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- Nose-to-brain delivery of lipid-based nanosystems for epileptic seizures and anxiety crisisPublication . Costa, C.; Moreira, J.N.; Amaral, M.H.; Lobo, J.M. Sousa; Silva, Ana CatarinaEpileptic seizures and anxiety crisis are severe conditions that require fast and effective treatment, targeting the brain. Current emergency antiepiletics and anxiolytics have limited brain bioavailability, following oral, intravenous or rectal administration. This relates with the limited extent at which these drugs bypass the blood brain barrier (BBB). Thereby, the development of strategies that significantly improve the brain bioavailability of these drugs, along with a simple and safe administration by patients, attenuating and/or preventing epileptic seizures or anxiety crisis, are still a major need. In this respect, the nasal/intranasal route has been suggested as a promising strategy for drug targeting to the brain, thus avoiding the BBB. Besides, the use of lipid-based nanosystems, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), liposomes, nanoemulsions and microemulsions, have been demonstrating high efficiency for nose-to-brain transport. This review highlights the potential of using lipid-based nanosystems in the management of epilepsy and anxiety, by means of the nasal/intranasal route. So far, the reported studies have shown promising results, being required more in vivo experiments to further advance for clinical trials. Furthermore, toxicological concerns related to the need of evaluate the impairment on the mucociliary clearance mechanism have been pointed.
- Medicamentos biossimilares – aplicação no tratamento do cancroPublication . Silva, Ana Catarina; Santos, S.Os medicamentos biossimilares surgiram após expirarem as primeiras patentes dos medicamentos biológicos, tendo sido legislados pela União Europeia em 2005, e sendo definidos como aqueles que, quando produzidos por um novo fabricante, demonstram similaridade com um medicamento biológico previamente aprovado, designado medicamento biológico de referência. Neste sentido, um medicamento biossimilar tem de demonstrar a mesma qualidade, segurança e eficácia que o medicamento biológico original. Os medicamentos biossimilares constituem uma alternativa económica, comparativamente aos medicamentos biológicos, já que dispensam a realização de alguns estudos dispendiosos, quando se demonstra que a sua atividade é semelhante à do medicamento biológico de referência. No entanto, comparativamente aos medicamentos genéricos clássicos, o desenvolvimento e fabrico dos medicamentos biossimilares é mais complexo e caro, uma vez que a sua eficácia e segurança têm de ser confirmadas com dados clínicos e/ou pré-clínicos.Na primeira parte deste trabalho são descritas as etapas cruciais do desenvolvimento dos medicamentos biossimilares, que vão desde a sua produção até à introdução no mercado. De seguida, são apresentados exemplos de medicamentos biossimilares usados na terapia do cancro na União Europeia. Nesta área, a sua aplicação é notável, de uma forma direta (no tratamento da doença propriamente dita) ou indireta (no tratamento dos efeitos secundários resultantes do tratamento da doença), tendo aumentado a acessibilidade da população à terapia com medicamentos biológicos, por se tratar de uma alternativa mais económica para os sistemas de saúde e, consequentemente, para o doente.
- Current progresses on nanodelivery systems for the treatment of neuropsychiatric diseases: Alzheimer’s and SchizophreniaPublication . Silva, Ana Catarina; González-Mira, E.; Lobo, J.M. Sousa; Amaral, M.H.Currently Alzheimer's disease and schizophrenia are both well-established neuropsychiatric diseases. Nonetheless, the treatment of these disorders is not unanimous and fully effective. As a consequence, several approaches have been studied to improve patient's conditions. In this context, the development of new drug nanodelivery systems to increase drug bioavailability and reduce adverse effects has been claimed as a good option. Among these systems we focus on the ones that seem to be most promising, such as lipidbased systems (e.g. liposomes, nanoemulsions and lipid nanoparticles), drug nanocrystals, polymeric nanoparticles and micelles. Moreover, the application of these systems by means of alternative administration routes is also discussed. Regardless of the satisfactory results and the associated progresses that have been done in the last years, more studies are required to quickly licence the application of drug nanodelivery systems in human medicines.
- Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: a current overview of in vivo studiesPublication . Costa, Cláudia Pina; Moreira, João Nuno; Lobo, José Manuel Sousa; Silva, Ana CatarinaThe management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers (SLNs, NLCs and NEs) for nose-to-brain delivery. Based on the literature available from the past two years, we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration. The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out. Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear, it appears that the intranasal route together with the use of NLCs, SLNs or NEs is advantageous for targeting drugs to the brain. These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs, so they are expected to be approved by regulatory authorities in the coming years.
- Células estaminais na regeneração da pele: aplicações terapêuticas e cosméticasPublication . Silva, Ana Catarina; Barata, RitaTendo em conta a capacidade das células estaminais para se autorrenovarem e diferenciarem em vários tipos de células do organismo, a sua utilização terapêutica torna-se interessante, por exemplo, ao nível da regeneração da pele. Nesse sentido, as células estaminais têm sido testadas para o tratamento/cicatrização de feridas originadas pela exposição ao calor e à radiação, bem como em úlceras diabéticas. A eficácia da utilização destas células tem sido demonstrada por vários investigadores, tendo-se verificado que promovem a reepitelização e a neovascularização, e reduzem a formação de cicatrizes, sem provocar respostas inflamatórias ou imunológicas. Também na área da cosmética tem sido observado o potencial das células estaminais, em particular, as células de origem vegetal, para retardar o processo natural de envelhecimento da pele, através da proteção das células estaminais autólogas e estimulação da sua proliferação. No entanto, é necessário realizar mais estudos clínicos e procurar novos ingredientes ativos, de forma a poder concluir, com maior rigor, a eficácia destas aplicações.
