No abstract

Human serum albumin (HSA) nanoparticles (NP) were prepared by desolvation. Insulin or an anti-insulin receptor monoclonal antibody (29B4) were covalently coupled to the HSA NP, using the NHS-PEG-MAL-5000 crosslinker. Loperamide-loaded HSA NP with covalently bound insulin or the 29B4 antibodies induced significant antinociceptive effects in the tail-flick test in ICR (CD-1) mice after intravenous injection, demonstrating that insulin or these antibodies covalently coupled to HSA NP are able to transport loperamide across the blood-brain barrier (BBB) which it normally is unable to cross. Control loperamide-loaded HSA NP with immunoglobulin G antibodies yielded only marginal effects. The loperamide transport across the BBB using the NP with covalently attached insulin could be totally inhibited by the pretreatment with the antibody 29B4.

No abstract

The Gd-HSA nanoparticles have potential as MRI contrast agents. In particular, Gd-HSA-NP-Tf has a potential as a specific contrast agent for the brain, while the blood-brain barrier is still intact, as well as in the heart, liver, and skeletal muscle.

Different from regular small molecule contrast agents, nanoparticle-based contrast agents have a longer circulation time and can be modified with ligands to confer tissue-specific contrasting properties. We evaluated the tissue distribution of polymeric nanoparticles (NPs) prepared from human serum albumin (HSA), loaded with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) (Gd-HSA-NP), and coated with folic acid (FA) (Gd-HSA-NP-FA) in mice by magnetic resonance imaging (MRI). FA increases the affinity of the Gd-HSA-NP to FA receptor-expressing cells. Clinical 3 T MRI was used to evaluate the signal intensities in the different organs of mice injected with Gd-DTPA, Gd-HSA-NP, or Gd-HSA-NP-FA. Signal intensities were measured and standardized by calculating the signal to noise ratios. In general, the NP-based contrast agents provided stronger contrasting than Gd-DTPA. Gd-HSA-NP-FA provided a significant contrast enhancement (CE) in the brain (p  =  .0032), whereas Gd-DTPA or Gd-HSA-NP did not. All studied MRI contrast agents showed significant CE in the blood, kidney, and liver (p < .05). Gd-HSA-NP-FA elicited significantly higher CE in the blood than Gd-HSA-NP (p  =  .0069); Gd-HSA-NP and Gd-HSA-NP-FA did not show CE in skeletal muscle and gallbladder; Gd-HSA-NP, but not Gd-HSA-NP-FA, showed CE in the cardiac muscle. Gd-HSA-NP-FA has potential as an MRI contrast agent in the brain.