Laronidase-loaded liposomes reach the brain and other hard-to-treat organs after noninvasive nasal administration

• Published in: International journal of pharmaceutics Vol. 660; p. 124355
• Main Authors: Schuh, Roselena Silvestri, Franceschi, Eduarda Piovesan, Brum, Bruna Brazeiro, Fachel, Flávia Nathiely Silveira, Poletto, Édina, Vera, Luisa Natália Pimentel, Santos, Hallana Souza, Medeiros-Neves, Bruna, Monteagudo de Barros, Vinicius, Helena da Rosa Paz, Ana, Baldo, Guilherme, Matte, Ursula, Giugliani, Roberto, Ferreira Teixeira, Helder
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20-07-2024
• Subjects: Enzyme replacement therapy; Laronidase; Liposome; Mucopolysaccharidosis type I; Nasal route; Mucopolysaccharidosis type I; Liposome; Laronidase; Nasal route; Enzyme replacement therapy
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124355

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•Liposomal laronidase formulation was successfully developed.•Laronidase-loaded liposomes promoted an increase in enzyme activity in vitro.•Formulation was delivered through nasal route to MPS I mice.•Laronidase-loaded liposomes increased enzyme activity in all organs including brain.
Mucopolysaccharidosis type I (MPS I) is caused by a lack of the lysosomal enzyme α-L-iduronidase (IDUA), responsible for the degradation of the glycosaminoglycans (GAGs) dermatan and heparan sulfate, leading to multisystemic signs and symptoms. Enzyme replacement therapy (ERT) is a treatment that consists of weekly intravenous administrations of laronidase, a recombinant version of IDUA. However, ERT has limited access to certain tissues, such as bone, cartilage, and brain, and laronidase fails to trespass the BBB. In this sense, this study reports the development and characterization of laronidase-loaded liposomes for the treatment of MPS I mice. Liposomal complexes were obtained by the thin film formation method followed by microfluidization. The main characterization results showed mean vesicle size of 103.0 ± 3.3 nm, monodisperse populations of vesicles, zeta potential around + 30.0 ± 2.1 mV, and mucoadhesion strength of 5.69 ± 0.14 mN. Treatment of MPS I mice fibroblasts showed significant increase in enzyme activity. Nasal administration of complexes to MPS I mice resulted in significant increase in laronidase activity in the brain cortex, heart, lungs, kidneys, eyes, and serum. The overall results demonstrate the feasibility of nasal administration of laronidase-loaded liposomes to deliver enzyme in difficult-to-reach tissues, circumventing ERT issues and bringing hope as a potential treatment for MPS I.