The master's thesis focuses on preparation of blown films from polylactid acid (PLA) which was blended with selected polyesteres – poly(butylene adipate-co-terephtalate) (PBAT), polycaprolactone (PCL) and polybutylene succinate (PBS) – and thermoplastic starch (TPS) in amount of 30% in order to soften PLA films. The influence of the aditives on static and mechanical tensile properties, on structure, morphology and thermal properties of the films was determined and the obtained parameters were compared to properties of films prepared from neat PLA and high density polyethylene (HDPE). The results showed that the additives increased crystalinity of PLA and thus significantly influenced the properties of the films. In contrast to the film from neat PLA, softening in terms of lowering glass transition temperature occured only by adding PBS and TPS, in terms of increasing ductility only by adding PBAT. All PLA films showed nearly constant elastic modulus up to the beginning of glass transition enabling their potential application till 50 °C. Preparation of the film with TPS was problematic and the film showed the worst mechanical properties. Preparation of other films was without any problems. The most promising additive from the tested ones was PBAT which showed comparable mechanical properties as the film from HDPE.

This diploma thesis is focused on preparation of liposome by relatively new method called nanofluidisation. This method allows the controlled preparation of small unilamellar liposomes in one step. In my thesis I was dealing with optimalization of liposomes preparation which carry hydrophobic cytostatics using this method. Cytotoxic effect of liposomes carrying hydrophobic cytostatics in vitro on cell lines A549 and MCF-7 was determined. In cytotoxicyty test I compared the effect of hydrophobic cytostatics (paclitaxel and derivates of vitamin E specifically alfa-Tos, alfa-TEA) that were incorporated into liposomes prepared via nanofluidisation method and lipid film hydration method. Moreover, a technology of lyophilisation in the presence of cryoprotectants for preparation of liposomes using the method of nanofluidisation was developed.

In this thesis, the incorporation of drug loaded mesoporous magnesium carbonate as an excipient for the additive manufacturing of oral tablets by fused deposition modeling was investigated. Cinnarizine, a BCS class II drug, was loaded into the pores of the mesoporous material via a soaking method, corresponding to a drug loading of 8.68 wt%. DSC measurements on the loaded material suggested that the drug was partially crystallized after incorporation, meanwhile the XRD diffractogram implied that the drug was in a state lacking long range order. The drug loaded material was combined with two pharmaceutical polymers, Aquasolve LG and Klucel ELF, and extruded into filaments with a single screw extruder. Filaments of Klucel ELF and drug loaded Upsalite (30:70 wt% ratio) were successfully implemented for the printing oral tablets, in contrast to the Aquasolve LG based filaments which were difficult to print due to thickness variations and non-uniform material distributions. The drug content obtained by TGA suggested drug loadings of 7.71 wt% and 2.23 wt% in the drug loaded Upsalite and tablets respectively. Dissolution studies using an USP II apparatus showed a slower API-release from the tablets in comparison to the crystalline drug, most probably due to slow diffusion of drug species through the polymeric matrix. For future studies, pharmaceutical polymers with higher aqueous solubility should be investigated in order to thoroughly examine the potential of utilizing the immediate release property of Upsalite.

The hypothalamus-pituitary-adrenal (HPA) axis is activated in response to inflammation leading to increased production of anti-inflammatory glucocorticoids by the adrenal cortex, thereby representing an endogenous feedback loop. However, severe inflammation reduces the responsiveness of the adrenal gland to adrenocorticotropic hormone (ACTH), although the underlying mechanisms are poorly understood. Here, we show by transcriptomic, proteomic, and metabolomic analyses that LPS-induced systemic inflammation triggers profound metabolic changes in steroidogenic adrenocortical cells, including downregulation of the TCA cycle and oxidative phosphorylation, in mice. Inflammation disrupts the TCA cycle at the level of succinate dehydrogenase (SDH), leading to succinate accumulation and disturbed steroidogenesis. Mechanistically, IL-1β reduces SDHB expression through upregulation of DNA methyltransferase 1 (DNMT1) and methylation of the SDHB promoter. Consequently, increased succinate levels impair oxidative phosphorylation and ATP synthesis and enhance ROS production, leading to reduced steroidogenesis. Together, we demonstrate that the IL-1β-DNMT1-SDHB-succinate axis disrupts steroidogenesis. Our findings not only provide a mechanistic explanation for adrenal dysfunction in severe inflammation, but also offer a potential target for therapeutic intervention.

