Astaxanthin-Loaded Stealth Lipid Nanoparticles (AST-SSLN) as Potential Carriers for the Treatment of Alzheimer’s Disease: Formulation Development and Optimization

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with marked oxidative stress at the level of the brain. Recent studies indicate that increasing the antioxidant capacity could represent a very promising therapeutic strategy for AD treatment. Astaxanthin (AST), a powerful natural antioxidant, could be a good candidate for AD treatment, although its use in clinical practice is compromised by its high instability. In order to overcome this limit, our attention focused on the development of innovative AST-loaded stealth lipid nanoparticles (AST-SSLNs) able to improve AST bioavailability in the brain. AST-SSLNs prepared by solvent-diffusion technique showed technological parameters suitable for parenteral administration (<200 nm). Formulated nanosystems were characterized by calorimetric studies, while their toxicological profile was evaluated by the MTT assay on the stem cell line OECs (Olfactory Ensheathing Cells). Furthemore, the protective effect of the nanocarriers was assessed by a long-term stability study and a UV stability assay confirming that the lipid shell of the nanocarriers was able to preserve AST concentration in the formulation. SSLNs were also capable of preserving AST’s antioxidant capacity as demonstrated in the oxygen radical absorbance capacity (ORAC) assay. In conclusion, these preliminary studies outline that SSLNs could be regarded as promising carriers for systemic administration of compounds such as AST aimed at AD treatment.

Lipid Nanoparticles Traverse Non-Corneal Path to Reach the Posterior Eye Segment: In Vivo Evidence

“…LN-ODAF were prepared by the solvent-diffusion technique, which proved to be a valid and highly reproducible method for this compound, minimizing the use of organic solvent, which might cause toxicity concerns if residues of it remain [ 22 , 23 ]. Preliminary studies have been directed to establish the best concentration of ODAF to be used in order to obtain nanotechnological parameters suitable for ocular administration.…”

“…LN-ODAF were prepared by a solvent-diffusion technique [ 22 ], using ODAF as the lipid phase and Lutrol F68 ® (Poloxamer 188) as the surfactant.…”

Chronic Stress and Oxidative Stress as Common Factors of the Pathogenesis of Depression and Alzheimer’s Disease: The Role of Antioxidants in Prevention and Treatment

“…Astaxanthin may also be important in the prevention of cardiac disease. It also has anti-aging and neuroprotective effects [ 218 , 219 ] and has the ability to reduce ischemic brain injury and may be used in pretreatment for stroke [ 220 ]. The antioxidant and anti-inflammatory activity combined with the ability to pass through the BBB makes astaxanthin a promising substance that may be applied in neurodegenerative diseases.…”

“…The antioxidant and anti-inflammatory activity combined with the ability to pass through the BBB makes astaxanthin a promising substance that may be applied in neurodegenerative diseases. Several previous studies clearly indicate that astaxanthin is able to form hydrogen bonds and van der Waals interactions with Aβ and prevent its accumulation and protect hippocampal cells from the deleterious effects of Aβ [ 219 , 221 ]. The unsaturated bonds in its structure limit its therapeutic use due to its instability and susceptibility to oxidation and photooxidation reactions.…”

“…Surface stabilization with surfactant (polysorbate 80) helps to avoid opsonization by immune cells. The diameter of the nanoparticles was <200 nm for parenteral administration [ 219 ].…”