title: Oral delivery of microparticles containing plasmid DNA encoding hepatitis-B surface antigen.
abstract: The role of albumin-based chitosan microparticles on enhancing immune response of plasmid DNA (pDNA) to hepatitis-B surface antigen (HBsAg) vaccine after oral administration was investigated in mice. The pDNA encoding HBsAg was entrapped in albumin microparticles using a one-step spray drying technique optimized in our laboratory. The encapsulated particles were also characterized in vitro for their shape, size, encapsulation efficiency, content, and stability. Albumin microparticles could protect the DNA from nuclease degradation as confirmed in our agarose gel study. Further immune modulating effect was studied in our formulation by measuring IgG antibodies in serum as well as IgA antibodies in fecal extracts. The mice were immunized with a prime dose of 100 μg of pDNA in microparticle formulations with and without interleukins biweekly until week 7 followed by a booster dose of equivalent strength on week 33 to compare the response with the subcutaneous group. The oral immunization with the pDNA to HBsAg microparticles gave significantly higher titer level of both sIgA and IgG at week 9 and 34, respectively, in oral vaccine with interleukins group when compared with the subcutaneous group. Thus, we observed an augmentation of both humoral and cellular immune responses for prolonged periods after immunization.
authors.affiliation: Encompass Pharmaceutical Services Inc, Norcross, GA, USA.
authors.forename: Tuhin
authors.initials: T
authors.lastname: Bhowmik
authors.forename: Bernadette
authors.initials: B
authors.lastname: D'Souza
authors.forename: Mohammad N
authors.initials: MN
authors.lastname: Uddin
authors.forename: Martin J
authors.initials: MJ
authors.lastname: D'Souza
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D004587:Electrophoresis, Agar Gel; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D010957:Plasmids; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013499:Surface Properties; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity
chemical_list: D004337:Drug Carriers; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D012710:Serum Albumin, Bovine; D004247:DNA; D048271:Chitosan