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

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.

Nanoencapsulation of Vaccinium ashei Leaf Extract in Eudragit® RS100-Based Nanoparticles Increases Its In Vitro Antioxidant and In Vivo Antidepressant-like Actions.

Depression is a major psychiatric disorder in Brazil and worldwide. Vaccinium ashei (V. ashei) leaves are cultivation by-products with high bioactive compound levels. Here, a hydroalcoholic extract of V. ashei leaves (HEV) was associated with Eudragit® RS100-based nanoparticles (NPHEV) to evaluate the in vitro antioxidant and in vivo antidepressant-like effects. Interfacial deposition of the preformed polymer method was used for NPHEV production. The formulations were evaluated regarding physicochemical characteristics, antioxidant activity (DPPH radical scavenging and oxygen radical absorbance capacity), and antidepressant-like action (1-25 mg/kg, single intragastric administration) assessed in forced swimming and tail suspension tests in male Balb-C mice. The NPHEV presented sizes in the nanometric range (144-206 nm), positive zeta potential values (8-15 mV), polydispersity index below 0.2, and pH in the acid range. The phenolic compound content was near the theoretical values, although the rutin presented higher encapsulation efficiency (~95%) than the chlorogenic acid (~60%). The nanoencapsulation improved the HEV antioxidant effect and antidepressant-like action by reducing the immobility time in both behavioral tests. Hence, Eudragit® RS100 nanoparticles containing HEV were successfully obtained and are a promising alternative to manage depression.