Physiological neutral pH drives a gradual lamellar-to-reverse cubic-to-reverse hexagonal phase transition in phytantriol-based nanoparticles.

Dispersed systems of bicontinuous cubic phases, called cubosomes, show a drug release rate faster than those obtained using other liquid-crystalline phases. To minimize side effects associated with the accelerated release of incorporated drugs, compounds may be added in the dispersions to produce systems of slow initial release and then fast release only in the desired action region. This paper addresses the addition of 10.0% (w/w) of decyl betainate chloride (DBC), a cleavable surfactant, into phytantriol/Pluronic-based dispersions to generate lamellar-to-cubic-to-hexagonal phase transitions. Small-angle X-ray scattering (SAXS) was used to analyze the mesophases obtained with the addition of DBC and pH variation. Transmission electron microscopy (TEM) images confirmed the presence of niosomes after the addition of DBC. The niosomes formed in these systems are pH-responsive with lamellar-to-hexosomes transitions at pH ≥ 7.4. The system investigated herein is gastro-resistant presenting potential therapeutic role for controlled release of drugs in neutral or alkaline environments of the organism.

Monoolein-based nanoparticles for drug delivery to the central nervous system: A platform for lysosomal storage disorder treatment.

Lysosomal Storage Disorders (LSDs) are characterized by an abnormal accumulation of substrates within the lysosome and comprise more than 50 genetic disorders with a frequency of 1:5000 live births. Nanotechnology may be a promising way to circumvent the drawbacks of the current therapies for lysosomal diseases. The blood circulation time and bioavailability of the enzymes or drugs could be improved by inserting them in nanocarriers, which could decrease and/or avoid the need of frequent intravenous infusions along with the minimization or elimination of associated immunogenic responses. Considering the exposed, we aimed to build monoolein-based nanoparticles stabilized by polysorbate 80 as a smart platform able to reach the central nervous system (CNS) to deliver drugs or enzymes inside lysosomes. We developed and characterized the nanoparticles by dynamic light scattering (DLS), small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (Cryo-TEM). The nanoparticles showed a diameter of 115 nm, which is compatible with in vivo application. The SAXS patterns of the formulations displayed a single broad correlation peak that was fitted to the Teubner-Strey model confirming that disordered bicontinuous structures were obtained. Cryo-TEM images corroborated this finding and showed nanoparticles with size values that are similar to those determined by DLS. Furthermore, the nanoparticles did not present cytotoxicity when they were incubated with human fibroblasts, and demonstrated hemolytic activity proportional to the negative control, proving to be safe for parenteral administration. Through the use of a fluorescent dye to track the nanoparticles inside the cell, we demonstrated that they reached lysosomes after 1 h of treatment. More interestingly, the fluorescent dye was detected in the CNS of mice just after 3 h of treatment. The nanoparticles show great potential to improve the treatment of LSDs with brain impairment, acting as a smart platform to targeted delivery of drugs or enzymes.