Development and characterization of novel carrier gel core liposomes based transmission blocking malaria vaccine Shailja Tiwari a , Amit K. Goyal a , Neeraj Mishra a , Kapil Khatri a , Bhuvaneshwar Vaidya a , Abhinav Mehta a , Yimin Wu b , Suresh P. Vyas a, ⁎ a Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar, MP 470003, India b Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, United States abstract article info Article history: Received 26 March 2009 Accepted 4 August 2009 Available online 15 August 2009 Keywords: CpGODN Gel core liposomes Pfs25 Vaccine adjuvant Poly acrylic acid The aim of present work was to investigate the potential utility of novel carrier gel core liposomes for intramuscular delivery of transmission blocking malaria antigen Pfs25 and to evaluate the effect of co- administration of vaccine adjuvant CpGODN on immune enhancement of recombinant protein antigen Pfs25. In the present work we have prepared gel core liposomes containing core of biocompatible polymer poly acrylic acid in phospholipid bilayer by reverse phase evaporation method and characterized for various in vitro parameters. In process stability of the encapsulated antigen was evaluated by SDS-PAGE followed by western blotting. The immune stimulating ability was studied by measuring anti-Pfs25 antibody titer in serum of Balb/c mice following intramuscular administration of various formulations. A Significant and perdurable immune responses was obtained after intramuscular administration of gel core liposomes encapsulated Pfs25 as compared to Pfs25 loaded conventional liposomes. Moreover co-administration of CpGODN in liposomes (conventional and gel core) was found to further increase the immunogenicity of vaccine. The result indicates high potential of gel core liposomes for their use as a carrier adjuvant for intramuscular delivery of recombinant antigen Pfs25 based transmission blocking malaria vaccine. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Malaria is one of the most prevalent and devastating diseases throughout the world. It is responsible for 300 million clinical cases and 1.3 million deaths per year and one third of the human population lives in the areas that are infested with disease [1]. Malaria is caused by the parasite Plasmodium and four species of it falciparum, vivax, ovale and malariae are known to cause disease in human being in which falciparum is the most prevalent. Though this disease can be controlled by chemotherapeutic drugs but the development of drug resistance parasite and also insecticide resistance in its vector mosquito anopheles emphasizes urgent need for the development of a successful malaria vaccine. Although several antigenic candidate expressed on the surface of the parasite have been identified and tested but a successful vaccine is still a big challenge for immunologists [2]. Since the protozoan parasite plasmodium completes its life cycle in two host human being and mosquito, even in one host the parasite exists in several different forms [3].The low immunogenicity of antigenic candidate and toxicity of immunological adjuvant further aid the problem [4]. In recent years the transdisciplinary interest in novel carrier (liposomes, microparticle, bilosoames, nanoparticles etc.) as platform for the delivery of antigens and/or adjuvants has been steadily increasing [5]. The administration of novel carriers as vaccine delivery systems is not only suggested for protein antigens, but also for subunit vaccines and plasmid DNA or RNA based vaccines that encode antigens [6,7]. When an antigen is associated with particulates a stronger immune response as compared to soluble antigen is elicited [8]. An attractive motif for this approach is the postulate that par- ticulate delivery systems may mimic pathogens that are commonly recognized, phagocytosed and processed by professional antigen- presenting cells (APC). APC represent the foremost sentinels of the immune system. Their encounter with novel carriers activates them to migrate to lymph nodes where they present the antigen to cells of immune system in order to trigger an associated immune response [8,9]. It is commonly accepted that this activation would be most efficient when the molecular topology of the microparticulates is designed according to so-called pathogen-associated molecular patterns (PAMPs). PAMPs represent small molecular sequences which are consistently found on pathogens. APC recognize PAMPS by toll-like receptors and other pattern recognition receptors [10]. PAMPs include lipospolysaccharide, lipoteichoic acid from gram positive bacteria, peptidoglycans, and nucleic acid variants normally Journal of Controlled Release 140 (2009) 157–165 ⁎ Corresponding author. Tel./fax: +91 7582 265525. E-mail address: vyas_sp@rediffmail.com (S.P. Vyas). NANOMEDICINE 0168-3659/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jconrel.2009.08.004 Contents lists available at ScienceDirect Journal of Controlled Release journal homepage: www.elsevier.com/locate/jconrel