Polyethylene glycol (5,000) succinate conjugate of lopinavir and its associated toxicity using Danio rerio as a model organism

Lopinavir (LPV), a well-known drug administered in human immunodeficiency virus (HIV) infection, has shown limitation for pediatric treatment owing to poor aqueous solubility that gives rise to limited oral bioavailability and short plasma half-life (5–6 h). Polymers such as polyethylene glycol (PEG) have been used as drug carriers to improve their solubility. This study reports the preparation of polyethylene glycol (5,000) succinate (PEG–Suc–LPV) conjugate of LPV by the esterification method. The disappearance of the 3,395 cm(−1) (O–H stretch of COOH) band for Polyethylene glycol (5,000) succinate (PEG–Suc )confirms the formation ester linkage with the OH group of LPV which is also confirmed by (1)H NMR analysis. The XRD for the conjugate showed a broad, amorphous peak while pure PEG, Suc, LPV are crystalline. DSC analysis showed that the conjugate exhibited new broad and diffuse peaks, confirming that they did exist in an amorphous state as multiple complexes. The conjugate showed improved solubility and activity with reduced toxicity compared to pure LPV. The solubility of LPV increased significantly from 80 to 318 ppm. Furthermore, an aquatic toxicity test using Danio rerio showed that the conjugate had a lower LC(50) (60.8 ppm) when compared to the pure LPV drug LC(50) (6.42 ppm). These results suggest PEG–Suc conjugate of LPV as an efficient carrier for enhanced hydrophilicity and anti-HIV property of LPV.