Transport of stavudine, delavirdine, and saquinavir across the blood-brain barrier by polybutylcyanoacrylate, methylmethacrylate-sulfopropylmethacrylate, and solid lipid nanoparticles.

摘要

Permeability of the anti-human immunodeficiency virus (HIV) agents, including stavudine (D4T), delavirdine (DLV), and saquinavir (SQV), across the in vitro blood-brain barrier (BBB) was studied. Here, the anti-HIV agents were incorporated with polybutylcyanoacrylate (PBCA) nanoparticles (NPs), methylmethacrylate-sulfopropylmethacrylate (MMA-SPM) NPs, and solid lipid nanoparticles (SLNs). Transport of the anti-HIV agents across BBB is a key factor in their applications to the therapy of the acquired immunodeficiency syndrome (AIDS). Experimental results revealed that the drug order of the loading efficiency (LE) on PBCA and MMA-SPM was D4T>DLV>SQV. For the entrapment efficiency (EE) in SLNs, this order was reversed. Also, LE of D4T on MMA-SPM was larger than that on PBCA; however, the reverse was true for DLV and SQV. As the particle size increased, LE decreased and EE increased. For a fixed drug carrier, an increase in the particle size yielded a decrease in the BBB permeability coefficient of the anti-HIV agents. Moreover, enhancement in the BBB permeability was on the carrier order of PBCA>MMA-SPM>SLNs for D4T, and for DLV and SQV, the order became PBCA>SLNs>MMA-SPM. PBCA, MMA-SPM, and SLNs were efficacious carriers of D4T, DLV, and SQV to meliorate BBB permeability by 3-16 folds, indicating the clinical potential of the present NP formulations for the AIDS treatment.