Contents lists available at ScienceDirect International Immunopharmacology journal homepage: www.elsevier.com/locate/intimp Chylomicron mimicking solid lipid nanoemulsions encapsulated enteric minicapsules targeted to colon for immunization against hepatitis B Kantrol Kumar Sahu, Monika Kaurav, Ravi Shankar Pandey ⁎ SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur, CG 495009, India ARTICLEINFO Keywords: Hepatitis B Colonic immunization Eudragit coated enteric minicapsules Lyophilised HBsAg nanoparticles Mucosal immunity ABSTRACT The oral route is one of the most convenient routes for drug and/or vaccine delivery. Yet variable nature of gastrointestinal tract due to transient changes in pH, physiology, and fora throughout the gut together with hostile nature of peptide drugs/vaccines when given by this route results in limited success. Colon targeting is a recent area of interest for most of the research among which hard gelatin coated capsules is one such important and useful contrivance. The present study assesses the mucosal immunization with HBsAg loaded lyophilized nanoparticles delivered in the colonic region using enteric coated minicapsules. Designed minicapsules ofers better compliance and oral vaccine antigen delivery to the colonic region which involving mucosal exposure thus mimicking the natural pathogen entry in the body. The present study is an extension of our reported work where nanoparticles were administered to the colon through the rectal route. Lyophilized nanoparticles were char- acterized for particle size, in-vitro release and antigen integrity along with cell uptake study. Particles had ~241 ± 32 nm sizes, fattened yet spherical in morphology. Enteric coated minicapsules were evaluated for size, coating thickness, and dissolution profle. In-vivo immune response assured its immunogenic potential with profound IgG (485 ± 41 mIU/ml) and IgA (885 ± 126 mIU/ml) antibody production as compared to marketed recombinant hepatitis B antigen formulation (Gene Vac-B®) which induce IgG and IgA titer; 1027 ± 62 mIU/ml and 220 ± 11 mIU/ml respectively following well established immunization protocol. Former induced sig- nifcant mucosal immunity due to the involvement of Common Mucosal Immune System (CMIS). The study supports the workable novel approach for immune protection against hepatitis B. 1. Introduction Hepatitis B is a severe chronic viral liver disease caused by hepatitis B virus (HBV), transmits similarly to that of HIV but comparatively more infectious [1]. The disease threatens by the annual death rate of 887,000 with 4 million acute infections worldwide. Being as a major cause of liver cirrhosis and hepatocellular carcinoma, the disease infects over 257 million individuals worldwide [2] out of which 20–30% can later develop into liver cancer [3]. Global Burden of Disease study (2010) has ranked HBV infection as a tenth leading cause of death and kept it in a top public health priority [4]. Although its prevalence is declined due to parenteral marketed vaccines, most of the populations in developing countries have limited access to it [5]. The oral route is the most acceptable route for majority population due to its convenience, the possibility of self-administration, avoidance of technical personnel and sterile syringe and pain. The se- lected region of the gastrointestinal tract (g.i.t.), the colon is a growing area of interest for various vaccine formulations. Mucosal delivery of antigens such as a colonic region of g.i.t., stimulates the common mu- cosal immune system (CMIS) and thus induce strong antibodies pro- duction. Preclinical and clinical trials for colon targeting have been achieved by various routes and formulations in the last few decades; among which one such approach is an enteric coated capsule. In 1834, gelatin capsules were frst patented by Mr. Mothes (Paris) for masking the taste and odor of medicine as an edible container [6]. Although a wide range of advanced polymers for drug targeting is available, the importance of capsules retains as a fnal proof of drug delivery in intact form to the desired site of g.i.t. if coated with some special polymer. Polymer coated capsules are gaining importance not only for oral vaccination but also for the colonic administration of various new active ingredients [7]. The coating of capsules/drugs using Eudragit as an enteric polymer for colon delivery is widely accepted by which controls site of drug release and based on a combination of its diferent forms (L-100, S-100, RS, RL etc.). https://doi.org/10.1016/j.intimp.2018.11.041 Received 9 July 2018; Received in revised form 9 November 2018; Accepted 25 November 2018 ⁎ Corresponding author at: SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Koni, Bilaspur, Chhattisgarh 495009, India. E-mail address: ravishankarpandey2@redifmail.com (R.S. Pandey). International Immunopharmacology 66 (2019) 317–329 1567-5769/ © 2018 Published by Elsevier B.V. T