DSpace Coleção:http://repositorio.ufc.br/handle/riufc/1842024-03-29T08:14:02Z2024-03-29T08:14:02ZDesenvolvimento e caracterização de nanodispersões líquido-cristalinas contendo AICIPc para uso em terapia fotodinâmica em linhagem celular de câncer de peleBorges, Márcia Hermínia Pinheirohttp://repositorio.ufc.br/handle/riufc/765672024-03-14T16:36:56Z2024-01-01T00:00:00ZTítulo: Desenvolvimento e caracterização de nanodispersões líquido-cristalinas contendo AICIPc para uso em terapia fotodinâmica em linhagem celular de câncer de pele
Autor(es): Borges, Márcia Hermínia Pinheiro
Abstract: Non-melanoma skin cancer is one of the most common tumors in the world. Photodynamic
therapy (PDT) is currently a non-invasive therapeutic option for the treatment of skin
cancer and skin cancer precursor lesions. Chloro-aluminum phthalocyanine (AlClPc) is a
second-generation photosensitizer that has been studied for application in PDT. AlClPc is
a hydrophobic molecule and tends to self-aggregate in aqueous and biological
environments, which impairs its therapeutic action. Encapsulation in nanocarriers can
contribute to the maintenance of the monomeric structure and consequently improve its
effectiveness in biological environments. In this sense, the association of nanotechnology
with AlClPc, through encapsulation in nanocarriers, can contribute to its stability and
effectiveness. Liquid crystalline nanodispersions (NLC) have been widely studied as drug
nanocarriers, due to their unique nanostructure that presents desired characteristics for drug
administration through various routes. In this work, NLCs based on oleic acid (AO), Phosal
75SA®, containing or not D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) in
PBS buffer containing poloxamer P407 (P407), with subsequent incorporation of AlClPc
into the Selected NLC (NLC-AlClPc). The obtained NLC-AlClPc was characterized,
showing a nanometric size (152.3 ± 1.93 nm), PDI and encapsulation efficiency (EE%) of
0.231 ± 0.009 and 70.26 ± 3.87%, respectively, and stability for 30 days. NLC-AlClPc
showed morphology compatible with a hexagonal phase in polarized light microscopy,
which was confirmed in small-angle X-ray diffraction (SAXS). In the in vitro skin
penetration test, NLC-AlClPc showed better penetration into the deep layers of the skin
than the AlClPc-propylene glycol control. Cytotoxicity and phototoxicity at 630nm were
also evaluated in two cell lines using the MTT method. NLC-AlClPc showed greater
phototoxicity in the A431 tumor line than free AlClPc and greater phototoxicity in A431 in
relation to the L929 fibroblast cell line. The proposed formulation developed, in addition
to being innovative, presented satisfactory results in the characterizations carried out, as
well as being able to improve, in vitro, the skin penetration of AlClPc and the
photodynamic action in tumor lineage.
Tipo: Dissertação2024-01-01T00:00:00ZAnálise clínica e econômica das recomendações farmacêuticas em unidade de terapia intensivaHolanda, Ângela Nadyla Martinshttp://repositorio.ufc.br/handle/riufc/763992024-03-06T14:31:42Z2019-01-01T00:00:00ZTítulo: Análise clínica e econômica das recomendações farmacêuticas em unidade de terapia intensiva
Autor(es): Holanda, Ângela Nadyla Martins
Abstract: Intensive care is a highly critical sector within hospital units, which has as its main feature the
complexity of the treatments provided to patients. The optimization of drug use and the
development of pharmacotherapeutic follow-ups increase the quality of care, safety, and also
reduce costs, rationalizing the services provided. In this sense, this research aimed to analyze
the clinical and economic impacts of pharmaceutical recommendations made in units.
