlled drug release can be achieved by coating the thread material with antibiotics incorporated in a degradable polymer matrix. The chosen drug delivery system is composed of polylactide acid (PLA) or poly(lactide-co-glycolide) acid (PLGA) as matrix polymer and the antibiotic gentamicin. It is integrated into the textile structure by dip-coating providing the three different methods suspension, emulsion and layered. Each method bears its appropriate parameters to influence the releasing profile. The suspension-method and its parameters grain size and grain size distribution as well as mass fraction of the antibiotic and the coating thickness could be proved as the most feasible. In part II of this essay the chosen coating set-up gets optimized so that a drug release nearly along the whole required term can be achieved. Preliminary in vitro studies show a good cell tolerance besides a sufficient microbial efficacy.

No description available.

No description available.

The thesis is focused on the research of stability of controlled drug release systems based on a blend of plasticized starch/polycaprolactone (TPS/PCL) that served as a carrier. Antibiotic vancomycin was used as a model drug, and its release from TPS/PCL pellets into aqueous environment was followed by UV-spectroscopy and the obtained time dependences were treated by a simple kinetic model. Moreover, the simultaneous release of starch particles to the surrounding liquid phase was studied by static and dynamic light scattering as well as transmission electron microscopy (TEM) in order to obtain information on the stability of biodegradable matrix and on the structure of the products of the pellet decomposition on a nanoscale level. Key words: vancomycin, starch, drug delivery system, polycaprolactone (PCL), particle release, dynamic light scattering (DLS), static light scattering (SLS)

The past few years have witnessed significant work being directed towards drug delivery systems with layer-by layer (LbL) technique prominently featured as one of the most sought after approach. However, majority of the studies were focused on the fabrication of microcapsules which produced numerous drawbacks resulting in reduced applicability. This has spurred research into nanocapsules which has proved to overcome most of the drawbacks that plagued microcapsules by being able to evade the reticulo-endothelial system, exhibit enhanced permeability and retention in tumours etc. The capsules fabricated by the LbL technique requires a suitable combination of cationic and anionic polyelectrolytes which ensures that it is able to effectively protect the cargo it encapsulates as well as enhance its bio-applications. With numerous advantages such as biocompatibility and biodegradability to name a few, chitosan has proved to be an ideal cationic polyelectrolyte. Thus, this thesis focuses on the various therapeutic applications of LbL fabricated chitosan based nanocapsules. The first work focuses on the targeted delivery of the somatostatin analogue, Octreotide conjugated nanocapsules to over expressed somatostatin receptors. These LbL fabricated nanocapsules composed of chitosan and dextran sulfate (CD) encapsulate the anti cancer drug, doxorubicin and are found to attain site specificity as well as enhanced anti-proliferative activity. The results indicated that the nanocapsules were biocompatible and when conjugated with octreotide was found to have an enhanced internalization into SSTR expressing cells, thereby making it a viable strategy for the treatment of tumors that has an over expression of somatostatin receptors such as pancreatic carcinoma, breast carcinoma etc. The objective of the second work was to develop an efficient drug delivery system such as CD nanocapsules for encapsulation of Ciprofloxacin in order to combat infection by Salmonella, an intracellular and intra-phagosomal pathogen. In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection. The increased retention of ciprofloxacin in tissues delivered by CD nanocapsules as compared to the conventional delivery proved that the same therapeutic effect was obtained with reduced dosage and frequency of Ciprofloxacin administration. The third work deals with the probiotic, Saccharomyces boulardii which is found to be effective against several gastrointestinal diseases but had limited clinical application due to its sensitivity to acidic environment. However, encapsulation of S. boulardii with chitosan and dextran sulfate ensured enhanced viability and selective permeability on exposure to acidic and alkaline conditions experienced during gastro intestinal transit. The final work involves the fabrication of novel pH responsive nanocapsules composed of chitosan-heparin which facilitate the intracellular delivery of a model anti-cancer drug, doxorubicin.

