The comparative study of some substances on release of bevacizumab from nanolipsome
Maryam Malakouti Nejad1 , Dina Morshedi1 *, Ali Reza Baradaran-Rafiei2 , Hassan Bardania3
- Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
- Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, No 23, Paydarfard-9th Boostan St., Pasdaran Ave, Tehran, Iran
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
Abstract: Bevacizumab (Avastin®), a vascular endothelial growth factor (VEGF)-targeting drug, is widely used as an off-label therapeutic agent to inhibit VEGF-dependent angiogenesis situations like age-related macular degeneration (AMD) and corneal neovascularization. To reduce the administration frequency and increase the protein's half-life, the drug was encapsulated in the nanoliposomes containing DPPC, cholesterol, and polyethyle glycol (PEG). Our study aimed to investigate the biocompatibility of the formulation and the effect of various substances towards the release behavior of the drug from nanoliposomes.
Methods: Nanoliposome containing bevacizumab (NLP-BVZ) was prepared using the thin-film evaporation method. By dynamic light scattering (DLS) and transmission electron microscopy (TEM) assays, characterization of the NLP-BVZ was performed in terms of size and shape. Afterward, for improved in vitro release of BVZ from NLP, the effect of SDS (0.05%), tween-20 (0.025%), triton X-100 (0.025%), and PEG 2000 (0.05%) was assessed for 42 days. Subsequently, to determine the biocompatibility of NLP-BVZ, the hemolysis assay was performed.
Results: with tween 20 (0.025%), the formulation exhibited in vitro release comprising continuous and sustained behavior (19.42 ± 1.71%).
PEG 2000 (0.005%) led to a burst, but not a long-term release of BVZ. An extremely small amount of the released drug was seen in the control without any substances (4.19 ± 1.54), similar to applying triton-X100. There was no sign of hemolysis in the case of NLP-BVZ, so the formulation was well tolerated, and it could be assigned, safe, and biocompatible for ocular drug delivery.
Conclusion: The release of the drug from nanoliposomal formulation could be improved by the addition of various surfactants and substances. Several excipients, like tween-20 and triton X-100, are widely used in biochemical applications. However, we showed that in the presence of tween-20 (0.025%), BVZ was released in a slow but continuous manner without burst release. They were so comparing other substances, tween 20, as an especially attractive nonionic, non-toxic, environmentally friendly, biocompatible, and commercially inexpensive surfactant could be considered as the preferred condition for extended-release of BVZ from NLP. In conclusion, these encouraging results propose the potential application of bevacizumab-loaded nanoliposomes as a means of intravitreal therapy for ocular angiogenesis diseases.
