Albumin nanoparticles improved the stability, nuclear accumulation and anticytomegaloviral activity of a phosphodiester oligonucleotide.
The goal of this study was to evaluate the potential of albumin nanoparticles as a delivery system for antisense oligonucleotides. Nanoparticles were prepared by a coacervation process and cross-linkage with glutaraldehyde. Phosphodiester (PO) and phosphorotioate (PS) oligonucleotides were either adsorbed on the surface of nanoparticles (PO-NPA and PS-NPA) or incorporated in the nanoparticle matrix (PO-NPB and PS-NPB). When PO-loaded nanoparticles were incubated with phosphodiesterase, only NPB was able to keep the oligonucleotide hybridization capability for at least 60 min. The antiviral activity was evaluated in MRC-5 fibroblasts infected with human cytomegalovirus at a MOI of 0.0035. Both PO nanoparticle formulations significantly increased the antiviral activity of free PO (P<0.001) and NPB showed slightly higher efficacies than NPA (P<0.05). On the other hand, PS exhibited significant higher activity than free PO (P<0.001), however, no significant differences were found between PS-nanoparticle and PO-nanoparticle formulations. These findings were well correlated with the intracellular distribution observed for fluorescent oligonucleotide-loaded albumin nanoparticles. Even these carriers delayed and decreased the uptake of PO by MRC-5 cells, they finally induced a diffused cytoplasmic distribution and major nuclear accumulation. In summary, albumin nanoparticles partially protected a PO against enzymatic degradation and improved their presence in the nucleus and thus, increased its efficiency.
Arnedo
A
A
Centro Galénico, Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, Irunlarrea 1, Ap. 177, 31080 Pamplona, Spain.
Irache
J M
JM
Merodio
M
M
Espuelas Millán
M S
MS
D000418:Albumins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003587:Cytomegalovirus / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D004355:Drug Stability; D006801:Humans; D036103:Nanotechnology / Q000379:methods*; D009841:Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010948:Viral Plaque Assay
D000418:Albumins; D000998:Antiviral Agents; D009841:Oligonucleotides