RESUMO
OBJECTIVE: The aim of the study was to evaluate the safety profile of nirmatrelvir-ritonavir (NMV-r) in real clinical practice and to analyze the clinical relevance of drug-drug interactions in the development of adverse events. METHODS: Observational, retrospective study in which safety data of patients treated with NMV-r between April and July 2022 in an outpatient setting were evaluated. The duration of follow-up was 28 days and the number of adverse reactions reported, as well as whether they were managed on an outpatient basis or required health care, and the presence of renal and hepatic function impairment were assessed. Concomitant treatment was reviewed, identifying theoretical drug-drug interactions (TDDIs) whose severity was defined using the Lexi-interact classification. RESULTS: The study included 146 patients, 82 (56,16%) were women, whose median age was 65 years (22-95). The number of TDDIs detected and maintained during treatment with NMV-r was 164, with the percentage of patients with at least one interaction being 62,33%. The median number of TDDIs per patient was 1 (0-5). At least 1 adverse event (AE) was reported in 18 patients (11,84%). Eleven AEs were potentially related to any TDDI. Seven patients required contact with hospital assistance for AE management. Eight patients had impaired renal function and 2 had impaired liver function at 28 days. The main groups of drugs implicated in the occurrence of an AE were oral anticoagulants and calcium antagonists. CONCLUSIONS: Our results show a high number of TDDIs detected were detected between NMV-r and other drugs. This study provides greater knowledge of the drugs involved in such interactions and their potential relationship with the occurrence of adverse events.
Assuntos
Lactamas , Leucina , Nitrilas , Pacientes Ambulatoriais , Prolina , Ritonavir , Idoso , Feminino , Humanos , Masculino , Antivirais/efeitos adversos , Interações Medicamentosas , Estudos Retrospectivos , Ritonavir/efeitos adversos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: The aim of the study was to evaluate the safety profile of nirmatrelvir-ritonavir (NMV-r) in real clinical practice and to analyse the clinical relevance of drug-drug interactions in the development of adverse events. METHODS: Observational, retrospective study in which safety data of patients treated with NMV-r between April and July 2022 in an outpatient setting were evaluated. The duration of follow-up was 28â¯days and the number of adverse reactions reported, as well as whether they were managed on an outpatient basis or required health care, and the presence of renal and hepatic function impairment were assessed. Concomitant treatment was reviewed, identifying theoretical drug-drug interactions (TDDIs) whose severity was defined using the Lexi-interact classification. RESULTS: The study included 146 patients. 82 (56.16%) were women, whose median age was 65â¯years (22-95). the number of TDDIs detected and maintained during treatment with NMV-r was 164, with the percentage of patients with at least 1 interaction being 62.33%. The median number of TDDIs per patient was 1 (0-5). At least 1 adverse event (AE) was reported in 18 patients (11.84%). 11 AEs were potentially related to any TDDI. 7 patients required contact with hospital assistance for AE management. 8 patients had impaired renal function and 2 had impaired liver function at 28â¯days. The main groups of drugs implicated in the occurrence of an AE were oral anticoagulants and calcium antagonists. CONCLUSIONS: Our results show a high number of TDDIs detected were detected between NMV-r and other drugs. This study provides greater knowledge of the drugs involved in such interactions and their potential relationship with the occurrence of adverse events.
