Quality attributes of CTVad1, a nanoemulsified adjuvant for phase I clinical trial of SpiN COVID-19 vaccine.

Aim: To develop, characterize and evaluate an oil/water nanoemulsion with squalene (CTVad1) to be approved as an adjuvant for the SpiN COVID-19 vaccine clinical trials. Materials & methods: Critical process parameters (CPPs) of CTVad1 were standardized to meet the critical quality attributes (CQAs) of an adjuvant for human use. CTVad1 and the SpiN-CTVad1 vaccine were submitted to physicochemical, stability, in vitro and in vivo studies. Results & conclusion: All CQAs were met in the CTVad1 production process. SpiN- CTVad1 met CQAs and induced high levels of antibodies and specific cellular responses in in vivo studies. These results represented a critical step in the process developed to meet regulatory requirements for the SpiN COVID-19 vaccine clinical trial.

Cisplatin-Loaded Thermosensitive Liposomes Functionalized with Hyaluronic Acid: Cytotoxicity and In Vivo Acute Toxicity Evaluation.

Cisplatin (CDDP) is a potent antitumor drug used in first-line chemotherapy against several solid tumors, including breast cancer. However, toxicities and drug resistance limit its clinical application. Thermosensitive liposome (TSL) functionalized with hyaluronic acid (HA) containing cisplatin (TSL-CDDP-HA) was developed by our research group aiming to promote the release of CDDP in the tumor region under hyperthermia conditions, as well as to decrease toxicity. Thus, this study aimed to evaluate this new formulation (HA-coated TSL-CDDP) concerning in vitro behavior and in vivo toxicity compared to non-coated TSL-CDDP and free CDDP. Cytotoxicity assays and nuclear morphology were carried out against triple-negative breast cancer cells (MDA-MB-231), while an in vivo toxicity study was performed using healthy Swiss mice. The results showed an increase (around 3-fold) in cytotoxicity of the cationic formulation (non-coated TSL-CDDP) compared to free CDDP. On the other hand, TSL-CDDP treatment induced the appearance of 2.5-fold more senescent cells with alteration of nuclear morphology than the free drug after hyperthermia condition. Furthermore, the association of liposomal formulations treatment with hyperthermia increased the percentage of apoptotic cells compared to those without heating. The percentage of apoptotic cells was 1.7-fold higher for TSL-CDDP-HA than for TSL-CDDP. For the in vivo toxicity data, the TSL-CDDP treatment was also toxic to healthy cells, inducing nephrotoxicity with a significant increase in urea levels compared to the saline control group (73.1 ± 2.4 vs. 49.2 ± 2.8 mg/mL). On the other hand, the HA-coated TSL-CDDP eliminated the damages related to the use of CDDP since the animals did not show changes in hematological and biochemical examinations and histological analyses. Thus, data suggest that this new formulation is a potential candidate for the intravenous therapy of solid tumors.

Perfil dos pacientes chagásicos portadores de cardioversor-desfibrilador implantável (CDI) / Profile of chagasic patients with implantable cardioverter cefibrillators (ICD)

Fundamentos: A morte súbita é responsável por 55-65% dos óbitos na doença de Chagas, e o cardioversor desfibrilador implantável (CDI) é a terapêutica mais efetiva para evitar morte súbita em pacientes com taquiarritmias ventriculares. Objetivo: Descrever o perfil clínico dos pacientes portadores de cardiopatia chagásica crônica com CDI internados em hospital de referência.Métodos: Foram avaliados 75 pacientes chagásicos, portadores de CDI, internados na Santa Casa de Misericórdia de Goiânia no período de janeiro de 2011 a dezembro de 2013, mediante revisão de prontuários. Resultados: A amostra (n=75) se constituiu de 57 (76,0%) pacientes do sexo masculino e 18 (24,0%) do sexo feminino. As internações clínicas representaram 60,0% da amostra e as de causas cirúrgicas 40,0%. Das causas clínicas, 40 (89,0%) foram de origem cardíaca: insuficiência cardíaca (IC) com 13 (32,0%) pacientes e a tempestade elétrica (TE) com 12 (30,0%) pacientes. Das 30 causas cirúrgicas, 17 (56,66%) se deveram a desgaste da bateria.Conclusão: O perfil clínico encontrado em pacientes portadores de cardiopatia chagásica crônica com CDI apresenta as seguintes características: sexo masculino, faixa etária entre 51-60 anos, presença de dispositivos de dupla-câmara, uso adequado de antiarrítmico e beta bloqueador, presença de hipertensão arterial sistêmica (HAS), fração de ejeção do ventrículo esquerdo (FEVE) entre 35-45%, internações clínicas por causas cardíacas (em especial IC e TE), e número de internações pós-implante entre zero e três.

Background: Sudden death accounts for 55-65% of the deaths from Chagas disease, and the implantable cardioverter-defibrillator (ICD) is the most effective therapy to prevent sudden death in patients with ventricular tachyarrhythmias. Objective: To describe the clinical profile of patients with chronic Chagas disease with ICD admitted to a referral hospital. Methods: 75 chagasic patients with ICD, admitted to Santa Casa de Misericórdia de Goiânia, from January 2011 to December 2013, were evaluated by means of medical record review.Results: The sample (n=75) was composed of 57 (76.0%) male patients and 18 (24.0%) female patients. Clinical admissions accounted for 60.0% of the sample, while surgical ones accounted for 40.0%. Out of all clinical admissions, 40 (89.0%) were due to heart problems: heart failure (HF), with 13 (32.0%) patients, and electrical storm (ES), with 12 (30.0%) patients. Out of the 30 surgical admissions, 17 (56.66%) were due to battery depletion.Conclusion: The clinical profile of patients with chronic Chagas disease with CDI is characterized as follows: male, aged 51-60, presence of dual-chamber devices, appropriate use of antiarrhythmic drugs and beta-blockers, presence of systemic hypertension (SH),left ventricular ejection fraction (LVEF) of 35-45%, clinical admissions due to heart problems (particularly HF and ES), and zero to three post-implantation admissions.