Applications of Hot Melt Extrusion (HME) in pharmaceuticals have become increasingly popular over the years but nonetheless a few obstacles still remain before wide scale implementation. In many instances these improvements are related to both processing and product performance. It is observed that HME process optimisation is majorly focused on the active pharmaceutical ingredient's (API) properties. Characterising polymeric properties for their suitability in HME should be equally studied since the impact of excipients on both product and process performance is just as vital. In this work, two well-established cellulose ester derivatives: Hydroxy Propyl Methyl Cellulose Acetate Succinate (HPMCAS) and Hydroxy Propyl Methyl Cellulose Phthalate (HPMCP) are studied for their HME suitability. Their thermal, thermodynamic, rheological, thermo-chemical and degradation kinetic properties were evaluated with model plasticisers and APIs. It was found the thermal properties of HPMCP are severely compromised whereas HPMCAS is more stable in the processing zone of 150 to 200 °C. Thermodynamic properties revealed that both polymers share an important solubility parameter range (20-30 MPa P1/2P) where the majority of plasticisers and BCS class II APIs lie. Thus, greater miscibility/solubility can be expected. Further, the processability of these two polymers investigated by rheometric measurements showed HPMCAS possesses better flow properties than HPMCP because HPMCP forms a weak network of chain interactions at a molecular level. However, adding plasticisers such as PEG and TEC the flow properties of HPMCP can be tailored. The study also showed that plasticisers have a major influence on thermo-chemical and kinetic properties of polymers. For instance, PEG reduced polymer degradation with reversal in kinetic parameters whereas blends of CA produced detrimental effects and increased polymer degradation with reduction in onset degradation temperatures. Further, both polymers are observed to be chemically reactive with the APIs containing free -OH, -SOR2RN- and -NH2 groups. Finally, these properties prove that suitability of HPMCP is highly debated for HME and demands great care in use while that of HPMCAS is relatively better than HPMCP in many instances.

Additives, incorporated in film coating formulations, and their process parameters are generally selected using a trial-and-error approach. However, coating problems and defects, especially those associated with aqueous coating systems, indicate the necessity of embracing a quality-by-design approach to identify the optimum coating parameters. In this study, the feasibility of using thermal and rheological measurements to help evaluate and design novel coating formulations has been investigated. Hydroxypropyl methylcellulose acetate succinate (HPMCAS), an enteric coating polymer, was used as the film forming polymer. Differential Scanning Calorimetry (DSC), Dynamic Mechanical Analysis (DMA), and Parallel Plate Shear Rheometery (PPSR) were used to evaluate the effect of different plasticisers on the performance of HPMCAS. The results illustrate that, for identical formulations, the DSC and DMA methods yielded up to 40% differences in glass transition temperature (Tg) values. Moreover, Tg measured using loss modulus signals were always 20-30 oC less than those measured using tan delta results in DMA testing. Absolute and relative Tg values can significantly vary depending on the geometry of the samples, clamp size, temperature ramping rate and the frequency of the oscillations. Complex viscosity data for different formulations demonstrated a variable shear thinning behaviour and a Tg independent ranking. It is, therefore, insufficient to rely purely on Tg values to determine the relative performance of additives. In addition, complex viscosity results, obtained using both the DMA and PPSR techniques at similar temperatures, are shown to be comparable. The results from both techniques were therefore used to produce continuous master curves for the HPMCAS formulations. Additionally, step strain tests showed that HPMCAS chains do not fully III disentangle after 105 seconds as predicted by the Maxwell model. Finally, in situ aqueous-based coating experiments proved that mixtures of triethyl acetyl citrate and acetylated monoglyceride (TEAC/AMG), even without cooling of the suspension, do not cause blocking of the spray nozzle whereas triethyl citrate (TEC) based formulae did. TEAC (alone or in a combination with AMG) exhibits superior wettability to HPMCAS than TEC/AMG formulations and can be used to enhance the efficiency and film quality of the dry coating process.

