https://hdl.handle.net/10481/64368 Wed, 08 Apr 2026 22:06:46 GMT 2026-04-08T22:06:46Z https://hdl.handle.net/10481/88809 Synthesis and characterization of different sodium hyaluronate nanoparticles to transport large neurotherapheutic molecules through blood brain barrier after stroke. Morales Hernández, María Encarnación Some biological drugs with proven neuroprotective capacity are unable to cross the blood brain barrier (BBB), preventing its use in neuroregenerative diseases such as stroke. The use of nanoparticles as a delivery system to transport large therapeutic molecules to the cerebral parenchyma may be a good option to overcome this lim itation. To achieve this goal, we have designed some polymer nanoparticles (NPs) by two ionic gelation methods of synthesis: external (M1) and internal (M2), both using sodium hyaluronate (SH) as polymer but with differences in the elaboration of their core. Additionally, both SH-NPs were coated with chitosan and glycerol tripalmitin in order to improve their penetration capabilities into cells. The nanoparticles were characterized by size, shape and charge. Then, an experimental approach was carried out in animals submitted to a stroke model, where NPs penetration into the brain was studied and analysed after its systemic administration. All types of NPs assayed were able to cross the BBB and were endocytosed by neurons; however, the SH-NPs obtained by M2 are lightly more efficient in the rate of penetration than those obtained by M1. There were not visible differences between coated and non-coated NPs obtained by both gelation methods. This may be due to the fact that not only the size, shape and charge of NPs, but also its chemical structure influences its cellular capture by endocytic mechanisms https://hdl.handle.net/10481/88809 https://hdl.handle.net/10481/88778 Hyaluronate Nanoparticles as a Delivery System to Carry Neuroglobin to the Brain after Stroke Blanco, Santos; Peralta, Sebastián; Morales Hernández, María Encarnación; Castán, Herminia; Ruiz, María Adolfina Therapies against stroke can restore the blood supply but cannot prevent the ischemic damage nor stimulate the recovery of the infarcted zone. The neuroglobin protein plays an important role in the neuro-regeneration process after stroke; however, the method for its e ective systemic application hasnotbeenidentifiedyet, asneuroglobinisunabletopassthroughtheblood-brainbarrier. Previously, we developed di erent types of sodium hyaluronate nanoparticles, which successfully cross the blood-brain barrier after stroke. In this work, these nanoparticles have been used to carry neuroglobin through the bloodstream to the nerve cells in rats submitted to stroke. We have biosynthesized rat-recombinant neuroglobin and determined the formulation of sodium hyaluronate nanoparticles loaded with neuroglobin, as well as its size and-potential, encapsulation e ciently, in vitro release, and its kinetic of liberation. The results show that the formulation achieved is highly compatible with pharmaceutical use and may act as a delivery system to transport neuroglobin within the blood. We have found that this formulation injected intravenously immediately after stroke reached the damaged cerebral parenchyma at early stages (2 h). Neuroglobin colocalizes with its nanocarriers inside the nerve cells and remains after 24 h of reperfusion. In conclusion, the systemic administration of neuroglobin linked to nanoparticles is a potential neuroprotective drug-delivery strategy after stroke episodes. https://hdl.handle.net/10481/88778 https://hdl.handle.net/10481/88770 Lipid nanoparticles for the transport of drugs like dopamine through the blood-brain barrier Morales Hernández, María Encarnación Diseases and disorders of the nervous system, like Parkinson disease (PD) and others neurodegenerative pathologies are widespread in our society. The arsenal of treatments against these pathologies continues to increase, but in many cases its use is limited. This is due to the blood-brain barrier (BBB), which acts by limiting the penetration of drugs into the brain. To overcome this handicap, in the current research solid lipid nanoparticles (SLNPs) able to encapsulate drugs and to cross the blood-brain barrier have been designed to transport and release these drugs into their targets. These SLNPs were synthesized by a sonication method and high