Human serum albumin nanoparticles for ocular delivery of bevacizumab

• Published in: International journal of pharmaceutics 2018-04, Vol.541 (1-2), p.214-223
• Main Authors: Luis de Redín, Inés, Boiero, Carolina, Martínez-Ohárriz, María Cristina, Agüeros, Maite, Ramos, Rocío, Peñuelas, Iván, Allemandi, Daniel, Llabot, Juan M., Irache, Juan M.
• Format: Article
• Language: English
• Subjects: Bevacizumab; Controlled release; Desolvation; Human serum albumin; Nanoparticles; Ocular delivery
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2018.02.003

[Display omitted] Bevacizumab-loaded nanoparticles (B-NP) were prepared by a desolvation process followed by freeze-drying, without any chemical, physical or enzymatic cross-linkage. Compared with typical HSA nanoparticles cross-linked with glutaraldehyde (B-NP-GLU), B-NP displayed a significantly higher mean size (310 nm vs. 180 nm) and a lower negative zeta potential (−15 mV vs. −36 mV). On the contrary, B-NP displayed a high payload of approximately 13% when measured by a specific ELISA, whereas B-NP-GLU presented a very low bevacizumab loading (0.1 μg/mg). These results could be related to the inactivation of bevacizumab after reacting with glutaraldehyde. From B-NP, bevacizumab was released following an initial burst effect, proceeded by a continuous release of bevacizumab at a rate of 6 μg/h. Cytotoxicity studies in ARPE cells were carried out at a single dose up to 72 h and with repeated doses over a 5-day period. Neither bevacizumab nor B-NP altered cell viability even when repeated doses were used. Finally, B-NP were labeled with 99mTc and administered as eye drops in rats. 99mTc-B-NP remained in the eye for at least 4 h while 99mTc-HSA was rapidly drained from the administration point. In summary, HSA nanoparticles may be an appropriate candidate for ocular delivery of bevacizumab.