Curcumin-Loaded Mesoporous Silica Nanoparticles Dispersed in Thermo-Responsive Hydrogel as Potential Alzheimer Disease Therapy

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive and behavioral impairment. Curcumin-loaded mesoporous silica nanoparticles (MSN-CCM) can overcome the drawbacks related to the free curcumin (CCM) clinical application, such as water insolubility and low bioavailability, besides acting over the main causes associated to AD. A thermo-responsive hydrogel is an interesting approach for facilitating the administration of the nanosystem via a nasal route, as well as for overcoming mucociliary clearance mechanisms. In light of this, MSN-CCM were dispersed in the hydrogel and evaluated through in vitro and in vivo assays. The MSNs and MSN-CCM were successfully characterized by physicochemical analysis and a high value of the CCM encapsulation efficiency (EE%, 87.70 ± 0.05) was achieved. The designed thermo-responsive hydrogel (HG) was characterized by rheology, texture profile analysis, and ex vivo mucoadhesion, showing excellent mechanical and mucoadhesive properties. Ex vivo permeation studies of MSN-CCM and HG@MSN-CCM showed high permeation values (12.46 ± 1.08 and 28.40 ± 1.88 μg cm−2 of CCM, respectively) in porcine nasal mucosa. In vivo studies performed in a streptozotocin-induced AD model confirmed that HG@MSN-CCM reverted the cognitive deficit in mice, acting as a potential formulation in the treatment of AD.

The application of mesoporous silica nanoparticles as a drug delivery vehicle in oral disease treatment

“…However, the insolubility in water, limited bioavailability, and instability in the biological environment of curcumin hampered its therapeutic use. Recently, studies had focused on curcumin-loaded MSNs (Cur-MSNs) due to their abilities to overcome the mentioned constraints of curcumin with a high encapsulation efficiency, protecting curcumin from premature leakage and providing a controlled drug release ( Ribeiro et al., 2022 ). Numerous studies had been conducted to demonstrate both their effect on the infections and their use in cancer therapy.…”

Mesoporous Materials Make Hydrogels More Powerful in Biomedicine

“…However, its water insolubility, low bioavailability, and instability in the biological environment hampered its clinical application. Loading curcumin onto mesoporous silica in a hydrogel exhibited excellent mechanical properties and much higher penetration values in pig nose mucosa than free curcumin [ 109 ]. Colchicine was observed as a potential treatment for osteoarthritis.…”

Biomaterials-Enhanced Intranasal Delivery of Drugs as a Direct Route for Brain Targeting

“…To overcome these drawbacks, more complex pharmaceutical formulations could be exploited, based on hydrogels releasing drug-loaded nanoparticles. Both weakly muco-adhesive hydrogels, such as Poloxamer [ 98 , 99 ], and highly muco-adhesive hydrogels, such as chitosan, Poloxamer/gellan and Poloxamer/chitosan [ 100 , 101 , 102 , 103 , 104 ], have been proposed. Such formulations are collected and described in Table 4 .…”