1. Laronidase-loaded liposomes reach the brain and other hard-to-treat organs after noninvasive nasal administration.
- Author
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Schuh RS, Franceschi EP, Brum BB, Fachel FNS, Poletto É, Vera LNP, Santos HS, Medeiros-Neves B, Monteagudo de Barros V, Helena da Rosa Paz A, Baldo G, Matte U, Giugliani R, and Ferreira Teixeira H
- Subjects
- Animals, Mice, Tissue Distribution, Fibroblasts drug effects, Male, Mice, Inbred C57BL, Liposomes, Iduronidase administration & dosage, Mucopolysaccharidosis I drug therapy, Administration, Intranasal, Brain metabolism, Brain drug effects, Enzyme Replacement Therapy methods
- Abstract
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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Roselena Silvestri Schuh has patent #BR 1020200049887 pending. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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