L'adaptation à l'environnement est essentielle à la survie cellulaire et des organismes en général. La capacité d'adaptation aux variations en oxygène repose sur des mécanismes de détection de l'hypoxie et une capacité à répondre en amorçant un programme d'angiogenèse. Bien que la contribution du facteur induit par l'hypoxie (HIF) est bien définie dans l'induction d'une telle réponse, d'autres mécanismes sont susceptibles d'être impliqués. Dans cette optique, les études démontrant l'influence du métabolisme énergétique sur le développement vasculaire sont de plus en plus nombreuses. L'un de ces composés, le succinate, a récemment été démontré comme étant le ligand du GPR91, un récepteur couplé aux protéines G. Parmi les différents rôles attribués à ce récepteur, notre laboratoire s'intéressa aux rôles du GPR91 dans la revascularisation observée suite à des situations d'hypoxie dont ceux affectant la rétine. Il existe cependant d'autres conditions pour lesquelles une revascularisation serait bénéfique notamment suite à un stress hypoxique-ischémique cérébral. Nos travaux ont pour objectifs de mieux comprendre le rôle et le fonctionnement de ce récepteur durant le développement et dans le cadre de pathologies affectant la formation de vaisseaux sanguins. Dans un premier temps, nous avons déterminé le rôle du GPR91 dans la guérison suite à un stress hypoxique-ischémique cérébral chez le nouveau-né. Nous montrons que ce récepteur est exprimé dans le cerveau et en utilisant des souris n'exprimant pas le GPR91, nous démontrons que dans un modèle d'hypoxie-ischémie cérébrale néonatal l'angiogenèse prenant place au cours de la phase de guérison dépend largement du récepteur. L'injection intracérébrale de succinate induit également l'expression de nombreux facteurs proangiogéniques et les résultats suggèrent que le GPR91 contrôle la production de ces facteurs. De plus, l'injection de ce métabolite avant le modèle d'hypoxie-ischémie réduit substantiellement la taille de l'infarctus. In vitro, des essaies de transcription génique démontrent qu'à la fois les neurones et les astrocytes répondent au succinate en induisant l'expression de facteurs bénéfiques à la revascularisation. En considérant le rôle physiologique important du GPR91, une seconde étude a été entreprise afin de comprendre les déterminants moléculaires régissant son activité. Bien que la localisation subcellulaire des RCPG ait traditionnellement été considérée comme étant la membrane plasmique, un nombre de publications indique la présence de ces récepteurs à l'intérieur de la cellule. En effet, tel qu'observé par microscopie confocale, le récepteur colocalise avec plusieurs marqueurs du réticulum endoplasmique, que celui-ci soit exprimé de façon endogène ou transfecté transitoirement. De plus, l’activation des gènes par stimulation avec le succinate est fortement affectée en présence d'inhibiteur du transport d'acides organiques. Nous montrons que le profil de facteurs angiogéniques est influencé selon la localisation ce qui affecte directement l'organisation du réseau tubulaire ex vivo. Finalement, nous avons identifié une région conservée du GPR91 qui agit de signal de rétention. De plus, nous avons découvert l'effet de l'hypoxie sur la localisation. Ces travaux confirment le rôle de régulateur maître de l'angiogenèse du GPR91 lors d'accumulation de succinate en condition hypoxique et démontrent pour la première fois l'existence, et l'importance, d'un récepteur intracellulaire activé par un intermédiaire du métabolisme. Ces données pavent donc la voie à une nouvelle avenue de traitement ciblant GPR91 dans des pathologies hypoxiques ischémiques cérébrales et soulèvent l'importance de tenir compte de la localisation subcellulaire de la cible dans le processus de découverte du médicament. / The ability to adapt to the changing environment is essential for the survival of cells and organisms in general. The capacity to adjust to variations in oxygen content not only relies on the ability to sense hypoxia but also depends the time required to induce an angiogenic process. Notwithstanding the important contribution of the hypoxia inducible factor (HIF) in this response, other mechanisms are likely to be involved. Studies that have demonstrated the influence of metabolic compounds on vascular development are increasingly abundant. One of those compounds, succinate, has recently been indentified as the ligand of GPR91, a G-protein-coupled receptor. Amongst the roles of this receptor, our group has been interested in determining its contribution in revascularisation observed following hypoxic events in the retina. Other pathological conditions could benefit from the contribution of GPR91 including cerebral hypoxia-ischemia. Our objective is to better understand the role of this receptor during development and in pathological conditions affecting blood vessel formation. We first, determined the role of GPR91 in revascularisation following cerebral hypoxia-ischemia in the newborn. We show the expression of the receptor in the cerebral cortex. Using mice devoid of GPR91, we demonstrate that angiogenesis normally taking place during the recovery phase is largely dependent upon GPR91. Intracerebral injection of succinate induces the expression of several proangiogenic growth factors by activating GPR91. Furthermore, injection of succinate before cerebral H-I model substantially reduces the infarct size. In vitro, gene transcription shows that neurons and astrocytes respond to succinate and produce factors beneficial to revascularisation. Considering the important physiological role of GPR91, a second study was initiated to better determine the molecular determinants controlling the receptor's activity. The plasma membrane has classically been considered the typical GPCR's location of action but several new publications indicate the presence of such receptors within the cell. We observe, by confocal microscopy, the colocalisation of GPR91 (endogenous or transfected) with several marker of the endoplasmic reticulum. In addition, the gene induction observed when stimulated with succinate is severely affected in presence of the compound probenicid, an organic anion transporter inhibitor. We also demonstrate that the profile of genes expressed is largely dependent on the localisation of the receptor and consequently affects the organization of the tubular network ex vivo. Finally, we have identified a conserved region of GPR91 that acts as a retention signal. Lastly, we have uncovered the consequence of hypoxia affecting the post-translational modification of GPR91 and its change in location from the ER to the plasma membrane. This work confirms the role of GPR91 as a master regulator of angiogenesis in situations where succinate accumulates and demonstrated for the first time the existence, and importance, of an intracellular receptor activated by a metabolic intermediate. These results pave the way for future treatment targeting GPR91 in cerebral hypoxic ischemic pathologies and demonstrate the importance of taking into account the subcellular localisation in the drug discovery process.