Chapter–I Introduction Shock waves appear in nature whenever the different elements in a fluid approach one another with a velocity larger than the local speed of sound. Shock waves are essentially non-linear waves that propagate at supersonic speeds. Such disturbances occur in steady transonic or supersonic flows, during explosions, earthquakes, tsunamis, lightening strokes and contact surfaces in laboratory devices. Any sudden release of energy (within few μs) will invariably result in the formation of shock wave since it is one of the efficient mechanisms of energy dissipation observed in nature. The dissipation of mechanical, nuclear, chemical, and electrical energy in a limited space will result in the formation of a shock wave. However, it is possible to generate micro-shock waves in laboratory using different methods including controlled explosions. One of the unique features of shock wave propagation in any medium (solid, liquid or gases) is their ability to instantaneously enhance pressure and temperature of the medium. Shock waves have been successfully used for disintegrating kidney stones, non-invasive angiogenic therapy and osteoporosis treatment. In this study, we have generated a novel method to produce micro-shock waves using micro-explosions. Different biological applications were developed by further exploring the physical properties of shock waves. Chapter – II Bacterial transformation using micro-shock waves In bacteria, uptake of DNA occurs naturally by transformation, transduction and conjugation. The most widely used methods for artificial bacterial transformation are procedures based on CaCl2 treatment and electroporation. In this chapter, controlled micro-shock waves were harnessed to develop a unique bacterial transformation method. The conditions have been optimized for the maximum transformation efficiency in E. coli. The highest transformation efficiency achieved (1 × 10-5 transformants per cell) was at least 10 times greater than the previously reported ultrasound mediated transformation (1 × 10-6 transformants per cell). This method has also been successfully employed for the efficient and reproducible transformation of Pseudomonas aeruginosa and Salmonella Typhimurium. This novel method of transformation has been shown to be as efficient as electroporation with the added advantage of better recovery of cells, economical (40 times cheaper than commercial electroporator) and growth-phase independent transformation. Chapter – III Needle-less vaccine delivery using micro-shock waves Utilizing the instantaneous mechanical impulse generated behind the micro-shock wave during controlled explosion, a novel non-intrusive needleless vaccine delivery system has been developed. It is well established, that antigens in the epidermis are efficiently presented by resident Langerhans cells, eliciting the requisite immune response, making them a good target for vaccine delivery. Unfortunately, needle free devices for epidermal delivery have inherent problems from the perspective of patient safety and comfort. The penetration depth of less than 100 µm in the skin can elicit higher immune response without any pain. Here the efficient utilization of the device for micro-shock wave mediated vaccination was demonstrated. Salmonella enterica serovar Typhimurium vaccine strain pmrG-HM-D (DV-STM-07) was delivered using our device in the murine salmonellosis model and the effectiveness of the delivery system for vaccination was compared with other routes of vaccination. The device mediated vaccination elicits better protection as well as IgG response even in lower vaccine dose (ten-fold lesser), compare to other routes of vaccination. Chapter – IV In vitro and in vivo biofilm disruption using shock waves Many of the bacteria secrete highly hydrated framework of extracellular polymer matrix on encountering suitable substrates and get embedded within the matrix to form biofilm. Bacterial colonization in biofilm form is observed in most of the medical devices as well as during infections. Since these bacteria are protected by the polymeric matrix, antibiotic concentration of more than 1000 times of the MIC is required to treat these infections. Active research is being undertaken to develop antibacterial coated medical implants to prevent the formation of biofilm. Here, a novel strategy to treat biofilm colonization in medical devices and infectious conditions by employing shock waves was developed. Micro-shock waves assisted disintegration of Salmonella, Pseudomonas and Staphylococcus biofilm in urinary catheters was demonstrated. The