agitation process searching the most adequate physicochemical profile to achieve the objectives set. Today, the most efficient treatment for PD consists of providing the dopamine (DP) that is lost by neurodegeneration; however, the nature of this neurotransmitter prevents its crossing of the BBB. Therefore, DP may be considered as a good candidate to be encapsulated in SLNPs while studying how the loading drug could affect such nanoparticles. Based on these antecedents, in this research, both empty and DP-charged SLNPs were characterized physicochemically. The results obtained indicated a great stability of the nanoparticles loaded with DP when drug was used at 0.2 to 0.05%; these concentrations barely affected its size, polydispersity and ζ-potential, and the SLNPs elaborated in this research were high appropriate to be injected systemically. Finally, empty SLNPs labeled and administered systemically to adult male Wistar rats demonstrate their penetration ability into the brain parenchyma. El periodo de embargo es de 12 meses. Ya transcurridos desde la fecha de publicación https://hdl.handle.net/10481/88770 https://hdl.handle.net/10481/88699 A novel double-layer mucoadhesive Tablet containing probiotic strain for vaginal administration: Design, development and technological evaluation Sánchez, María Teresa; Ruiz, María Adolfina; Castán, Herminia; Morales Hernández, María Encarnación Abstract Vulvovaginal candidosis caused by Candida spp. is the most prevalent vaginal infection in Europe and the second one in EE.UU, so it has become a major female concern. Probiotics bacteria have been proposed as an alternative treatment with the aim of avoiding the adverse effects associated with conventional therapies including antibiotics and other aggressive drugs for the vaginal mucosa and microbiota. The purpose of this work was to design and develop a novel vaginal tablet that contained Lactobacillus spp. bacteria as a treatment against vulvovaginal infections. A total of 21 two-layers vaginal tablets, which contained different polymeric ratios, were proposed. However, formulation F4 (20 mg Na-CMC; 50 mg Carbopol® 934; 20 mg chitosan) was selected as optimal according to its swelling index and dissolution/erosion capability. F4 tablets showed suitable technological properties for vaginal administration as well as mucoadhesion time (24.36 ± 0.88 h) and force (0.0941 N). Disintegration assay in simulated vaginal fluid (SVF, pH 5.5) showed that effervescent layer disappeared in 27.48 ± 0.05 s whilst matrix layer was totally gelled in 1 h. Two different release profiles were achieved; on the one hand, a promptly release due to the dissolution of both effervescent layer and matrix layer's surface (1.10 × 108 CFU/g), on the second hand, a prolonged released of the remaining bacteria until 24 h (5.48 × 107 CFU/g). For stability and storage study, it was found that bacteria viability was constant until 90 days in both ways of storage, in a desiccator and at room temperature, with a final dosage of 108 CFU/g which was considered appropriate for vaginal therapy (108–1010 CFU/g). https://hdl.handle.net/10481/88699 https://hdl.handle.net/10481/64517 Improvement of mesoporous silica nanoparticles: a new approach in the administration of NSAIDs Ortega, Elena; Ruiz Martínez, Adolfina; Peralta, Sebastián; Russo, Gabriella; Morales Hernández, María Encarnación Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute a heterogeneous group of compounds that exhibit analgesic, anti-inflammatory and antipyretic activity. However, the GI damage produced by NSAIDs has been widely studied. Thus, the aim of the present study was the development of mesoporous silica nanoparticles in order to increase the capacity of drug transport, emphasizing those with low solubility such as NSAIDs. The morphology and structure characteristics of the synthesized nanoparticles were studied by transmission electron microscopy (TEM), besides, its particle size, surface charge, specific area and cell viability will be determined. The analytical application of mesoporous silica nanoparticles as ibuprofen carrier was also evaluated by measuring their drug loading characteristics and release behavior. The results showed that the synthesized NPs had efficient physicochemical characteristics, high EE%, low toxicity, and controlled ibuprofen release. https://hdl.handle.net/10481/64517