- 8 - ABSTRACT (EN) The thesis is submitted as a commented set of reviewed publications documenting and depicting the possibilities of mass spectrometry in the field of chemical, biological and pharmaceutical research; namely for the purposes of structure elucidation of selected organometallic complexes, analyses of drugs and their metabolites, monitoring of important biological markers. In course of experimental work, the following objectives were studied and solved:  Proposal and realization of micro-scale preparation of selected rhenium complexes with aromatic ligands, utilizing tetrabutyammonium tetrachlorooxorhenate as a starting material; preparation and structure characterization of oxorhenium(V) complexes with 1,2-dihydroxybenzene, 1,2,3-trihydroxybenzene, and 2,3- dihydroxynaphtalene as ligands by means of ESI/MS, APPI/MS and LDI-MS; ESI/MS and UV/Vis study of kinetic behavior of complexes arising from the reaction of tetrabutylamonnium tetrachlooxorhenate with pyrogallol and catechol as ligands. Special aim was devoted to the study of subsequent chemical transformation of primarily formed Re(V) complexes; structure characterization of selected ferrocene complexes with copper, gold and silver by means of ESI/MS.  Proposal of methodology of structure characterization and quantification of the...

Tesis por compendio / [ES] Esta tesis doctoral tuvo como objetivo principal el estudio, desarrollo y caracterización de nuevos materiales poliméricos mediante el uso de diferentes matrices poliméricas de origen natural y biodegradables, así como también de aditivos naturales y residuos agroindustriales, todo ello con la finalidad de obtener biopolímeros útiles en el sector envase y embalaje. Una de las matrices seleccionadas para su uso fue el bio-poli(etileno) de alta densidad (bio-HDPE). El bio-HDPE es un material que se puede obtener a partir de fuentes naturales renovables. Sin embargo, no es susceptible de biodegradación, es por ello que se planteó la adición de cargas y aditivos naturales a la matriz polimérica, con la finalidad de obtener nuevos materiales en los que el uso de estas cargas permita una disminución de la cantidad de matriz polimérica necesaria, además de la posibilidad de proporcionarle al polímero nuevas características y propiedades gracias a los principios activos (fenoles, flavonoides, etc.) que poseen en su estructura. Las cargas utilizadas fueron por un lado harina de piel de caqui (PPF) y, por otro, lignina Kraft (KL). Teniendo en consideración la baja compatibilidad que existe entre la matriz polimérica y las cargas naturales debido básicamente a su inherente hidrofobicidad e hidrofilicidad, respectivamente, se propuso el uso de diferentes técnicas de compatibilización. Adicionalmente, teniendo en consideración que las cargas de origen natural tienen diferentes principios activos en su estructura, algunos de ellos con capacidad antioxidante se analizó su efecto en las propiedades térmicas de las muestras con (PPF). El estudio continuó con la utilización de poli(ésteres) como el poli(ácido láctico) (PLA) y poli(butilén succinato) (PBS). En el caso del PLA se buscó mejorar la fragilidad propia del material mediante la adición de un oligómero de ácido láctico (OLA) como agente plastificante y se obtuvo que a mayor cantidad de plastificante la ductilidad del PLA incrementaba. Adicionalmente, con el fin de enfocar el material al uso en el sector de envase y embalaje, se buscó mejorar sus propiedades barrera mediante la incorporación de nanomateriales, concretamente nanotubos de haloisita (HNTs). En el caso del PBS, si bien es un material biodegradable, su obtención aún depende de fuentes petroquímicas total o parcialmente, además que su producción implica un alto costo, por tanto, es importante la búsqueda de alternativas que permitan combinarlo con recursos naturales, para lograr un material menos costoso y más respetuoso con el medio ambiente. Es por ello que se consideró el uso de harina de cáscara de pistacho (SPF) como carga natural. Una última fase de la tesis consistió en el aprovechamiento de los residuos agroindustriales, mediante la extracción de algunos de sus biopolímeros, entre ellos proteínas, lignina y nanocristales de celulosa (CNC), los cuales luego fueron combinados, con la finalidad de obtener películas para su posible uso en el sector envase y embalaje. La lignina y los CNC fueron obtenidos a partir de las piñas de pino y utilizados como materiales de refuerzo para la matriz de proteína