Physicochemical and Biological Evaluation of Bioadhesive Polymers for the Development of Intranasal Low Sialic Acid Erythropoietin Formulations

by A. Muñoz-Cernada, J. Cardentey-Fernández, Z. Pardo-Ruiz, D. Díaz-Sánchez, V. Montero-Alejo, I. Sosa-Testé, M. Fernández-Cervera, J.C. García-Rodríguez, and D. Amaro-González
Volume 13, Issue 1 (Spring 2014)

Low sialic acid erythropoietin (Neuro-EPO) is a nonerythropoietic molecule that shows neuroprotective activity in some rodent models for brain ischemia. One reason for poor absorption may be the rapid removal of the drug from the site of absorption by mucociliary clearance. For that reason, bioadhesive polymers are used to increase the residence time of the drug in the nasal cavity. The objective of the current study was to evaluate different bioadhesive polymers to identify Neuro-EPO formulations with characteristics suitable for nasal delivery. For this purpose, four different polymers: (1) hydroxypropyl methylcellulose (HPMC) F4M; (2) HPMC K4M; (3) Carbopol 974P; and (4) dextran 70 were assessed to define the appropriate concentration. The physicochemical evaluation of placebo formulations showed reductions in apparent viscosity, except with dextran 70. With dextran 70, the bioadhesive polymers interacted with other excipients such as buffers, isotonic agents, and antimicrobial preservatives. The decrease of apparent viscosity was observed significantly in the formulation with Carbopol 974P, which also showed the presence of instability. Formulations with Neuro-EPO and HPMC showed adequate physicochemical properties with the pH, isotonicity, and concentrations of protein by reverse-phase (RP) high-pressure liquid chromatography (HPLC), as expected. However, the formulation with dextran 70 showed chemical incompatibility, as evidenced by the reduction of protein concentration and purity. In the permanent unilateral ischemia model, a higher survival percentage was observed with formulations of HPMC F4M and HPMC K4M, evidenced by the analysis of neurology parameters. Both formulations were significantly different from their vehicle...

Citation:
Muñoz-Cernada A, Cardentey-Fernández J, Pardo-Ruiz Z, Díaz-Sánchez D, Montero-Alejo V, Sosa-Testé I, Fernández-Cervera M, García-Rodríguez JC, Amaro-González D. Physicochemical and Biological Evaluation of Bioadhesive Polymers for the Development of Intranasal Low Sialic Acid Erythropoietin Formulations. BioProcess J, 2014; 13(1): 23-31. http://dx.doi.org/10.12665/J131.Amaro-Gonzalez.

Posted online April 23, 2014.