title: Vitamin B12 Grafted Layer-by-Layer Liposomes Bearing HBsAg Facilitate Oral Immunization: Effect of Modulated Biomechanical Properties.
abstract: Adhesion forces of nanoparticulate materials toward biological membrane are crucial for designing a delivery system for therapeutic molecules and vaccines. The present study aims to investigate the impact of surface roughness of the nanoparticulate system in oral delivery of antigen and its targeting to toward intestinal antigen presenting cells. To evaluate this hypothesis, layer-by-layer coated liposomes (LBL-Lipo) were fabricated using sodium alginate and Vitamin B12 conjugated Chitosan (VitB12-Chi) as anionic and cationic polyelectrolyte, respectively. Change in surface roughness was observed on changes in pH from gastric to intestinal conditions attributed to increase and decrease in charge density on VitB12-Chi. Surface roughness was measured in terms of root-mean-square measured by topographical analysis using atomic force microscopy. LBL-Lipo were further characterized for their size, zeta potential, and release behavior to evaluate the potential for oral vaccine delivery. In vitro cell uptake in macrophage cells (J-744) shows about 2- and 3.1-fold increased uptake of rough LBL-Lipo over smooth LBL-Lipo at 37 °C (endocytosis) and 4 °C (endocytosis inhibition) indicating improved biological interaction. Further in vivo immunization study revealed that prototype formulations were able to produce 4.8- and 3.3-fold higher IgG and IgA levels in serum and feces, respectively, in comparison to smooth LBL-Lipo.
authors.affiliation: Division of Pharmaceutics, Council of Scientific & Industrial Research-Central Drug Research Institute (CSIR-CDRI) , Lucknow 226031, India.|BioScience & Biotechnology Division, Banasthali Vidyapith , Banasthali, Rajasthan 304022, India.
authors.forename: Ashwni Kumar
authors.initials: AK
authors.lastname: Verma
authors.affiliation: Division of Pharmaceutics, Council of Scientific & Industrial Research-Central Drug Research Institute (CSIR-CDRI) , Lucknow 226031, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Division of Pharmaceutics, Council of Scientific & Industrial Research-Central Drug Research Institute (CSIR-CDRI) , Lucknow 226031, India.
authors.forename: Pramod
authors.initials: P
authors.lastname: Gupta
authors.affiliation: Division of Pharmaceutics, Council of Scientific & Industrial Research-Central Drug Research Institute (CSIR-CDRI) , Lucknow 226031, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Singodia
authors.affiliation: Division of Pharmaceutics, Council of Scientific & Industrial Research-Central Drug Research Institute (CSIR-CDRI) , Lucknow 226031, India.
authors.forename: Shaswat
authors.initials: S
authors.lastname: Kansal
authors.affiliation: BioScience & Biotechnology Division, Banasthali Vidyapith , Banasthali, Rajasthan 304022, India.
authors.forename: Veena
authors.initials: V
authors.lastname: Sharma
authors.affiliation: Division of Pharmaceutics, Council of Scientific & Industrial Research-Central Drug Research Institute (CSIR-CDRI) , Lucknow 226031, India.
authors.forename: Prabhat Ranjan
authors.initials: PR
authors.lastname: Mishra
mesh_terms: D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D020723:Glucuronic Acid / Q000737:chemistry; D019073:HT29 Cells; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology*; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007114:Immunization / Q000379:methods*; D008081:Liposomes / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D018625:Microscopy, Atomic Force; D014805:Vitamin B 12 / Q000737:chemistry*
chemical_list: D000464:Alginates; D006514:Hepatitis B Surface Antigens; D006603:Hexuronic Acids; D008081:Liposomes; D020723:Glucuronic Acid; D048271:Chitosan; D014805:Vitamin B 12
keywords: AFM; APCs; Peyer’s patches; Vitamin B12; biomechanical properties; mucus penetration