Cationic solid lipid nanoparticles with cholesterol‐mediated surface layer for transporting saquinavir to the brain

Abstract

Cholesterol-mediated cationic solid lipid nanoparticles (CSLNs) were formulated with esterquat 1 (EQ 1) and stearylamine as positively charged external layers on hydrophobic internal cores of cacao butter. These CSLNs were employed to deliver saquinavir (SQV) to the brain. The permeability of SQV across the blood-brain barrier (BBB) using SQV-loaded CSLNs (SQV-CSLNs) was estimated with an in vitro model of a monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes. The results revealed that the average diameter of SQV-CSLNs diminished when the weight percentage of cholesterol and EQ 1 increased. The morphological images indicated a uniform size of SQV-CSLNs with compact lipid structure. In addition, an increasing weight percentage of cholesterol and EQ 1 enhanced the zeta potential of SQV-CSLNs. The fluorescent staining demonstrated that HBMECs could internalize SQV-CSLNs. An increase in the weight percentage of cholesterol and EQ 1 also promoted the uptake of SQV-CSLNs by HBMECs. Moreover, a high content of cholesterol and EQ 1 in SQV-CSLNs increased the BBB permeability of SQV. The cholesterol-mediated SQV-CSLNs can be an efficacious drug delivery system for brain-targeting delivery of antiviral agents.

Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

“…Therefore, cholesterol mediated SQV-CSNLS can be more efficacious drug delivery system for brain targeting delivery of antiviral agents [232]. Layer-by-layer thin film of reduced graphene oxide and gold nanoparticles are used in laser-induced desorption/ionization mass spectrometry for effective detection and drug delivery [233]. Similarly, diketopiperazine-based motif is considered as a novel brain shuttle for the delivery of drugs with limited ability to cross the blood brain barrier [225, 234].…”

Conjugation of melanotransferrin antibody on solid lipid nanoparticles for mediating brain cancer malignancy

“…In addition, the chamber with HBMECs was filled with culture medium containing 0.025% (w/v) MA‐ETP‐SLNs in the humidified CO 2 incubator at 37°C for 5 h. The lipid phase composition of MA‐ETP‐SLNs tested for the permeability coefficient for etoposide was given in the eighth, tenth, and twelfth row of Table . The etoposide concentration in the chamber with HAs was monitored using the HPLC‐UV at 284 nm every 2 h . The culture medium of 20 μL was sampled and immediately compensated with fresh culture medium of 20 μL.…”

Harnessing nanostructured systems for improved treatment and prevention of HIV disease

“…The surfactant that resulted in the more positively charged SLN surface produced a stronger attraction between the cationic SLNs and HBMECs based on the electrical interaction energy between the NPs and the cells . HBMEC permeability was improved from 4.3 × 10 −6 cm/s to > 5.6 × 10 −6 cm/s by altering the lipid composition of the SLNs to have a higher weight percentage of cholesterol and cationic esterquat 1 . The use of cholesterol as one of the nonionic lipids in the cationic SLN is believed to improve BBB penetration via cholesterol receptor‐mediated transcytosis across the HBMECs .…”

“…HBMEC permeability was improved from 4.3 × 10 −6 cm/s to > 5.6 × 10 −6 cm/s by altering the lipid composition of the SLNs to have a higher weight percentage of cholesterol and cationic esterquat 1 . The use of cholesterol as one of the nonionic lipids in the cationic SLN is believed to improve BBB penetration via cholesterol receptor‐mediated transcytosis across the HBMECs . All of this suggests the highly tunable nature of SLN biodistribution via surfactant and composition alteration.…”