title: Physicochemical and Preclinical Evaluation of a Novel Buccal Measles Vaccine.
abstract: The aim of this study is to develop an orally disintegrating film (ODF) containing a microparticulate measles vaccine formulation for buccal delivery. The measles vaccine microparticles were made with biocompatible and biodegradable bovine serum albumin (BSA) and processed by spray drying. These vaccine microparticles were incorporated in the ODF, consisting of Lycoat RS720®, Neosorb P60W® and Tween 80. The yield of the microparticles was approximately 85-95%, w/w. The mean size of the vaccine microparticles was 3.65 ± 1.89 μm and had a slightly negative surface charge of 32.65 ± 2.4 mV. The vaccine particles were nontoxic to normal cells at high concentrations (500 μg/2.5 × 105cells) of vaccine particles. There was a significant induction of innate immune response by vaccine microparticles which was observed in vitro when compared to blank microparticles (P < 0.05). The vaccine microparticles also significantly increased the antigen presentation and co-stimulatory molecules expression on antigen presenting cells, which is a prerequisite for Th1 and Th2 immune responses. When the ODF vaccine formulation was dosed in juvenile pigs, significantly higher antibody titers were observed after week 2, with a significant increase at week 4 and plateauing through week 6 comparative to naïve predose titers. The results suggest that the ODF measles vaccine formulation is a viable dosage form alternative to noninvasive immunization that may increase patient compliance and commercial distribution.
authors.affiliation: Vaccine Nanotechnology Laboratory, Department of Pharmaceutical Sciences, Mercer University, 3001 Mercer University Drive, Atlanta, GA, 30341, USA.
authors.forename: Rikhav P
authors.initials: RP
authors.lastname: Gala
authors.affiliation: Roquette America Inc, Geneva, IL, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Popescu
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Dr, West Lafayette, IN, 47906, USA. gknipp@purdue.edu.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Knipp
authors.affiliation: Purdue Translational Pharmacology of Bindley Biosciences, Purdue University, West Lafayette, IN, USA.
authors.forename: Robyn R
authors.initials: RR
authors.lastname: McCain
authors.affiliation: Vaccine Nanotechnology Laboratory, Department of Pharmaceutical Sciences, Mercer University, 3001 Mercer University Drive, Atlanta, GA, 30341, USA.
authors.forename: Ruhi V
authors.initials: RV
authors.lastname: Ubale
authors.affiliation: Department of Pharmaceutical Sciences, Union University School of Pharmacy, Jackson, TN, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Addo
authors.affiliation: Takeda Vaccine Business Unit, Bozeman, MT, USA.
authors.forename: Tuhin
authors.initials: T
authors.lastname: Bhowmik
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Dr, West Lafayette, IN, 47906, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Kulczar
authors.affiliation: Vaccine Nanotechnology Laboratory, Department of Pharmaceutical Sciences, Mercer University, 3001 Mercer University Drive, Atlanta, GA, 30341, USA. dsouza_mj@mercer.edu.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: D'Souza
mesh_terms: D000278:Administration, Buccal; D000284:Administration, Oral; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D007114:Immunization / Q000379:methods; D008458:Measles Vaccine / Q000008:administration & dosage* / Q000737:chemistry*; D051379:Mice; D008863:Microspheres; D009061:Mouth Mucosa / Q000378:metabolism*; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013552:Swine
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D008458:Measles Vaccine; D012710:Serum Albumin, Bovine
keywords: ODF; buccal delivery; measles; microparticle; pediatric; vaccine