Multifunctional nanocarriers for lung drug delivery

Nanocarriers have been increasingly proposed for lung drug delivery applications. The strategy of combining the intrinsic and more general advantages of the nanostructures with specificities that improve the therapeutic outcomes of particular clinical situations is frequent. These include the surface engineering of the carriers by means of altering the material structure (i.e., chemical modifications), the addition of specific ligands so that predefined targets are reached, or even the tuning of the carrier properties to respond to specific stimuli. The devised strategies are mainly directed at three distinct areas of lung drug delivery, encompassing the delivery of proteins and protein-based materials, either for local or systemic application, the delivery of antibiotics, and the delivery of anticancer drugs-the latter two comprising local delivery approaches. This review addresses the applications of nanocarriers aimed at lung drug delivery of active biological and pharmaceutical ingredients, focusing with particular interest on nanocarriers that exhibit multifunctional properties. A final section addresses the expectations regarding the future use of nanocarriers in the area.UID/Multi/04326/2019; PD/BD/137064/2018info:eu-repo/semantics/publishedVersio

Chitosan/dextran sulfate nanoparticles: stability evaluation and assessment of the effect of different acidic media on nanoparticle preparation

Dissertação de mestrado, Ciências Farmacêuticas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2016Nanoparticles present great potential in drug delivery applications, yet there are some issues regarding their stability. In this context, this study was conducted to define the conditions to stabilize polysaccharide (chitosan/dextran sulfate, CS/DS) nanoparticles by a process of freeze-drying, assessing the cryoprotectant capacity of two sugars (sucrose and glucose). Additionally, it was also intended to find if the solubilisation of chitosan in different acids affected nanoparticle preparation and characteristics. CS/DS nanoparticles were produced by polyelectrolyte complexation and the suspensions adjusted to 1 mg/mL or 2 mg/mL. For the study of stabilisation by freeze-drying, three approaches were conducted: i) after production of nanoparticles, 5% or 10% (w/v) of glucose or sucrose were included in the suspension before freezing, being nanocarriers characterized for size and zeta potential before freeze-drying and immediately after freeze-drying and reconstitution; ii) nanoparticles were produced, and then stored at 4 ºC (no cryoprotectants added); iii) nanoparticles were produced, freeze-dried with cryoprotectants and then stored, in a desiccator, at room temperature, being characterized (size and zeta potential) every 15 days, after the needed reconstitution. Acetic acid and hydrochloric acid (HCl) at 0.1 and 0.01 M were used to solubilise chitosan. CS dissolved in HCl 0.1 M did not enable the production of nanoscale particles. When the remaining acids were test, nanoparticles had sizes above 500 nm. Furthermore, zeta potential presented an unexpected behaviour. Thus, it was concluded that this study needs optimisation. The storage of nanoparticle suspensions at 4 ºC resulted in instability after 50 days. Therefore, a freeze-drying approach was established. In general, the choice of cryoprotectant was the most important factor affecting the preservation of nanoparticle physicochemical characteristics. Moreover, results indicated that in short- and long-term periods, glucose presented a more suitable behaviour despite some variations.As nanopartículas apresentam-se como uma interessante estratégia de veiculação de fármacos. Contudo, a sua estabilidade é uma limitação desenhado este estudo que pretende estabelecer condições de estabilização de nanopartículas polissacarídicas (quitosano/sulfato de dextrano, CS/DS) através de um processo de liofilização, avaliando-se a capacidade crioprotetora de dois açúcares. Adicionalmente, procurou-se entender a influência de diferentes ácidos usados na dissolução do quitosano no tamanho e potencial zeta das nanopartículas produzidas. Nanopartículas de CS/DS foram preparadas por complexação polieletrolítica e as suspensões ajustadas a concentrações de 1 e 2 mg/mL. Para a abordagem da liofilização, foram delineados 3 ensaios: i) após a produção das nanopartículas, foi adicionado crioprotetor à suspensão antes do congelamento e a sua caracterização foi realizada imediatamente após a liofilização; ii) as nanopartículas foram produzidas e armazenadas a 4 ºC, sem qualquer adição de crioprotetor e iii) as nanopartículas foram produzidas, liofilizadas com crioprotetor, e armazenadas num exsicador, à temperatura ambiente, tendo sido caracterizadas de 15 em 15 dias. O ácido acético e o ácido clorídrico (HCl) a 0.1 M e 0.01 M foram os ácidos usados para solubilizar o quitosano. Os veículos derivados do uso de quitosano dissolvido em HCl 0.1 M encontraram-se fora da escala nanométrica. Por outro lado, nos restantes, os tamanhos ficaram acima dos 500 nm. Além disso, o potencial zeta demonstrou uma tendência inesperada, pelo que este estudo requer otimização. O armazenamento de nanosuspensões a 4 ºC resultou em parâmetros de caracterização instáveis, a partir do dia 50. Desta forma, estabeleceu-se um protocolo de liofilização em que, no geral, a escolha do crioprotector foi o fator determinante que afeta a preservação das características fisico-químicas das nanopartículas. Além disso, os resultados sugerem que a glucose possui uma melhor capacidade crioprotetora, a curto e longo prazos, apesar das grandes variações que os dados revelaram

Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles

Despite the existence of effective oral therapy, tuberculosis remains a deadly pathology, namely because of bacterial resistance and incompliance with treatments. Establishing alternative therapeutic approaches is urgently needed and inhalable therapy has a great potential in this regard. As pathogenic bacteria are hosted by alveolar macrophages, the co-localisation of antitubercular drugs and pathogens is thus potentiated by this strategy. This work proposes inhalable therapy of pulmonary tuberculosis mediated by a single locust bean gum (LBG) formulation of microparticles associating both isoniazid and rifabutin, complying with requisites of the World Health Organisation of combined therapy. Microparticles were produced by spray-drying, at LBG/INH/RFB mass ratio of 10/1/0.5. The aerodynamic characterisation of microparticles revealed emitted doses of more than 90% and fine particle fraction of 38%, thus indicating the adequacy of the system to reach the respiratory lung area, thus partially the alveolar region. Cytotoxicity results indicate moderate toxicity (cell viability around 60%), with a concentration-dependent effect. Additionally, rat alveolar macrophages evidenced preferential capture of LBG microparticles, possibly due to chemical composition comprising mannose and galactose units that are specifically recognised by macrophage surface receptors. (C) 2017 Elsevier B.V. All rights reserved.National Portuguese funding through FCT - Fundacao para a Ciencia e a Tecnologia [PTDC/DTP-FTO/0094/2012, UID/BIM/04773/2013, UID/Multi/04326/2013, UID/QUI/00100/2013, PEst-OE/QUI/UI4023/2011

Sulphated locust bean gum-coated lipid nanocapsules as potential lung delivery carriers

Drugs pertaining to Biopharmaceutics Classification System (BCS) classes II and IV have limitations in their delivery, including in the lung. Therefore, drug delivery carriers have been proposed to improve the therapeutic effectiveness of such drugs. This work proposes lipid nanocapsules (LNC) as a potential platform for lung drug delivery. Locust bean gum (LBG), which is a galactomannan, was used as polymeric shell, protecting the oily core of the nanocapsules and providing their surface with hydrophilic character. Due to the neutral character of LBG, in order to enable nanocapsule formation, a sulphate derivative (LBGS) was prepared, which was confirmed by Fourier-transformed infrared (FTIR) spectroscopy. The electrostatic interaction between the negatively charged sulphate groups of LBGS and the positively charged groups of the used cationic lipid (1,2-dioleoyloxy-3- trimethylammoniumpropanchloride, DOTAP), allowed the formation of monodisperse nanocapsules, with sizes around 200 nm and strongly negative zeta potentials, between -70 and -85 mV. Envisaging potential lung drug delivery, the LBGS-coated LNC were co-formulated with mannitol using spray-drying, producing microencapsulated nanocapsules. Feret’s diameter was determined to be 2.6 ± 1.8 µm and 3.1 ± 1.9 µm for Man (control) and Man/LNC microparticles, respectively. Further studies are underway in order to optimise both the nanoplatform and the dry powder formulation

Fucoidan from Fucus Vesiculosus: Evaluation of the impact of the Sulphate content on Nanoparticle production and Cell toxicity

The composition of seaweeds is complex, with vitamins, phenolic compounds, minerals, and polysaccharides being some of the factions comprising their structure. The main polysaccharide in brown seaweeds is fucoidan, and several biological activities have been associated with its structure. Chitosan is another marine biopolymer that is very popular in the biomedical field, owing to its suitable features for formulating drug delivery systems and, particularly, particulate systems. In this work, the ability of fucoidan to produce nanoparticles was evaluated, testing different amounts of a polymer and using chitosan as a counterion. Nanoparticles of 200–300 nm were obtained when fucoidan prevailed in the formulation, which also resulted in negatively charged nanoparticles. Adjusting the pH of the reaction media to 4 did not affect the physicochemical characteristics of the nanoparticles. The IC50 of fucoidan was determined, in both HCT−116 and A549 cells, to be around 160 µg/mL, whereas it raised to 675–100 µg/mL when nanoparticles (fucoidan/chitosan = 2/1, w/w) were tested. These marine materials (fucoidan and chitosan) provided features suitable to formulate polymeric nanoparticles to use in biomedical applications.info:eu-repo/semantics/publishedVersio

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Mammals in Portugal: a data set of terrestrial, volant, and marine mammal occurrences in Portugal

Mammals are threatened worldwide, with ~26% of all species being included in the IUCN threatened categories. This overall pattern is primarily associated with habitat loss or degradation, and human persecution for terrestrial mammals, and pollution, open net fishing, climate change, and prey depletion for marine mammals. Mammals play a key role in maintaining ecosystems functionality and resilience, and therefore information on their distribution is crucial to delineate and support conservation actions. MAMMALS IN PORTUGAL is a publicly available data set compiling unpublished georeferenced occurrence records of 92 terrestrial, volant, and marine mammals in mainland Portugal and archipelagos of the Azores and Madeira that includes 105,026 data entries between 1873 and 2021 (72% of the data occurring in 2000 and 2021). The methods used to collect the data were: live observations/captures (43%), sign surveys (35%), camera trapping (16%), bioacoustics surveys (4%) and radiotracking, and inquiries that represent less than 1% of the records. The data set includes 13 types of records: (1) burrows | soil mounds | tunnel, (2) capture, (3) colony, (4) dead animal | hair | skulls | jaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8), observation in shelters, (9) photo trapping | video, (10) predators diet | pellets | pine cones/nuts, (11) scat | track | ditch, (12) telemetry and (13) vocalization | echolocation. The spatial uncertainty of most records ranges between 0 and 100 m (76%). Rodentia (n =31,573) has the highest number of records followed by Chiroptera (n = 18,857), Carnivora (n = 18,594), Lagomorpha (n = 17,496), Cetartiodactyla (n = 11,568) and Eulipotyphla (n = 7008). The data set includes records of species classified by the IUCN as threatened (e.g., Oryctolagus cuniculus [n = 12,159], Monachus monachus [n = 1,512], and Lynx pardinus [n = 197]). We believe that this data set may stimulate the publication of other European countries data sets that would certainly contribute to ecology and conservation-related research, and therefore assisting on the development of more accurate and tailored conservation management strategies for each species. There are no copyright restrictions; please cite this data paper when the data are used in publications