Nanostructured lipid carriers-loaded dry powder inhaler for pulmonary delivery of amphotericin B in treatment of allergic bronchopulmonary aspergillosis.

Amphotericin B (AmB) is used to treat Allergic Bronchopulmonary Aspergillosis (ABPA) caused by Aspergillus fumigatus. AmB is available in oral and injectable forms but has limitations, resulting in low levels of AmB in the lungs. We formulated AmB using Nanostuctured Lipid Carriers (NLCs) and Dry Powder Inhaler (DPI) systems to improve the effectiveness of AmB delivery to the lungs. Oleic acid and Compritol® 888 ATO were used as liquid lipid and solid lipid materials for the preparation of NLCs. Characterization tests were conducted to determine the best formula, followed by in vivo pharmacokinetic studies. Characterization results of NLCs-AmB showed that AmB was encapsulated in NLCs in high amounts (21.37 %), with a particle size of 199.95 ± 18.97 nm. This value is better than NLCs-AmB 1 and NLCs-AmB 2. In vitro study showed the release of AmB from NLCs-AmB was 94.38 ± 5.68 %, while pure AmB was only 11.43 ± 1.83 %. Characterization of NLC-AmB-DPI showed good flow properties for NLCs-AmB-DPI 3, supporting delivery to the lungs. In vivo pharmacokinetic studies resulted in a high concentration in the lungs of 7.33 ± 0.56 µg/mL. Overall, this study offers proof-of-concept that the developed NLCs-AmB-DPI are good, safe, and can be used as an alternative for AmB delivery to the lungs, especially in the treatment of ABPA.