Introduction: Hepaitis b is one of the most common hepatic infectious disease that caused by hepatitis b virus that can lead to early death caused by cirrhosis, liver failure or cancer and thus is considered a health problem.
About 350 millions of world population are affected by HBV chronic infection and about 378 millions are the chronic carriers of this disease an every year there is a bout 620000 mortality regarding to HBV.
Iran as other middle east countries has medium prevalence (within range of 1.7% to 5%) of chronic infection of hepatitis B and more than 35% of Iranians are exposed to this infection.
Due to the adverse effects, long anti hepatitis drugs use and occurrence of drug resistance to them, the best approach in This disease is prophylaxis of disease by vaccination.
The vaccine formulation that are available in the pharmaceutical market today, contains surface antigen of hepatitis b with aluminum solutes as adjuvant. that due to insufficient immunogenicity it should be injected and reminded three times. Among the side effects of alum are increasing of IgE production, allergic and neurotoxic reactions and granuloma . Naturally low doses of alum excreted by kidneys but when kidneys function is reduced the alum accumulates in the body and causes neurological syndrome, dialysis dementia, Alzheimer’s disease and amyotrophic lateral sclerosis also due to unstimulating of Th by alum sufficient immune reaction don’t created and hepatitis b infection is not completely prevented by vaccines available today so vaccination system improvement (adjuvant), is considered a international necessity.
The nanoparticles because of their small size, easily absorbed by phagocyte cells and lymphatic tissue and make the humoral and cellular immune system more active and also their surface modification is possible with specific ligand which provides selective and targeted stimulation of the immune system.
In this study, due to proper stability, biocompatibility, biodegradability, controlled release condition, simple method and low cost of production, compared to other polymeric and lipid nanoparticles, as HbsAg carrier in the vaccination system and adjuvants, solid lipid nanoparticles are used.
The purpose of this study is the vaccination system improvement to reduce that side effects and increase that performance until the product can be used to enhance the health and patient compliance.
Methods: The hepatitis b surface antigen was provided from iran institute Pasteur product line and then solid lipid nanoparticles were prepared by high pressure microemultion-homogenization method and their surface modified by mannan ligand. The percentage of HB encapsulated in the SLNs was determined using a centrifugation method then the amount of free HB in the supernatant was measured using a UV Spectrophotometer in 218 nm. The in vitro release of HB from the optimized HB-SLN formulation was evaluated using a dialysis membrane then The concentration of HB in samples was determined by UV Spectrophotometer at 218 nm. The nanoparticles size and PDI measured by Zetasizer instrument and Scanning electron microscopy used to analyze the morphological characterizationh of nanoparticles
Results: After doing numerous tests it was determined that this HbsAg containing mannosylated SLNs with 210 nm in size and PDI of 0.218 are suitable for IV, IM and transdermal injection and have good physicochemical properties. their antigen loading capacity is 73.1% and entrapment efficacy is 74%. They also release antigen by 86% that antigen release from this SLNs in body follow zero order pattern.The formulation in terms of stability in size, PH and physicochemical properties in accelerated conditions based on tests performed in accordance with ICHQIA(R) international guidelines is good and acceptable
Conclusion: Due to the result of this study HBsAg containing mannosylated SLNs are good candidate for vaccination system and can be used for increase patient acceptability and health. Mannosylated SLN appears to be promising as carrier for vaccine delivery against hepatitis B however further investigations on humans are required to establish their potential as vaccines against hepatitis B infection.
Keywords: formulation, vaccine, hepatitis b surface antigen, solid lipid nanoparticles