Methylmethacrylate–sulfopropylmethacrylate nanoparticles with surface RMP-7 for targeting delivery of antiretroviral drugs across the blood–brain barrier

This study investigates the capability of methylmethacrylate–sulfopropylmethacrylate (MMA–SPM) nanoparticles (NPs) with grafted RMP-7 (RMP-7/MMA–SPM NPs) to deliver stavudine (D4T), delavirdine (DLV), and saquinavir (SQV) across the blood–brain barrier (BBB). The permeability coefficients of the three drugs across the BBB were evaluated by a co-culture model containing human brain-microvascular endothelial cells and human astrocytes. An increase in the concentration of ammonium persulfate (APS), the polymerization initiator, enhanced the particle size of drug-loaded RMP-7/MMA–SPM NPs. When the concentration of APS was 0.6%, the average particle diameter was smaller than 50 nm. These spherical drug carriers were uniform in size and displayed a dominant topography of discrete hillocks and deep pits in deposited film. Smaller RMP-7/MMA–SPM NPs yielded a larger drug loading efficiency. The order of drug in the loading efficiency and in the particle uptake was, respectively, D4T > DLV > SQV and D4T > SQV > DLV. Endocytosis of RMP-7/MMA–SPM NPs and tight junction mediation can improve the permeability of D4T, DLV, and SQV across the BBB.

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► RMP-7/MMA–SPM NPs are spherical particles with uniform size.
► Smaller RMP-7/MMA–SPM NPs yield a larger loading efficiency of D4T, DLV and SQV.
► The order of drug in particle uptake by HBMECs is D4T > SQV > DLV.
► RMP-7/MMA–SPM NPs mediates tight junction opening for drug delivery.
► Endocytosis of RMP-7/MMA–SPM NPs improves the drug permeability across the BBB.