biofilm treated with micro-shock waves became susceptible to antibiotics, whereas the untreated was resistant. Apart from medical devices, the study was extended to Pseudomonas lung infection model in mice. Mice exposed to shock waves responded well to ciprofloxacin while ciprofloxacin alone could not rescue the mice from infection. All the mice survived when antibiotic treatment was provided along with shock wave exposure. These results clearly demonstrate that shock waves can be used along with antibiotic treatment to tackle chronic conditions resulting from biofilm formation in medical devices as well as biological infections. Chapter – V Shock wave responsive drug delivery system for therapeutic application Different systems have been used for more efficient drug delivery as well as targeted delivery. Responsive drug delivery systems have also been developed where different stimuli (pH, temperature, ultrasound etc.) are used to trigger the drug release. In this study, a novel drug delivery system which responds to shock waves was developed. Spermidine and dextran sulfate was used to develop the microcapsules using layer by layer method. Ciprofloxacin was loaded in the capsules and we have used shock waves to release the drug. Only 10% of the drug was released in 24 h at pH 7.4, whereas 20% of the drug was released immediately after the particles were exposed to shock waves. Almost 90% of the drug release was observed when the particles were exposed to shock waves 5 times. Since shock waves can be used to induce angiogenesis and wound healing, Staphylococcus aureus skin infection model was used to show the effectiveness of the delivery system. The results show that shock wave can be used to trigger the drug release and can be used to treat the wound effectively. A brief summary of the studies that does not directly deal with the biological applications of shock waves are included in the Appendix. Different drug delivery systems were developed to check their effect in Salmonella infection as well as cancer. It was shown for the first time that silver nanoparticles interact with serum proteins and hence the antimicrobial properties are affected. In a nutshell, the potential of shock waves was harnessed to develop novel experimental tools/technologies that transcend the traditional boundaries of basic science and engineering.

[EN] Nowadays, one of the biggest concerns that permanently keep the attention of main important sectors of human society is health. Modern medical science is compromised with not only providing good adequate treatments but also effective specific solutions for each type of disease or human pathology. In this direction, innovative approaches like tissue engineering or regenerative medicine, controlled drug delivery systems and nanomedicines emerge to bring alternatives to situations hard to solve with conventional treatment and strategies, including the replacement of damaged or diseases tissues and/or organs. Specifically, this research is mainly aimed to design a combined system for controlled, stable and localized release of therapeutic agents that are able to exert their effect selectively on the area that warrants treatment. This construct will have enough versatility to be adapted to almost any kind of treatment, from cancer to tissue regeneration, always that the key requirement of the treatment was the need to provide the treatment of localized, stable and controlled manner. With the purposes of making easier the understanding as well as the design of the system, I was decided, for the proof of concept, to use drugs and materials with known activity applied on tissue regeneration and for the treatment of chronic wounds. The system in question consists of three main elements: 1) The first element is the polymer conjugates of therapeutic agents, which contribute to increasing the selectivity of the therapeutic action of the drug, as well as improved stability, bioavailability and biocompatibility thereof. If the drug is hydrophobic, conjugation contributes to increase its solubility in water, and in the case of proteins used as therapeutic agents, the combination helps reduce the body's immune response, increasing the chance of successful of the treatment. 2) The second element are the biodegradable polymeric microparticles, which in this case act like encapsulation agents for polymeric conjugate , thus allowing to have a second control point in the release kinetics of the therapeutic agents . Simultaneously, the microparticles also play a role in modifying the texture of the final construct, ascribing mechanical and physicochemical properties that help to improve some biological properties of the final material, such as the affinity, adhesion and cell proliferation. 