Dual alginate-lipid nanocarriers as oral delivery systems for amphotericin B

Amphotericin B (AmB) is the first-choice drug to treat several fungal infections. However, due to its low solubility it can only be administrated intravenously. Nanostructured lipid carriers (NLC) have the ability to encapsulate hydrophobic drugs in an aqueous matrix, making them interesting for use in alternative drug delivery systems for AmB. Their combination with stimuli-sensitive polymers such as alginate can be used as a strategy to protect acid sensitive molecules from gastric acid. The proposal of this work was to develop a dual-strategy hydrogel/NLC delivery system for amphotericin B. NLCs were produced by high-pressure homogenization and their size and stability were assessed by dynamic light scattering and electron transmission microscopy. The NLCs presented low cytotoxicity and high selectivity at neutral pH. Alginate hydrogels were successfully produced by the ionic gelation method and characterized using optical microscopy. The hydrogels were tested for their pH-selectivity, cytotoxicity and drug delivery profile. Swelling degree and drug delivery profiles suggested that drug delivery is stimulated as the alginate particles swell and that NLC particles maintain their structure even after rehydration, indicating these systems can be used for oral delivery of AmB.