intensive care unit of a university hospital in the state of Ceará. The descriptive retrospective
study involved patients admitted to the Intensive Care Unit (ICU), in 2016 and 2017, who had
their pharmacotherapeutic follow-ups documented in a specific instrument, enabling the
clinical analysis of pharmaceutical recommendations. Data collection took place from January
to June 2019. In turn, for the economic evaluation of the pharmaceutical recommendations,
the values of drug acquisition by the institution were analyzed through consultation with its
own system. Pharmaceutical recommendations were analyzed and classified into Increased
Effectiveness, Directly Reduced Costs with Drug Use, and Avoided Costs, when it was
possible to identify that an adverse event was prevented. Data were entered into the Excel
spreadsheet and analyzed by simple statistics. 1,492 recommendations were identified and
analyzed, with 1,456 accepted. In 2016, 525 RF were evaluated, 298 of which being increased
efficiency, 152 reduced costs and 75 avoided costs. In 2017, 931 RF were analyzed, with 539
increasing efficiency, 288 reduced costs and 113 avoided costs. Total costs due to reduced
costs were R $ 67,922.14 and avoided costs were R $ 266,839.26 reais,
resulting in an estimated final value of R $ 334,761.40. It is concluded that the clinical and
financial impact through intensive care pharmaceutical services are relevant and related to the
increased safety and cost reduction of pharmacotherapy of critically ill patients.
Tipo: Dissertação2019-01-01T00:00:00ZEstudo químico e farmacológico do extrato hidroalcoólico do cogumelo Agaricus blazei Murill e seu emprego no desenvolvimento de scaffolds para o reparo tecidualCampelo, Matheus da Silvahttp://repositorio.ufc.br/handle/riufc/763352024-02-29T12:38:04Z2023-01-01T00:00:00ZTítulo: Estudo químico e farmacológico do extrato hidroalcoólico do cogumelo Agaricus blazei Murill e seu emprego no desenvolvimento de scaffolds para o reparo tecidual
Autor(es): Campelo, Matheus da Silva
Abstract: The present work aimed to characterize the chemical profile and pharmacological
potential of the hydroalcoholic extract from Agaricus blazei Murill mushroom (EAb) and
its bioactive compounds (mannitol and polysaccharides), as well as to employ it in
scaffolds for tissue repair. The EAb was prepared by dynamic maceration from a
hydroethanolic mixture (70%, v v-1) as solvent, while the polysaccharides (PAb) were
isolated by hot water methodology. The chemical composition of EAb was studied by
Two-Dimensional Nuclear Magnetic Resonance (2D NMR) and Gas ChromatographyMass Spectrometry (GC-MS). In addition, its antioxidant activity was determined by
chemical methods, as well as the content of reducing sugars. The PAbs were characterized
by ¹H and ¹³C NMR and High Performance Liquid Chromatography (HPLC). The safety
and efficacy of EAb, mannitol and PAb were studied using red blood cells, platelets and
human neutrophils. The polymer matrix of the scaffolds consisted of alginate and
carboxymethylcellulose reinforced with starch nanocrystals (SNCs). SNCs were
synthesized by acid hydrolysis and characterized based on their morphology and colloidal
properties. The structural, thermal, morphological and mechanical properties of the
scaffolds were also evaluated. Through the analysis of 2D NMR, GC-MS and
quantification of reducing sugars, it was found that the chemical profile of the EAb
consists mostly of sugars and amino acids that together represent more than 80% of the
chemical variety of this complex matrix. In addition, EAb showed significant antioxidant
activity, especially in the superoxide anion scavenging assay (IC50 < 1 µg mL-1). The
analysis of the monosaccharide composition of PAb by HPLC indicated glucose as the
major monosaccharide in a content of 76.36%. EAb, mannitol and PAb showed low
cytotoxicity against red blood cells, platelets and human neutrophils in a concentration
range that varied from 1 to 200 µg mL-1, parameters that were studied through the
hemolysis index, evaluation of membrane integrity and cell viability. At the same time,
EAb demonstrated potential in vitro anti-inflammatory activity against the reduction of
myeloperoxidase release by PMA-stimulated neutrophils (Log CE50 = 1.35 µg mL-1) with
better results than those obtained for indomethacin. Mannitol significantly reduced (p <
0.05) the release of MPO only at the highest concentration (80 µg mL-1), suggesting the
existence of an additive effect between this compound and the others present in the EAb.