3) The third element consists of a nanoporous membrane made of a biodegradable polymer by electrospinning, which constitute the unifier element of the whole system. This membrane provides manageability to the construct and is itself the last point of control in the release kinetics of the therapeutic agent or agents. Besides, it must be biocompatible and stable at ambient conditions, since this probably is going to be exposed to the environment while protecting the wound, in the case of this kind of application. These three elements, which themselves are complex systems separately, are systematically combined to achieve a synergistic relationship between them so that each one power the qualities of the other two. The resulting construct was characterized and it demonstrated to have characteristic properties that can be used as a control parameter during manufacture of this new material. Also, preliminary biological studies developed "in vitro" indicated that the proposed system may be a good candidate for deeper studies as alternative treatment for chronic wounds and other pathologies that require localized administration for long periods of time. / [ES] Actualmente, una de las mayores preocupaciones que permanentemente laman la atención de los principales sectores de la sociedad humana es la salud. La ciencia médica moderna está comprometida no solo con suministrar tratamientos adecuados, sino más bien ofrecer soluciones efectivas y específicas para cada tipo de enfermedad o patología humana. En este sentido, estrategias innovadoras como la ingeniería de tejidos o la medicina regenerativa, los sistemas de liberación controlada de fármacos y las nanomedicinas, surgen como buenas alternativas para abordar situaciones difíciles de resolver aplicando los tratamientos y estrategias terapéuticas convencionales, como es el caso cuando se hace necesario reemplazar tejidos o incluso órganos dañados por algún traumatismo o enfermedad. Concretamente, el presente trabajo de investigación tiene por objetivo principal diseñar un sistema combinado para la liberación controlada, estable y localizada de agentes terapéuticos que sean capaces de ejercer su efecto de forma selectiva sobre la zona que amerita el tratamiento. Este constructo tendrá la versatilidad suficiente como para poder adaptarse a casi cualquier tipo de tratamiento, desde el cáncer hasta la regeneración de tejido, siempre que el requisito clave del tratamiento sea la necesidad de suministrar el tratamiento de manera localizada, estable y controlada. Para efectos de facilitar la compresión y el diseño del sistema se escogió para la prueba de concepto materiales y fármacos asociados a la regeneración de tejidos, como tratamiento para casos de heridas crónicas. El sistema en cuestión está constituido por tres elementos principales: 1) El primer elemento son los conjugados poliméricos de agentes terapéuticos que contribuirán a aumentar la selectividad de la acción terapéutica del fármaco, así como también a mejora la estabilidad, biodisponibilidad y biocompatibilidad de los mismos. En caso de que el fármaco sea hidrofóbico, la conjugación contribuye a aumentar su solubilidad en agua, y en el caso de usar proteínas como agentes terapéuticos, la conjugación contribuye a disminuir la respuesta inmunológica del cuerpo incrementando las posibilidad de éxito del tratamiento. 2) El segundo elemento son micropartículas poliméricas biodegradables, que en este caso actúan con agentes de encapsulación para los conjugados poliméricos, permitiendo así contar con un segundo punto de control en la cinética de liberación de los agentes terapéuticos. Simultáneamente, las micropartículas también cumplen un papel de modificador de la textura del constructo final, adjudicándole propiedades mecánica y fisicoquímicas que contribuyen a mejorar las propiedades biológicas del material final, como son la afinidad, la adhesión y la proliferación celular. 