Mitochondria-Targeted Delivery Strategy of Dual-Loaded Liposomes for Alzheimer’s Disease Therapy

Abstract

Liposomes modified with tetradecyltriphenylphosphonium bromide with dual loading of α-tocopherol and donepezil hydrochloride were successfully designed for intranasal administration. Physicochemical characteristics of cationic liposomes such as the hydrodynamic diameter, zeta potential, and polydispersity index were within the range from 105 to 115 nm, from +10 to +23 mV, and from 0.1 to 0.2, respectively. In vitro release curves of donepezil hydrochloride were analyzed using the Korsmeyer–Peppas, Higuchi, First-Order, and Zero-Order kinetic models. Nanocontainers modified with cationic surfactant statistically better penetrate into the mitochondria of rat motoneurons. Imaging of rat brain slices revealed the penetration of nanocarriers into the brain. Experiments on transgenic mice with an Alzheimer’s disease model (APP/PS1) demonstrated that the intranasal administration of liposomes within 21 days resulted in enhanced learning abilities and a reduction in the formation rate of Aβ plaques in the entorhinal cortex and hippocampus of the brain.

Mitochondria-Targeted Lipid Nanoparticles Loaded with Rotenone as a New Approach for the Treatment of Oncological Diseases

“…Additionally, increasing the concentration of TPPB-n and IA-n(OH) in the lipid bilayer contributed to a slight increase in the liposome zeta potential (Figure S1c,d). After 2 months of storage, the zeta potential of the IA-n(OH) liposomes decreased, while the zeta potential of the TPPB-n liposomes, on the contrary, increased, which was also shown earlier [36]. In addition, for the liposomes modified with a surfactant with a tetradecyl tail, the lowest PdI values were observed for both homologous series.…”

“…Therefore, as an alternative, the noncovalent modification of nanocontainers can be used [29]. Modified liposomes can also be obtained by introducing a TPP group into phospholipids [30][31][32] or by the noncovalent modification of nanoparticles with TPP-containing amphiphilic derivatives [33][34][35][36][37]. The latter is achieved by a hydrophobic tail that anchors into the lipid bilayer, while TPP is located on the inner and outer liposome surface.…”

The application strategy of liposomes in organ targeting therapy

“…Additionally, current research has confirmed that, unlike traditional intravenous or intraperitoneal administration, alternative liposomal drug delivery methods, such as nasal administration (Figure 6d,g,h) (Abbas et al, 2021;Allegritti et al, 2023;Han et al, 2023;R. Li, Lu, et al, 2022;Vasileva et al, 2023;Yu et al, 2023) and meningeal lymphatic vessel (MLV) pathway administration (Liu, Gao, et al, 2023), allow liposomes loaded with therapeutic agents to penetrate the BBB and directly enter the brain. This approach further increases the concentration of drugs in the brain.…”

Blood–brain barrier disruption in dementia: Nano‐solutions as new treatment options

“…Additionally, Rompicherla et al (2021) showed nasal delivery of rivastigmine loaded liposomes (composed of soya lecithin and cholesterol) induced rapid drug absorption to target tissue, enhanced systemic bioavailability and half‐life as well as reversing memory deficit in both acute and chronic AD models (Rompicherla et al, 2021). Similarly, Vasileva et al (2023) found that cholesterol‐based liposomes modified with tetradecyltriphenylphosphonium bromide were efficient in dual loading of α‐tocopherol and donepezil hydrochloride for intranasal delivery. Upon delivery within transgenic AD mouse models, they observed a reduced number of Aβ plaques in the entorhinal cortex, dentate gyrus and CA1 region of the hippocampus, supporting their use as a AD therapeutics carrier.…”