The protective effect of albumin on bevacizumab activity and stability in PLGA nanoparticles intended for retinal and choroidal neovascularization treatments

• Published in: European journal of pharmaceutical sciences Vol. 50; no. 3-4; pp. 341 - 352
• Main Authors: Varshochian, Reyhaneh, Jeddi-Tehrani, Mahmood, Mahmoudi, Ahmad Reza, Khoshayand, Mohammad Reza, Atyabi, Fatemeh, Sabzevari, Araz, Esfahani, Mohammad Riazi, Dinarvand, Rassoul
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.11.2013
• Subjects: Albumin; Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - pharmacology; Animals; Antibodies, Monoclonal, Humanized - chemistry; Antibodies, Monoclonal, Humanized - pharmacology; Bevacizumab; Choroidal Neovascularization - drug therapy; Drug Stability; Immunoglobulin G - immunology; Lactic Acid - chemistry; Medicin och hälsovetenskap; Monoclonal antibody stability; Nanoparticles - chemistry; Ophthalmic drug delivery; PLGA nanoparticles; Polyglycolic Acid - chemistry; Rabbits; Retinal Neovascularization - drug therapy; Serum Albumin - chemistry; Vascular Endothelial Growth Factor A - metabolism; Vitreous Body - metabolism; Albumin; Ophthalmic drug delivery; Monoclonal antibody stability; PLGA nanoparticles; Bevacizumab
• ISSN: 0928-0987; 1879-0720; 1879-0720
• DOI: 10.1016/j.ejps.2013.07.014

The paper showed incorporation of albumin within the aqueous phase of primary emulsion in double emulsion method could protect bevacizumab from emulsification drawbacks during entrapment into PLGA nanoparticles. It has been assumed that albumins prevent bevacizumab interfacial-adsorption by competition with the antibody in occupying the interface as well as shielding bevacizumab and preventing its contact with hydrophobic phase. (A: bevacizumab w/o emulsion without stabilizer and B: bevacizumab w/o emulsion with albumin as stabilizer). The rapidly growing applications of antibody-based therapeutics requires novel approaches to develop efficient drug delivery systems in which biodegradable polymeric nanoparticles are amongst the best candidates. In the present study bevacizumab loaded PLGA nanoparticles were formulated by water-in-oil-in-water emulsion method. Protein inactivation and aggregation are the major drawbacks of this technique. Therefore protective ability of various stabilizers was studied during entrapment process. Probable changes in VEGF165 binding capability of bevacizumab was assayed by ELISA which portrays the antibody’s bio-efficiency. Probable breakage of bevacizumab and its secondary and tertiary structural integrity upon entrapment were analyzed by SDS–PAGE and circular dichroism spectroscopy, respectively. In vitro and ex vivo released bevacizumab from the prepared nanoparticles was also investigated. Results revealed that the protein interfacial adsorption is the foremost destabilizing factor in the double emulsion method and incorporation of appropriate concentrations of albumin could protect bevacizumab against entrapment stress. Ex vivo release results, in rabbit vitreous, indicated the ability of prepared nanoparticles in prolonged release of the active antibody. Consequently this approach was an attempt to achieve sustained release PLGA nanoparticle formulation with the aim of protecting integrity and performance of entrapped bevacizumab.