title: An approach to a cold chain free oral cholera vaccine: in vitro and in vivo characterization of Vibrio cholerae gastro-resistant microparticles.
abstract: The present work describes the formulation of Eudragit(®) L30 D-55 microparticles (MP) alone or with mucoadhesive agents, alginate or Carbopol(®), as an approach for the development of an oral cholera vaccine. In the first part, a spray drying technique was optimized for microparticle elaboration, obtaining a microparticle size ranging from 7 to 9 μm with high encapsulation efficiencies. Moreover, gastro resistant properties and Vibrio cholerae (VC) antigenicity were maintained, but for Eudragit(®)-Carbopol(®) microparticles which showed low antigenicity values, ≈25%. Next, a stability study was performed following ICH Q1 A (R2) guidelines, i.e. 25°C-60% relative humidity (RH) for 12 months, and 30°C-65% RH and 40°C-75% RH for 6 months. Upon storage, microparticle size changed slightly, 1 μm for Eudragit(®)-alginate MPs and 0.36 μm for Eudragit(®)MP. However, gastro resistance and antigenicity values were kept in an acceptance range. In the third stage of this work, in vivo experiments were performed. The immune response evoked was measured by means of vibriocidal titer quantification, observing that Eudragit(®)-alginate MPs were able to induce stronger immune responses, comparable to the free VC. Therefore, microencapsulation of VC by spray drying could be proposed as an approach to a cold chain free and effective oral cholera vaccine.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country, School of Pharmacy, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pastor
authors.forename: A
authors.initials: A
authors.lastname: Esquisabel
authors.forename: A
authors.initials: A
authors.lastname: Talavera
authors.forename: G
authors.initials: G
authors.lastname: Año
authors.forename: S
authors.initials: S
authors.lastname: Fernández
authors.forename: B
authors.initials: B
authors.lastname: Cedré
authors.forename: J F
authors.initials: JF
authors.lastname: Infante
authors.forename: A
authors.initials: A
authors.lastname: Callicó
authors.forename: J L
authors.initials: JL
authors.lastname: Pedraz
mesh_terms: D000180:Acrylic Resins; D000284:Administration, Oral; D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D022121:Cholera Vaccines; D004355:Drug Stability; D004356:Drug Storage; D005260:Female; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry; D008689:Methacrylates / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D011145:Polyvinyls / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012034:Refrigeration; D015164:Vaccines, Inactivated; D014734:Vibrio cholerae
chemical_list: D000180:Acrylic Resins; D000464:Alginates; D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; C477852:Eudragit L 30 D-55; D006603:Hexuronic Acids; D008689:Methacrylates; D011108:Polymers; D011145:Polyvinyls; D015164:Vaccines, Inactivated; C006912:carboxypolymethylene; D020723:Glucuronic Acid