Preparation of intravenous stealthy acyclovir nanoparticles with increased mean residence time

Abstract

A major cause of thromboplebitis, during acyclovir (ACV) parenteral administration is the high pH of its reconstituted solution (pH 11). Its plasma half life is 2.5 h, requiring repeated administration which may result in excess of drug solubility leading to possible renal damage and acute renal failure. The present study reports the efficiency of stealthy ACV nanoparticles (NPs) to increase the mean residence time of the drug 29 times. It caused a marked decrease in thrombophlebitis when injected into rabbit's ear vein. The polymers used were (Poly lactic acid, polylactic-co-glycolic (PLGA) 85/15, PLGA 75/25, PLGA 50/50). Particles were evaluated for their encapsulation efficiency, morphology, particle size and size distribution, zeta potential, and in vitro drug release. Small NPs (280-300 nm) with 60% drug release after 48 h were obtained. Among the block copolymer used, poloxamer 407 was of superior coating properties with a coat thickness in the range of 1.5-8.3 nm and a decreased surface charge.

Fig. 1

TEM photomicrographs of ACV-loaded NPs prepared by SESD (×150,000)

Fig. 2

Plots for the main effect of the different factors: a Polymer type on particle size. b Surfactant type on particle size. c Polymer type on EE%. d Surfactant type on EE%

Fig. 3

Effect of surfactant type on zeta potential

Fig. 4

Release profile of ACV-NPs prepared using 1% Tween 80 and 1% poloxamer 407

Fig. 5

TEM photomicrographs of 75/25 PLGA ACV NPs using 1% tween 80 and coated with poloxamer 407

Fig. 6

DSC thermograms during heating from room temperature to 80°C in the first run and during heating from 0°C to 300°C in the second run. a ACV. b Polymer. c Unloaded NPs. d Loaded NPs

Fig. 7

Mean plasma concentrations—time profiles of ACV from different formulas after i.v. administration