Browsing by Author "Forbes, Ben"
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- Engineering of konjac glucomannan into respirable microparticles for delivery of antitubercular drugsPublication . Guerreiro, Filipa; Swedrowska, Magda; Patel, Roshnee; Floréz- Fernández, Noelia; Torres, María Dolores; Rosa Da Costa, Ana M.; Forbes, Ben; Grenha, AnaFew medically-approved excipients are available for formulation strategies to endow microcarriers with improved performance in lung drug targeting. Konjac glucomannan (KGM) is a novel, biocompatible material, comprising mannose units potentially inducing macrophage uptake for the treatment of macrophage-mediated diseases. This work investigated spray-dried KGM microparticles as inhalable carriers of model antitubercular drugs, isoniazid (INH) and rifabutin (RFB). The polymer was characterised and different polymer/drug ratios tested in the production of microparticles for which respirability was assessed in vitro. The swelling of KGM microparticles and release of drugs in simulated lung fluid were characterised and the biodegradability in presence of beta-mannosidase, a lung hydrolase, determined. KGM microparticles were drug loaded with 66-91% association efficiency and had aerodynamic diameter around 3 mu m, which enables deep lung penetration. The microparticles swelled upon liquid contact by 40-50% but underwent size reduction (>62% in 90 min) in presence of beta-mannosidase, indicating biodegradability. Finally, drug release was tested showing slower release of RFB compared with INH but complete release of both within 24 h. This work identifies KGM as a biodegradable polymer of natural origin that can be engineered to encapsulate and release drugs in respirable microparticles with physical and chemical macrophage-targeting properties.
- In vitro behaviour of konjac glucomannan microparticles aimed at pulmonary tuberculosis therapyPublication . Guerreiro, Filipa; Swedrowska, Magda; Rosa Da Costa, Ana; Grenha, Ana; Forbes, BenTuberculosis is one of the highest causes of death worldwide. Long periods of treatment are required and result in some cases in therapeutic incompliance, potentiating the development of multidrug-resistant tuberculosis. Thus, new approaches to treat the infection are required as an alternative to conventional orally administered treatment. This work proposes the development of an inhalable system, which is specifically targeted to alveolar macrophages, where the Mycobacterium tuberculosis is located. The targeting is mainly driven by the selected matrix material, konjac glucomannan (KGM), a natural polymer comprising mannan units that are expected to potentiate phagocytosis. Microparticles were loaded with two antitubercular drugs, isoniazid (INH) and rifabutin (RFB). KGM/INH/RFB microparticles were produced by spray-drying to produce particles with suitable characteristics to deliver INH and RFB to the alveolar region. The KGM/INH/RFB microparticles possessed an aerodynamic diameter of approximately 3 µm, meeting the requirement of a therapy targeted to alveolar macrophages. Moreover, KGM microparticles exhibited suitable geometric size (2.24 µm) and shape (spherical) to be phagocytosed to deliver drugs to infected macrophages. INH and RFB were associated with KGM microparticles with efficiencies of 91% and 74%, respectively. Similar in vitro release profiles were observed for both drugs in simulated lung fluid (SLF) replicating the lining fluid composition found in human alveoli.