procedente del haba. La incorporación de dichos compuestos en la película de proteína dio lugar a un incremento en las propiedades mecánicas en términos de módulo de Young y resistencia a la tracción, además tuvo repercusión en las propiedades barrera, reduciendo la permeabilidad al vapor de agua y al oxígeno. En las muestras con CNC se observó un incremento en la hidrofobicidad de las películas obtenidas, relacionado también con la disminución en el contenido de humedad y la solubilidad reportados. Por tanto, de manera general se puede decir que con el trabajo desarrollado se pudieron obtener materiales biopoliméricos con características prometedoras para su aplicación en el sector envase y embalaje, planteando con ello opciones al uso de materiales poliméricos derivados del petróleo. / [CAT] Aquesta tesi doctoral va tindre com a objectiu principal l'estudi, desenvolupament i caracterització de nous materials polimèrics mitjançant l'ús de diferents matrius polimèriques d'origen natural i biodegradables, així com també d'additius naturals i residus agroindustrials, tot això amb la finalitat d'obtindre biopolímers útils en el sector envase i embalatge. Una de les matrius seleccionades per al seu ús va ser el bio-poli(etilé) d'alta densitat (bio-HDPE). El bio-HDPE és un material que es pot obtindre a partir de fonts naturals renovables. No obstant això, no és susceptible de biodegradació, és per això que es va plantejar l'addició de càrregues i additius naturals a la matriu polimèrica, a més de la possibilitat de proporcionar-li al polímer noves característiques i propietats gràcies als principis actius (fenols, flavonoides, etc.) que posseeixen en la seua estructura. Les càrregues utilitzades van ser d'una banda farina de pell de caqui (PPF) i, per un altre, lignina Kraft (KL). Tenint en consideració la baixa compatibilitat que existeix entre la matriu polimèrica i les càrregues naturals degut bàsicament a la seua inherent hidrofobicitat i hidrofilicitat, respectivament, es va proposar l'ús de diferents tècniques de compatibilització. Addicionalment, tenint en consideració que les càrregues d'origen natural tenen diferents principis actius en la seua estructura, alguns d'ells amb capacitat antioxidant, es va analitzar el seu efecte en les propietats tèrmiques de les mostres mostres amb (PPF). L'estudi va continuar amb la utilització de polièsters com el poli(àcid làctic) (PLA) i poli(butilén succinat) (PBS). En el cas del PLA es va buscar millorar la fragilitat pròpia del material mitjançant l'addició d'un oligòmer d'àcid làctic (ONA) com a agent plastificant i es va obtindre que a major quantitat de plastificant la ductilitat del PLA incrementava. Addicionalment, amb la fi que enfocar el material a l'ús en el sector d'envàs i embalatge, es va buscar millorar les seues propietats barrera mitjançant la incorporació de nanomaterials, concretament nanotubs d'haloisita (HNTs). En el cas del PBS, si bé és un material biodegradable, la seua obtenció encara depén de fonts petroquímiques totalment o parcialment, a més que la seua producció implica un alt cost, per tant, és important la cerca d'alternatives que permeten combinar-lo amb recursos naturals, per a aconseguir un material menys costós i més respectuós amb el medi ambient. És per això que es va considerar l'ús de farina de corfa de pistatxo (SPF) com a càrrega natural. Una última fase de la tesi va consistir en l'aprofitament dels residus agroindustrials, mitjançant l'extracció d'alguns dels seus biopolímers, entre ells proteïnes, lignina i nanocristals de cel·lulosa (CNC), els quals després van ser combinats, amb la finalitat d'obtindre pel·lícules per al seu possible ús en el sector envase i embalatge. La lignina i els CNC van ser obtinguts a partir de les pinyes de pi i utilitzats com a materials de reforç per a la matriu de proteïna procedent de la fava. La incorporació d'aquests compostos en la pel·lícula de proteïna va donar lloc a un increment en les propietats mecàniques en termes de mòdul de Young i resistència a la tracció, a més va tindre repercussió en les propietats barrera, reduint la permeabilitat al vapor d'aigua i a l'oxigen. En les mostres amb CNC es va observar un increment en la hidrofobicitat de les pel·lícules obtingudes, relacionat també amb la disminució en el contingut d'humitat i la solubilitat reportats. Per tant, de manera general es pot dir que amb el treball desenvolupat es van poder obtindre materials biopolimerics amb característiques prometedores