3) El tercer elemento consiste en una membrana polimérica biodegradable nanoporosa hecha por electrospinning, que constituyen el elemento unificados del sistema, aporta manejabilidad al constructo y es en sí mismo el último punto de control en la cinética de liberación del agente terapéutico. Este último debe ser biocompatible y estable en condiciones ambientales, puesto que probablemente este expuesto al ambiente mientras protege la herida, en el caso concreto de este tipo de aplicación. Estos tres elementos, que en sí mismos constituyen sistemas complejos por separado, se han combinado sistemáticamente para alcanzar una relación sinérgica entre ellos de manera que cada uno potencia las cualidades de los otros dos. El constructo resultante se caracterizó demostrando tener propiedades características que se pueden utilizar como parámetro de control durante la fabricación del mismo. Así mismo estudios in vitro del sistema desarrollado señalan que puede ser un buen candidato para el tratamiento de heridas crónicas entre otras patologías que requieran tratamientos localizados. / [CAT] Actualment, una de les majors preocupacions que permanentment llepen l'atenció dels principals sectors de la societat humana és la salut. La ciència mèdica moderna està compromesa no solament amb subministrar tractaments adequats, sinó més aviat oferir solucions efectives i específiques per a cada tipus de malaltia o patologia humana. En aquest sentit, estratègies innovadores com l'enginyeria de teixits o la medicina regenerativa, els sistemes d'alliberament controlat de fàrmacs i les nanomedicines, sorgeixen com a bones alternatives per a abordar situacions difícils de resoldre aplicant els tractaments i estratègies terapèutiques convencionals, com és el cas quan es fa necessari reemplaçar teixits o fins i tot òrgans danyats per algun traumatisme o malaltia. Concretament, el present treball de recerca té per objectiu principal dissenyar un sistema combinat per a l'alliberament controlat, estable i localitzada d'agents terapèutics que seguen capaços d'exercir el seu efecte de forma selectiva sobre la zona que amirita el tractament. Aquest constructe tindrà la versatilitat suficient com per a poder adaptar-se a quasi qualsevol tipus de tractament, des del càncer fins a la regeneració de teixit, sempre que el requisit clau del tractament sega la necessitat de subministrar el tractament de manera localitzada, estable i controlada. Per a efectes de facilitar la compressió i el disseny del sistema es va escollir per a la prova de concepte materials i fàrmacs associats a la regeneració de teixits, com a tractament per a casos de ferides cròniques. El sistema en qüestió està constituït per tres elements principals: 1) El primer element són els conjugats polimèrics d'agents terapèutics que contribuiran a augmentar la selectivitat de l'acció terapèutica del fàrmac, així com també a millora l'estabilitat, biodisponibilitat i biocompatibilitat dels mateixos. En cas que el fàrmac sega hidrofòbic, la conjugació contribueix a augmentar la seua solubilitat en aigua, i en el cas d'usar proteïnes com a agents terapèutics, la conjugació contribueix a disminuir la resposta immunològica del cos incrementant les possibilitat d'èxit del tractament. 2) El segon element són microparticles polimèriques biodegradables, que en aquest cas actuen amb agents d'encapsulació per als conjugats polimèrics, permetent així comptar amb un segon punt de control en la cinètica d'alliberament de l'agent terapèutics. Simultàniament, les microparticles també compleixen un paper de texturitzant del constructe final, adjudicant-li propietats mecànica i fisicoquímiques que contribueixen a millorar la propietats biològiques del material final, com són l'afinitat, l'adhesió i la proliferació cel·lular. 3) El tercer element consisteix en una membrana polimèrica biodegradable nanoporosa feta per electrospinning, que constitueixen el element unificats del sistema, aporta manejabilitat al constructe i és en si mateix el ultimi punt de control en la cinètica d'alliberament de l'agent terapèutic. Aquest últim ha de ser biocompatible i estable en condicions ambientals, ja que probablement aquest exposat a l'ambient mentre protegeix la ferida, en el cas concret d'aquest tipus d'aplicació. Aquests tres elements que en si mateixos constitueixen sistemes complexos per separat, s'han combinat sistemàticament per a aconseguir una relació sinergètica entre ells de manera que cadascun potencia les qualitats dels altres dos. El constructe resultant es va caracteritzar demostrant tenir propietats característiques que es poden utilitzar com a paràmetre de control durant la fabricació del mateix. Així mateix estudis in vitro del sistema desenvolupat assenyalen que pot ser un bon candidat per al tractament de ferides cròniques entre altres patologies que requeriren tractaments localitzats. / Rodríguez Escalona, GDJ. (2016). DEVELOPMENT OF CONTROLLED DRUG DELIVERY SYSTEMS OF POLYMERIC NANOMEDICINES ASSOCIATED TO SCAFFOLDS FOR TISSUE REGENERATION [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/63231 / TESIS