Multivesicular liposomes for sustained release of bevacizumab in treating laser-induced choroidal neovascularization

Abstract

Bevacizumab is an anti-vascular endothelial growth factor drug that can be used to treat choroidal neovascularization (CNV). Bevacizumab-loaded multivesicular liposomes (Bev-MVLs) have been designed and developed to increase the intravitreal retention time of bevacizumab and reduce the number of injection times. In this study, Bev-MVLs with high encapsulation efficiency were prepared by double emulsification technique, and antibody activity was determined. The results revealed that 10% of human serum albumin (HSA) could preserve the activity of bevacizumab. In vitro release of Bev-MVLs appeared to be in a more sustained manner, the underlying mechanisms of Bev-MVLs indicated that bevacizumab was released from MVLs through diffusion and erosion. Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that bevacizumab could retain its structural integrity after being released from MVLs in vitro. In vivo imaging was used to evaluate the retention time of antibody in rat eyes, while pharmacokinetic analysis was performed on rabbit eyes. These results indicated that Bev-MVLs exhibited sustained release effects as compared to bevacizumab solution (Bev-S). Bev-MVLs could effectively inhibit the thickness of CNV lesion as compared to Bev-S at 28 days after treatment. Furthermore, these data suggest that Bev-MVLs are biologically feasible to increase the retention time of bevacizumab in vitreous humor. This novel Bev-MVLs may therefore serve as a promising sustained release drug delivery system for the treatment of CNV.

Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

“…Various liposome-based systems, when administered intravitreally, have been proven to allow sustained release of anti-VEGF for more than 1 month in animal models with good biocompatibility [65,68]. Mu et al have devised a multi-vesicular liposome comprised of a 95:5 ratio of aqueous component to lipid component, allowing a high encapsulation efficiency [65]. This allows the liposome platform to act as a depot for prolonged released of anti-VEGF.…”

Injectable Lipid-Based Depot Formulations: Where Do We Stand?

“…After successfully encapsulating small molecules, attention was drawn to the use of this delivery system for biomacromolecules. MVLs loaded with bevacizumab were used for the treatment of choroidal neovascularization, resulting in a prolonged intravitreal retention time of bevacizumab and consequently in a reduced number of intraocular injections [58]. Becavizumab-MVLs turned out to be superior to plain bevacizumab solution with respect to the effective inhibition of the thickness of the choroidal neovascularization lesion at 28 days after treatment.…”

“…Overview of different approaches using liposomal systems like large unilamellar liposomes (a), multivesicular liposomes (c), liposomes with different coatings creating core-shell-systems (b), or the embedding of liposomes in gels (d). (a) Reprinted from[55]; (b) Reprinted from[56] and (d) reprinted from[57] with permission from Elsevier; (c) Adapted from[50,58].…”

Photoimmunotherapy of Ovarian Cancer: A Unique Niche in the Management of Advanced Disease

“…Targeting and inactivation of intracellular targets remain a major challenge. As demonstrated in the study by Rahmanzadeh et al [129] and others [153,154], this could be achieved by delivering PICs intracellularly through nanoconstructs or PCI (as discussed in Section 4.4). As patients with high Ki67 expression respond better to first-line chemotherapy treatments [155], the targeted inactivation of Ki67 provides an alternative option for diagnostic and therapeutic applications.…”