Efficacy of ganciclovir-loaded nanoparticles in human cytomegalovirus (HCMV)-infected cells.
The use of albumin nanoparticles to enhance the antiviral activity of ganciclovir (GCV) while decreasing its intrinsic toxicity was evaluated in human fibroblasts. GCV was adsorbed onto preformed protein nanoparticles (Np A) or incubated with the albumin solution prior to the formation of nanoparticles (Np B) by a coacervation method. The antiviral efficacies in MRC-5 and CHN cells were assayed by plaque reduction assay and early antigen detection, with several MOI and time of drug addition (T0 and T48). Whatever cell line or assay tested, Np A is the most active formulation whereas the efficacy of Np B is similar to the ganciclovir conventional therapy. Moreover, the profile of the dose-activity curve of the drug as a function of MOI is not altered by the use of nanoparticles and the efficacy of all formulations improves when added at T48. On the other hand, Np B produces a decrease on the cytotoxicity of the free drug in non-infected cells. Both activity and cytotoxicity seem to be straight correlated to the drug internalisation by cells. Thus, Np A highly improves the drug uptake, whereas Np B leads to a similar drug internalisation than the free drug.
Merodio
Marta
M
Centro Galénico, Universidad de Navarra, Pamplona, Spain.
Espuelas
M Socorro
MS
Mirshahi
Massoud
M
Arnedo
Amaia
A
Irache
Juan Manuel
JM
D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003315:Cornea / Q000166:cytology / Q000187:drug effects / Q000821:virology*; D003587:Cytomegalovirus / Q000187:drug effects* / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage; D004339:Drug Compounding / Q000379:methods; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000821:virology; D015774:Ganciclovir / Q000494:pharmacology*; D006801:Humans; D036103:Nanotechnology; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000008:administration & dosage; D013997:Time Factors
D000998:Antiviral Agents; D004337:Drug Carriers; D012710:Serum Albumin, Bovine; D015774:Ganciclovir