On the other hand, PAbs showed a modulating effect on MPO release in a concentrationdependent manner, showing an anti-inflammatory effect at lower concentrations (1-10 µg
mL-1) and pro-inflammatory at higher concentrations (100-200 µg mL-1). The SNCs had
a hydrodynamic diameter lower than 200 nm and a zeta potential higher than the modulus
of 20 mV. Furthermore, in the microscopic analysis, particles with even smaller diameter
(~100 nm) and oblong morphology were observed. Scaffolds characterization showed
that the use of EAb and SNCs increases the porosity, thermal stability and absorption
capacity of the formulations, which may be due to intermolecular interactions between
the chemical constituents of the EAb and the polymeric matrix, which was evidenced by
spectroscopic techniques. Therefore, with these data, we can suggest that the
incorporation of EAb in composite scaffolds based on
alginate/carboxymethylcellulose/starch nanocrystals is a promising strategy for the
development of new formulations with potential for tissue repair.
Tipo: Dissertação2023-01-01T00:00:00ZAção antimicrobiana de análogos da dinoponeratoxina M- PONTXDq3a sobre cepas de Staphylococcus aureusSilva Júnior, Pedro Nonato dahttp://repositorio.ufc.br/handle/riufc/762682024-02-26T16:38:05Z2024-01-01T00:00:00ZTítulo: Ação antimicrobiana de análogos da dinoponeratoxina M- PONTXDq3a sobre cepas de Staphylococcus aureus
Autor(es): Silva Júnior, Pedro Nonato da
Abstract: The growing incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections is
associated with increased mortality rates, generating the interest on the developing of
antimicrobial peptides (AMP), such those from the giant ant Dinoponera quadriceps. In order
to improve the net positive charge and the antibacterial activity of the AMP, amino acids with
positive side chain single substituted analogues have been proposed, mainly arginine or lysine.
Thus, the present work aims to study the antimicrobial activity of the analogues of M-PONTX-
Dq3a, a 23 amino acid AMP identified in the D. quadriceps venom. M-PONTX-Dq3a[1-15], a
fragment containing the 15 central amino acids, and eight derivatives single arginine or lysine
substituted analogues were proposed. After, the antimicrobial activity of these peptides was
tested against Staphylococcus aureus ATCC 6538P (MSSA) and ATCC 33591 (MRSA) strains.
Minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) were
determined, as well the minimum biofilm inhibitory concentration (MBIC). Membrane
permeability was assessed using the Crystal violet (CV) assay and flow cytometry using with
propidium iodide. The effect of exposure time on microbial viability (Time-Kill) was evaluated.
Ultrastructural alterations were evaluated by scanning electron microscopy (SEM). [Arg]3M-
PONTX-Dq3a[1-15] and [Arg]4M-PONTX-Dq3a[1-15], both arginine-substituted, showed the
lowest MIC and MLC values (both 0.78 μM). In the biofilm formation assays, the peptide
[Arg]3M-PONTX-Dq3a [1-15] showed a MBIC of 3.12 μM for the two strains tested. Both
peptides were able to change the permeability of the membrane around 80%. The treatment at
MIC was able to eliminate bacteria after 2 hours of contact. For treatment with half of the MIC,
both strains had a constancy in the number of bacteria up to 12h, which may indicate a
bacteriostatic effect. SEM showed that the treatment at the lowest concentration (0.78 μM) of
both peptides provided disruption of the cell membrane, destabilized the intercellular
interaction and the CLM of [Arg]4M-PONTX-Dq3a [1-15] caused the complete eradication of
the bacteria. Thus, this study describes two AMP active against MSSA and MRSA and also are
able to inhibit the formation of their biofilms. [Arg]3M-PONTX-Dq3a[1-15] and [Arg]4M-
PONTX-Dq3a[1-15] emerge as a new alternative for research substances for the treatment of
resistant and/or biofilm-forming strains.
Tipo: Dissertação2024-01-01T00:00:00Z