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- 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.
- 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.
- Manual de apoio às aulas teóricas de Farmácia ComunitáriaPublication . Silva, Ana Catarina
- Double optimization of rivastigmine-loaded Nanostructured Lipid Carriers (NLC) for nose-to-brain delivery using the Quality by Design (QbD) approach: formulation variables and instrumental parametersPublication . Cunha, Sara; Costa, Cláudia Pina; Loureiro, Joana A.; Alves, Jorge; Peixoto, Andreia F.; Forbes, Ben; Sousa Lobo, José Manuel; Silva, Ana CatarinaRivastigmine is a drug commonly used in the management of Alzheimer's disease that shows bioavailability problems. To overcome this, the use of nanosystems, such as nanostructured lipid carriers (NLC), administered through alternative routes seems promising. In this work, we performed a double optimization of a rivastigmine-loaded NLC formulation for direct drug delivery from the nose to the brain using the quality by design (QbD) approach, whereby the quality target product profile (QTPP) was the requisite for nose to brain delivery. The experiments started with the optimization of the formulation variables (or critical material attributes-CMAs) using a central composite design. The rivastigmine-loaded NLC formulations with the best critical quality attributes (CQAs) of particle size, polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) were selected for the second optimization, which was related to the production methods (ultrasound technique and high-pressure homogenization). The most suitable instrumental parameters for the production of NLC were analyzed through a Box-Behnken design, with the same CQAs being evaluated for the first optimization. For the second part of the optimization studies, were selected two rivastigmine-loaded NLC formulations: one produced by ultrasound technique and the other by the high-pressure homogenization (HPH) method. Afterwards, the pH and osmolarity of these formulations were adjusted to the physiological nasal mucosa values and in vitro drug release studies were performed. The results of the first part of the optimization showed that the most adequate ratios of lipids and surfactants were 7.49:1.94 and 4.5:0.5 (%, w/w), respectively. From the second part of the optimization, the results for the particle size, PDI, ZP, and EE of the rivastigmine-loaded NLC formulations produced by ultrasound technique and HPH method were, respectively, 114.0 ± 1.9 nm and 109.0 ± 0.9 nm; 0.221 ± 0.003 and 0.196 ± 0.007; -30.6 ± 0.3 mV and -30.5 ± 0.3 mV; 97.0 ± 0.5% and 97.2 ± 0.3%. Herein, the HPH was selected as the most suitable production method, although the ultrasound technique has also shown effectiveness. In addition, no significant changes in CQAs were observed after 90 days of storage of the formulations at different temperatures. In vitro studies showed that the release of rivastigmine followed a non-Fickian mechanism, with an initial fast drug release followed by a prolonged release over 48 h. This study has optimized a rivastigmine-loaded NLC formulation produced by the HPH method for nose-to-brain delivery of rivastigmine. The next step is for in vitro and in vivo experiments to demonstrate preclinical efficacy and safety. QbD was demonstrated to be a useful approach for the optimization of NLC formulations for which specific physicochemical requisites can be identified.
- Hematopoietic growth factorsPublication . Silva, Ana Catarina; Moreira, João Nuno; Lobo, José Manuel Sousa
- Current applications of pharmaceutical biotechnologyPublication . Silva, Ana Catarina; Moreira, João Nuno; Lobo, José Manuel Sousa; Almeida, HugoThis book offers an authoritative review of biopharmaceuticals and their clinical relevance. Biopharmaceuticals have been showing high therapeutic potential by means of biological and biosimilar medicines, particularly for the treatment of cancer, chronic diseases (e.g. diabetes, Crohn's disease, psoriasis and rheumatoid arthritis), neurodegenerative disorders (e.g. multiple sclerosis), and they have also been contributing to the progress of innovative therapies such as assisted reproductive medicine. Since the eighties, several biopharmaceuticals have been approved and, due to patents expiration, many biosimilars are also marketed. In this book, readers will find the most relevant updated information about the main clinical applications of pharmaceutical biotechnology. The authors provide expert analysis about the industrial challenges of recombinant proteins and the different classes of biopharmaceuticals, including monoclonal antibodies, vaccines, growth factors and stem cells. Topics such as bioprinting technologies in tissue engineering, gene therapy and personalized medicine are also covered in this book. Professionals, students and researchers interested in this field will find this work an important account.
- Manual de apoio às aulas teóricas de novos sistemas terapêuticosPublication . Silva, Ana Catarina
- Manual de apoio às aulas teóricas de farmácia galénicaPublication . Silva, Ana Catarina
- Preparações vaginais: ontem, hoje e amanhãPublication . Silva, Ana Catarina; Lobo, José Manuel Sousa; Correia, Armanda do CarmoAs preparações farmacêuticas para aplicação vaginal são usadas desde a Antiguidade para tratar afeções vaginais. A atuação local de fármacos administrados na vagina promove a eficácia dos tratamentos e diminui possíveis efeitos tóxicos. Além disso, algumas moléculas pequenas e lipófilas conseguem permear a parede vaginal, sendo absorvidas para a corrente circulatória. A possibilidade de absorção sistémica através da vagina destaca-a como uma alternativa à via oral, com vantagens como o facto de evitar a primeira passagem hepática e os efeitos adversos gastrintestinais que se verificam com alguns fármacos. As formas farmacêuticas de libertação modificada permitem melhorar alguns aspetos da farmacocinética dos fármacos e tornam as administrações menos frequentes, o que promove a adesão à terapêutica e, consequentemente, a eficácia. As estratégias de libertação modificada para a via vaginal incluem sistemas de libertação, como anéis ou películas vaginais, sistemas mucoadesivos e nanossistemas. Novas possibilidades terapêuticas adequadas a esta via têm surgido, das quais se destacam a administração de microbicidas para prevenção da transmissão do virus da imunodeficiência humana e a administração de biofármacos, incluindo vacinas e anticorpos monoclonais com propriedades espermicidas, antivíricas e antifúngicas.
- Manual de apoio às aulas teóricas de biotecnologia industrial farmacêuticaPublication . Silva, Ana Catarina