Encapsulation of water-insoluble drugs in poly(butyl cyanoacrylate) nanoparticles.

Hydrophobic drugs, loperamide and paclitaxel, were loaded in poly(butyl cyanoacrylate) nanoparticles by polymerization of n-butyl-2-cyanoacrylate in aqueous-organic media in the presence of a drug. The particles were stabilized by dextran 70,000 and poloxamer 188 or by 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000] sodium salt. It was shown that in the presence of dichloromethane, methanol or ethanol the encapsulation efficiency of loperamide in the nanoparticles reached 80%. Loading of paclitaxel was efficient only in the presence of the lipid. The organic solvents did not significantly influence the nanoparticle morphology or their physicochemical parameters. Thus produced poly(butyl cyanoacrylate) nanoparticles enabled delivery of loperamide across the blood-brain barrier, which was evidenced by the drug analgesic effect evaluated by the tail-flick test.

Transferrin- and transferrin-receptor-antibody-modified nanoparticles enable drug delivery across the blood-brain barrier (BBB).

Human serum albumin (HSA) nanoparticles were manufactured by desolvation. Transferrin or transferrin receptor monoclonal antibodies (OX26 or R17217) were covalently coupled to the HSA nanoparticles using the NHS-PEG-MAL-5000 crosslinker. Loperamide was used as a model drug since it normally does not cross the blood-brain barrier (BBB) and was bound to the nanoparticles by adsorption. Loperamide-loaded HSA nanoparticles with covalently bound transferrin or the OX26 or R17217 antibodies induced significant anti-nociceptive effects in the tail-flick test in ICR (CD-1) mice after intravenous injection, demonstrating that transferrin or these antibodies covalently coupled to HSA nanoparticles are able to transport loperamide and possibly other drugs across the BBB. Control loperamide-loaded HSA nanoparticles with IgG2a antibodies yielded only marginal effects.

Covalent attachment of apolipoprotein A-I and apolipoprotein B-100 to albumin nanoparticles enables drug transport into the brain.

Apolipoprotein E3, A-I as well as B-100 were covalently attached to human serum albumin nanoparticles via the NHS-PEG-Mal 3400 linker. Loperamide as a model drug was bound to these nanoparticles, and the antinociceptive reaction of these preparations was recorded after intravenous injection in mice by the tail-flick test. After 15 min, all three nanoparticle preparations with the coupled apolipoproteins E3, A-I, and B-100 yielded considerable antinociceptive effects, which lasted over 1 h. The maximally possible effects [MPE] of these preparations amounted to 95%, 65%, and 50%, respectively, and were statistically different from the controls (p<0.02), whereas the loperamide solution achieved no effect. This result demonstrates that more than one mechanism is involved in the interaction of nanoparticles with the brain endothelial cells and the resulting delivery of drugs to the central nervous system.