per a la seua aplicació en el sector envase i embalatge, plantejant amb això opcions a l'ús de materials polimèrics derivats del petroli. / [EN] The main objective of this doctoral thesis was the study, development, and characterization of new polymeric materials using different polymeric matrices of natural origin and biodegradables, as well as natural additives and agro-industrial wastes, all with the aim of obtaining biopolymers useful in the packaging sector. One of the matrices selected for use was high-density bio-poly(ethylene) (bio-HDPE). Bio-HDPE is a material that can be obtained from natural renewable sources. However, it is not susceptible to biodegradation, which is why the addition of fillers and natural additives to the polymeric matrix was proposed. All of this with the purpose of obtaining new materials in which the use of these fillers allows a decrease in the amount of polymeric matrix required. In addition to the possibility of providing the polymer with new characteristics and properties thanks to the active principles (phenols, flavonoids, etc.) contained in its structure. The fillers used were persimmon peel flour (PPF) and Kraft lignin (KL). Considering the low compatibility between the polymeric matrix and the natural fillers, basically due to their inherent hydrophobicity and hydrophilicity, respectively, the use of different compatibilization techniques was proposed. In addition, taking into consideration that the fillers of natural origin have different active principles in their structure, some of them with antioxidant capacity, their effect on the thermal properties of the samples with (PPF) was analyzed. The study continued with the use of polyesters such as poly(lactic acid) (PLA) and poly(butylene succinate) (PBS). In the case of PLA, the aim was to improve the fragility of the material by adding a lactic acid oligomer (OLA) as a plasticizing agent. It was found that the greater the amount of plasticizer, the higher the ductility of PLA. Additionally, in order to focus the material for use in the packaging sector, it was sought to improve its barrier properties by incorporating nanomaterials, specifically halloysite nanotubes (HNTs). In the case of PBS, although it is a biodegradable material, its obtention still depends totally or partially on petrochemical sources, and its production implies a high cost; therefore, it is crucial to look for alternatives that allow combining it with natural resources, in order to achieve a less expensive and more environmentally friendly material. For this reason, pistachio shell flour (SPF) was considered as a natural filler. A final phase of the thesis consisted of using natural resources and agro-industrial wastes by extracting some of their biopolymers, including proteins, lignin, and cellulose nanocrystals (CNC), which were then combined in order to obtain films for possible use in the packaging sector. Lignin and CNCs were obtained from pine cones and used as reinforcing materials for the protein matrix obtained from faba beans. Incorporating these compounds in the protein film resulted increased mechanical properties in terms of Young's modulus and tensile strength, and also impacted on the barrier properties, reducing the permeability to water vapor and oxygen. In the CNC samples, an increase in the film's hydrophobicity was observed, which is also related to the decrease in moisture content and solubility reported. Therefore, in general, it is possible to say that with the work developed, it was possible to obtain biopolymeric materials with promising characteristics for their application in the packaging sector, thus offering options for the use of petroleum-derived polymeric materials. / This research is a part of the grant PID2020-116496RB-C22 funded by MICINN/AEI/10.13039/501100011033, and the projects AICO/2021/025 and CIGE/2021/094 funded by Generalitat Valenciana-GVA. Funding for open access charge: Universitat Politècnica de València. The authors want to thank the Spanish Ministry of Science and Innovation, gthe Ministry of Science and Innovation (MICINN) [MAT2017-84909-C2-2-R]. for funding this research. S. Rojas-Lema is a recipient of a Santiago Grisolia grant from Generalitat Valenciana (GVA) (GRISOLIAP/2019/132). / Rojas Lema, SP. (2022). Desarrollo y optimización de nuevas formulaciones de biopolímeros con principios activos para aplicaciones en el sector envase-embalaje [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/191458 / Compendio