Intracellular delivery of saquinavir in biodegradable polymeric nanoparticles for HIV/AIDS.
OBJECTIVE
This study aims at developing poly(ethylene oxide)-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticulate system as an intracellular delivery vehicle for saquinavir, an anti-HIV protease inhibitor.


METHODS
Saquinavir-loaded PEO-PCL nanoparticles were prepared by a solvent displacement process. The formed nanoparticles were characterized for size, surface charge, and surface presence of PEO chains. Cellular uptake and distribution of the nanoparticle was examined in THP-1 human monocyte/macrophage (Mo/Mac) cell line. Intracellular saquinavir concentrations were measured as a function of dose and duration of incubation.


RESULTS
The PEO-PCL nanoparticles had a smooth surface and spherical shape and showed a relatively uniform size distribution with a mean particle diameter of approximately 200 nm. The surface presence of PEO chains was confirmed by an increase in the -C-O-(ether) signature of the C1s spectra in electron spectroscopy for chemical analysis. Rapid cellular uptake of rhodamine-123 encapsulated PEO-PCL nanoparticles was observed in THP-1 cells. Intracellular saquinavir concentrations when administered in the nanoparticle formulation were significantly higher than from aqueous solution.


CONCLUSIONS
This study shows that PEO-PCL nanoparticles provide a versatile platform for encapsulation of saquinavir and subsequent intracellular delivery in Mo/Mac cells.
Shah
Lipa K
LK
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, Massachusetts 02115, USA.
Amiji
Mansoor M
MM
D019380:Anti-HIV Agents / Q000008:administration & dosage*; D002460:Cell Line; D016503:Drug Delivery Systems; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D053758:Nanoparticles; D011091:Polyesters / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage; D019258:Saquinavir / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility
D019380:Anti-HIV Agents; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols; D019258:Saquinavir