- Thermosensitive nasal in situ gels of lipid-based nanosystems to improve the treatment of Alzheimer’s DiseasePublication . Cunha, Sara; Forbes, Ben; Lobo, José Manuel Sousa; Silva, Ana CatarinaThermosensitive in situ gels are promising formulations for the management of Alzheimer’s disease (AD), since they increase the residence time of lipid-based nanosystems in the nasal cavity, improving drug therapeutic efficacy. The purpose of this study is to prepare thermosensitive in situ gels with anticholinesterase inhibitor (RVG)-loaded nanostructured lipid carriers (NLC) and nanoemulsions to improve the residence time of the formulations in the nasal cavity. Different concentrations of thermosensitive polymers were added to the RVG-loaded NLC and to the RVG-loaded nanoemulsion to optimize the gelation temperature of the in situ gels; concentrations of 17% (%, w/w) of Kolliphor® P407 and 0.3% (%, w/w) of MethocelTM K4M were selected. The in situ gels of the RVG-loaded NLC and RVG-loaded nanoemulsion had a particle size, PDI, ZP, and pH of, respectively: 141.70 ± 0.40 nm and 146.10 ± 1.73 nm; 0.45 ± 0.00 and 0.43 ± 0.02; −4.06 ± 1.03 mV and −4.09 ± 0.71 mV, 6.60 ± 0.01 and 7.00 ± 0.02. In addition, these in situ gels showed a non-Newtonian plastic behavior, and the texture parameters presented desirable values for nasal administration. From these results, we concluded that the developed in situ gels can be used to improve the treatment of AD through the nose-to-brain route.
- Risperidone release from solid lipid nanoparticles (SLN): validated HPLC method and modelling kinetic profilePublication . Silva, Ana Catarina; Lopes, Carla Martins; Fonseca, J.; Soares, M.E.; Santos, D.; Souto, Eliana B.; Ferreira, D.A simple reverse-phase (RP) high performance liquid chromatography (HPLC) method was developed and validated, according to the International Harmonisation Guidelines (ICH), for the determination of risperidone (RISP) from solid lipid nanoparticles (SLN). Chromatographic runs were performed on a RP-C18 column, using an isocratic mobile phase of methanol, acetate buffer (0.05 M; pH 4.6) and triethylamine (60:40:0.02, v/v/v). The flow rate was 1 ml/min, the run time was 10 min and the RISP absorbance was measured at 280 nm, using UV detection. A linear response was obtained for a RISP concentration range of 0.25 - 10.00 g/ml (R2 = 0.9996), with a detection and quantification limits of 0.011 and 0.034 g/ml, respectively. The method was shown to be specific, precise at the intra-day (RSD < 0.796%) and inter-day (RSD < 0.331%) levels, and accurate with recoveries between 86.86 - 100.3% (RSD < 0.613%). Method robustness was observed as well. The suitability of the method for RISP quantifications was assessed by the determination of encapsulation parameters (encapsulation efficiency and drug loading) and by studying the RISP release profile from SLN. Kinetic models (zero order, Higuchi, Korsmeyer-Peppas and Baker-Lonsdale) were used to fit the obtained release profile and to predict the in vivo performance of RISP-loaded SLN. A combined pattern of diffusion and erosion release mechanism (anomalous non-Fickian transport) was found for the RISP-loaded SLN, which shows the ability of the system for controlled drug release.
- Manual de apoio às aulas teóricas de Farmácia ComunitáriaPublication . Silva, Ana Catarina
- Manual de apoio às aulas teóricas de biotecnologia industrial farmacêuticaPublication . Silva, Ana Catarina
- Pessaries containing Nanostructured Lipid Carriers (NLC) for prolonged vaginal delivery of progesteronePublication . Correia, A.; Costa, C.P.; Silva, V.; Silva, R.; Lobo, J.M. Sousa; Silva, Ana CatarinaProgesterone (PRG) plays a crucial role in the female reproductive system, being the vaginal route the most adequate for its administration, as this drug has an extensive hepatic first pass effect. Nonetheless, vaginal PRG dosage forms originate immediate drug release and requires repeated administrations, which is unpleasant. Thereby, it is necessary to develop alternative delivery systems for prolonged vaginal release of PRG. The objective of this work was the development of pessaries for the prolonged vaginal delivery of PRG. Studies began with the preparation of an aqueous dispersion of PRG-loaded NLC (NLC_PRG), followed by the evaluation of its biocompatibility in human immortalized keratinocytes (HaCat cells), using three different methods (neutral red uptake, resazurin reduction and sulforhodamine B assays). Finally, the NLC_PRG was incorporated into pessaries, which were further characterized according to the European Pharmacopoeia to assess their suitability to prolong PRG release through the vaginal route. The results showed that, after preparation, 90% of the NLC_PRG had sizes equal or lower than 315.60 ± 0.01 nm, and an EE of 96.42 ± 0.00%. All the assays used to assess the biocompatibility of NLC_PRG showed the absence of cytotoxicity towards HaCaT cells for concentrations up to 10 μg/mL. In all cytotoxicity assays, a cytotoxic effect was only observed for concentrations equal or higher than 25 μg/mL, which provides high confidence in the obtained results. The outcomes of this study suggest the suitability of using pessaries containing PRG-loaded NLC for sustained drug release, which is an innovative therapeutic strategy and constitutes a promising alternative for the vaginal use of PRG. However, further ex vivo and in vivo studies are needed to fully clarify the pharmacokinetic and toxicological profile before reaching the clinical use.