Percorrer por autor "Fortuna, Ana"
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- Amorphous nasal powder advanced performance : in vitro/ex vivo studies and correlation with in vivo pharmacokineticsPublication . Henriques, Patrícia; Bicker, Joana; Carona, Andreia; Miranda, Margarida; Vitorino, Carla; Doktorovová , Slavomíra; Fortuna, AnaPurpose: Amorphous solid dispersions (ASD) for nasal delivery offer the opportunity to increase drug release performance, while using polymers with mucoadhesive properties. The aim of the present study was to apply this solubility enhancement technique to a poorly soluble drug for nasal delivery, while comparing two particle engineering strategies, namely spray dried microparticles and chimeral agglomerates, with the corresponding physical blends with crystalline drug. Methods: Formulations of piroxicam were manufactured using varied polymer and particle engineering strategies and evaluated through in vitro drug release and ex vivo permeation studies, as well as nasal deposition and in vivo pharmacokinetic studies. Results: ASD with hydroxypropyl methylcellulose (HPMC) showed enhanced drug release and permeation, compared to polyvinylpyrrolidone/vinyl acetate formulations and blends. Nasal deposition of HPMC chimeral agglomerates suggested off-target deposition. In vivo pharmacokinetic studies revealed that spray-dried HPMC-containing microparticles exhibited the highest maximum plasma concentration (Cmax) and the lowest time to attain it (tmax). In vitro release rate and in vivo absorption rate were correlated as well as tmax and in vitro performance. When excluding the formulation with least nasal targeted deposition, in vitro release and ex vivo permeation performance were also correlated with Cmax and area under the drug concentration-time curve (AUC) from 0 to 1 h, with R2 > 0.89. Conclusion: ASD for nasal delivery provide fast drug absorption, which depends on the supersaturation ability of the polymer employed. In vitro-in vivo correlations suggested that in vitro release and ex vivo permeation studies are predictive tools regarding nasal absorption.
- Impact of Sarcopenia on prognosis, treatment toxicity and surgical complications in locally advanced gastric cancerPublication . Dias, David da Silva; Luz, Paulo; Fortuna, Ana; Águas, Ana; Machado, Mafalda; Gosálbez, Beatriz; Farate, Rosa; Pinho, Rita Clemente; Valente, Ana Carmo; Mendes, José Leão; Seladas, Marta Maria; Trabulo, Carolina; Ravasco, PaulaBackground: Weight loss and skeletal muscle wasting are frequent in cancer and may influence treatment tolerance and outcomes. Computed tomography (CT) based body composition analysis at the third lumbar vertebra (L3) is an accurate method to quantify skeletal muscle in routine oncology care. Methods: We performed a multicenter retrospective cohort study including 202 adults with locally advanced (stage IB–III) gastric cancer treated in four Portuguese hospitals (January 2020–December 2022). Skeletal muscle area (SMA) was assessed on baseline CT at the L3 vertebral level, using Data Analysis Facilitation Suite (DAFS) software v3.11.2, and skeletal muscle index (SMI) was subsequently calculated. Patients with low muscle quantity were classified as sarcopenic (below sex-specific SMI mean). We evaluated associations with relapse-free survival (RFS), overall survival (OS), FLOT chemotherapy dose-limiting toxicities (DLTs), and postoperative complications after gastrectomy. Results: Mean age was 69 years, 65% had ECOG PS 0, 53% received FLOT chemotherapy protocol. Mean SMI was 49.6 cm2/m2 in males and 40.9 cm2/m2 in females and correlated positively, though moderately, with BMI (p < 0.01; r = 0.424). Sarcopenia was not significantly associated with RFS (p = 0.186) or OS (p = 0.168) at 30-month follow-up. Although numerical differences were observed (64% vs. 56% of patients did not relapse and 74% vs. 63% were alive, for non-sarcopenic vs. sarcopenic patients). Sarcopenia was associated with a higher risk of DLTs (p = 0.021; OR 2.56, 95% CI 1.15–5.73) and postoperative complications (p = 0.024; OR 2.16, 95% CI 1.11–4.21). Conclusions: Sarcopenia significantly increases the risk of chemotherapy toxicity and postoperative complications in locally advanced gastric cancer. However, its effect on OS and RFS was not statistically significant at 30-month follow-up. Standardization of CT-based sarcopenia cut-offs remains a major barrier to clinical implementation.