Assuntos
Lactamas , Leucina , Nitrilas , Pacientes Ambulatoriais , Prolina , Ritonavir , Humanos , Feminino , Idoso , Masculino , Ritonavir/efeitos adversos , Estudos Retrospectivos , Anticoagulantes , AntiviraisRESUMO
Chitosan nanoparticles (CSNPs) ionically crosslinked with tripolyphosphate salts (TPP) were employed as nanocarriers in combined drug delivery and magnetic hyperthermia (MH) therapy. To that aim, three different ferrofluid concentrations and a constant 5-fluorouracil (5-FU) concentration were efficiently encapsulated to yield magnetic CSNPs with core-shell morphology. In vitro experiments using normal cells, fibroblasts (FHB) and cancer cells, human glioblastoma A-172, showed that CSNPs presented a dose-dependent cytotoxicity and that they were successfully uptaken into both cell lines. The application of a MH treatment in A-172 cells resulted in a cell viability of 67-75% whereas no significant reduction of cell viability was observed for FHB. However, the A-172 cells showed re-growth populations 4h after the application of the MH treatment when CSNPs were loaded only with ferrofluid. Finally, a combined effect of MH and 5-FU release was observed with the application of a second MH treatment for CSNPs exhibiting a lower amount of released 5-FU. This result demonstrates the potential of CSNPs for the improvement of MH therapies.
Assuntos
Quitosana/química , Sistemas de Liberação de Medicamentos , Magnetismo , Nanopartículas/química , Linhagem Celular Tumoral , Fluoruracila , Humanos , Técnicas In VitroRESUMO
A series of thermoresponsive copolymers based on chitosan-g-poly(N-vinylcaprolactam) were synthesized by amidation reaction using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride as coupling reagent. The effect of molecular architecture on the thermoresponsive properties of the graft copolymers solutions was studied by varying the chain length of the grafted poly(N-vinylcaprolactam), PVCL, (in the range from 4 to 26 kDa) and the spacing between grafted chains onto the chitosan backbone. The most interesting characteristic of these copolymers is their solubility in water at temperatures below their lower critical solution temperature (LCST). These solutions presented a LCST between 36 and 44 °C, which decreases with the spacing and length of grafted PVCL chains onto the chitosan backbone, in contrast with the limited decrease of the LCST of PVCL above a critical M¯n value around 18 kDa. This behavior offers tangible possibilities for the preparation and application of sensitive bioactive formulations and "smart" drug delivery systems.
Assuntos
Caprolactama/análogos & derivados , Quitosana/análogos & derivados , Preparações de Ação Retardada/química , Polímeros/química , Caprolactama/síntese química , Caprolactama/química , Quitosana/síntese química , Preparações de Ação Retardada/síntese química , Concentração de Íons de Hidrogênio , Morfolinas/síntese química , Morfolinas/química , Polímeros/síntese química , Solubilidade , Temperatura , Água/químicaRESUMO
Natural products using plants have received considerable attention because of their potential to treat various diseases. Arrabidaea chica (Humb. & Bonpl.) B. Verlot is a native tropical American vine with healing properties employed in folk medicine for wound healing, inflammation, and gastrointestinal colic. Applying nanotechnology to plant extracts has revealed an advantageous strategy for herbal drugs considering the numerous features that nanostructured systems offer, including solubility, bioavailability, and pharmacological activity enhancement. The present study reports the preparation and characterization of chitosan-sodium tripolyphosphate nanoparticles (NPs) charged with A. chica standardized extract (AcE). Particle size and zeta potential were measured using a Zetasizer Nano ZS. The NP morphological characteristics were observed using scanning electron microscopy. Our studies indicated that the chitosan/sodium tripolyphosphate mass ratio of 5 and volume ratio of 10 were found to be the best condition to achieve the lowest NP sizes, with an average hydrodynamic diameter of 150±13 nm and a zeta potential of +45±2 mV. Particle size decreased with AcE addition (60±10.2 nm), suggesting an interaction between the extract's composition and polymers. The NP biocompatibility was evaluated using human skin fibroblasts. AcE-NP demonstrated capability of maintaining cell viability at the lowest concentrations tested, stimulating cell proliferation at higher concentrations. Antiulcerogenic activity of AcE-NP was also evaluated with an acute gastric ulcer experimental model induced by ethanol and indomethacin. NPs loaded with A. chica extract reduced the ulcerative lesion index using lower doses compared with the free extract, suggesting that extract encapsulation in chitosan NPs allowed for a dose reduction for a gastroprotective effect. The AcE encapsulation offers an approach for further application of the A. chica extract that could be considered a potential candidate for ulcer-healing pharmaceutical systems.
