The protective effect of albumin on bevacizumab activity and stability in PLGA nanoparticles intended for retinal and choroidal neovascularization treatments.
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.
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Reyhaneh
R
Varshochian
Mahmood
M
Jeddi-Tehrani
Ahmad Reza
AR
Mahmoudi
Mohammad Reza
MR
Khoshayand
Fatemeh
F
Atyabi
Araz
A
Sabzevari
Mohammad Riazi
MR
Esfahani
Rassoul
R
Dinarvand
D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry* / Q000494:pharmacology; D000068258:Bevacizumab; D020256:Choroidal Neovascularization / Q000188:drug therapy; D004355:Drug Stability; D007074:Immunoglobulin G / Q000276:immunology; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D015861:Retinal Neovascularization / Q000188:drug therapy; D012709:Serum Albumin / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D012709:Serum Albumin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D000068258:Bevacizumab; D019344:Lactic Acid
Albumin; Bevacizumab; Monoclonal antibody stability; Ophthalmic drug delivery; PLGA nanoparticles