Investigation of lectinized liposomes as M-cell targeted carrier-adjuvant for mucosal immunization.
In the present investigation hepatitis B surface antigen (HBsAg) encapsulated liposomes were developed and coupled with Ulex europaeus agglutinin 1 (UEA-1) to increase transmucosal uptake by M-cells of the Peyer's patches. The liposomes were characterized for shape, size, polydispersity and encapsulation efficiency. Bovine submaxillary mucin (BSM) was used as a biological model for the in vitro determination of lectin activity and specificity. Dual staining technique was used to investigate targeting of lectinized liposomes to the M-cells. Anti-HBsAg IgG response in serum and anti-HBsAg sIgA level in various mucosal fluids was estimated by using ELISA, following oral immunization with lectinized and non-lectinized liposomes in Balb/c mice. Additionally, interleukin-2 (IL-2) and interferon-γ (IFN-γ) level in the spleen homogenates was determined. The results suggest that lectinized liposomes were successfully developed, exhibited increased activity with BSM as compared to non-lectinized liposomes and α-l-fucose specificity of the lectinized liposomes was also maintained. The lectinized liposomes were predominantly targeted to the M-cells. The serum anti-HBsAg IgG titre obtained after 3 consecutive days oral immunizations with HBsAg encapsulated lectinized liposomes and boosting after third week was comparable with the titre recorded after single intramuscular prime and third week boosting with alum-HBsAg. Moreover, lectinized liposomes induced higher sIgA level in mucosal secretions and cytokines level in the spleen homogenates. The results showed that the developed surface modified liposomes could be a potential module for the development of effective mucosal vaccines.
Gupta
Prem N
PN
Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar 470003, Madhya Pradesh, India. premngupta@yahoo.in
Vyas
Suresh P
SP
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects*; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D008024:Ligands; D008081:Liposomes / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D010316:Particle Size; D010581:Peyer's Patches / Q000166:cytology* / Q000187:drug effects; D037121:Plant Lectins / Q000276:immunology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D004337:Drug Carriers; D006514:Hepatitis B Surface Antigens; D007071:Immunoglobulin A, Secretory; D008024:Ligands; D008081:Liposomes; D037121:Plant Lectins; C036850:Ulex europaeus lectins