Assuntos
Bignoniaceae/química , Quitosana/química , Portadores de Fármacos/química , Nanopartículas/química , Extratos Vegetais/farmacologia , Polifosfatos/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Etanol/efeitos adversos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Indometacina/efeitos adversos , Masculino , Tamanho da Partícula , Compostos Fitoquímicos , Ratos , Ratos Wistar , Pele/citologia , Pele/efeitos dos fármacos , Pele/metabolismo , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológicoRESUMO
The article deals with the design, preparation, and evaluation of a new bilayered dressing for application in the healing of compromised wounds. The system is based on the sequential release of two complementary bioactive components to enhance the activation of the regeneration of dermal tissue. The internal layer is a highly hydrophilic and biodegradable film of gelatin and hyaluronic acid (HG), crosslinked with the natural compound genipin, which reacts with the amine groups of gelatin. This film is loaded with the proangiogenic, anti-inflammatory, and antibacterial peptide, proadrenomedullin N-terminal 20 peptide (PAMP), that is released slowly in the wound site. The external layer, more stable and less hydrophilic, is constituted by a biodegradable polyurethane derived from poly(caprolactone) and pluronic L61. This layer is loaded with resorbable nanoparticles of bemiparin (a fractionated low molecular weight heparin), which promotes the activation of growth factors, FGF and VEGF, and provides a good biomechanical stability and controlled permeability of the bilayered dressing. Experiments carried out in mice demonstrate the excellent angiogenic effect of the HG film in the dermal tissue. Application of the bilayered dressing in the wound healing rabbit ear model shows an improved cicatrization of the wound in both ischemic and non-ischemic defects, favoring epithelialization and reducing noticeably the contraction and the inflammation.
Assuntos
Adrenomedulina/administração & dosagem , Bandagens , Heparina de Baixo Peso Molecular/administração & dosagem , Regeneração/efeitos dos fármacos , Pele/crescimento & desenvolvimento , Pele/lesões , Implantes Absorvíveis , Animais , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Combinação de Medicamentos , Heparina de Baixo Peso Molecular/química , Masculino , Camundongos , Coelhos , Regeneração/fisiologia , Pele/efeitos dos fármacos , Adesivo Transdérmico , Resultado do Tratamento , Cicatrização/efeitos dos fármacosRESUMO
Novel gradient copolymers of hydrophilic 1-vinylimidazol and hydrophobic methacrylic derivative of ibuprofen prepared by free radical polymerization are described. The heterogeneous distribution of monomeric units along the polymeric chains leads to a gradient distribution of the hydrophobic and hydrophilic sequences responsible of nanoparticles formation through a self-assembling mechanism, capable of tune the water permeation due to the ionizable imidazole moieties and their gradient profile along the macromolecules, exhibiting pH and composition dependent effect in terms of diameter, zeta potential, acid-base buffering, ibuprofen release and chelating capacities, responsible of matrix metalloproteinase dysfunction showing anti-inflammatory activity in a nitric oxide inhibition assay.
Assuntos
Anti-Inflamatórios/farmacologia , Quelantes/farmacologia , Ibuprofeno/farmacologia , Imidazóis/química , Metacrilatos/química , Polímeros/química , Zinco/química , Animais , Linhagem Celular , Vidro/química , Hidrodinâmica , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Peso Molecular , Nanopartículas/ultraestrutura , Óxido Nítrico/biossíntese , Polímeros/síntese química , Eletricidade Estática , Temperatura de TransiçãoRESUMO
2-Allyl-1-vinyl-ß-carbolines and dihydropyrrolo-ß-carbolines react with activated internal alkynes through novel rearrangement reactions leading to complex polycyclic structures. Favored reaction pathways depend on reaction conditions and on the presence of gold catalysts. In particular, upon reaction with 2 equiv. of the alkyne, new hexacyclic structures 10 are formed with total stereocontrol.