Mahakal Institute of Pharmaceutical Studies, Ujjain, India.
J Pharm Pharm Sci. 2010;13(4):495-509. doi: 10.18433/j3xk53.
Solid lipid nanoparticles (SLN) have emerged as carriers for therapeutic peptides, proteins, antigens and bioactive molecules. We have explored the potential of SLN as carrier for Hepatitis B surface antigen (HBsAg) by surface modifications to enhance their loading efficiency and the cellular uptake, using subcutaneous route.
Four different formulations of SLN were prepared by solvent injection method and characterized for various physical properties: particle size, surface morphology, shape, zeta potential, polydispersity, X-ray diffraction analysis, release profile and entrapment efficiency. HBsAg loaded SLN were studied for their functional characteristics, in vitro cellular uptake and internalization studies by human dendritic cells, macrophages and fibroblasts, T cell proliferation and TH1/TH2 response. Humoral immune response elicited by subcutaneously administered HBsAg containing SLN formulations were studied in vivo in mice.
Compared to soluble HBsAg; SLN, particularly the mannosylated formulation, showed better cellular uptake, lesser cytotoxicity and induction of greater TH1 type of immune response. They also showed better immunological potential by producing sustained antibody titer.
Mannosylated SLN appears to be promising as carrier for vaccine delivery against hepatitis B as ascertained by in vitro and in vivo studies, however further investigations on humans are required to establish their potential as vaccines against hepatitis B infection.
固体脂质纳米粒（SLN）已成为治疗性肽、蛋白质、抗原和生物活性分子的载体。我们通过表面修饰探索了 SLN 作为乙型肝炎表面抗原（HBsAg）载体的潜力，以增强其载药量和细胞摄取效率，采用皮下途径给药。
采用溶剂注入法制备了 4 种不同配方的 SLN，并对其进行了各种物理性质的表征：粒径、表面形态、形状、Zeta 电位、多分散性、X 射线衍射分析、释放曲线和包封效率。对负载 HBsAg 的 SLN 进行了功能特性、人树突状细胞、巨噬细胞和成纤维细胞的体外细胞摄取和内化研究、T 细胞增殖和 TH1/TH2 反应的研究。在小鼠体内研究了皮下给予含 HBsAg 的 SLN 制剂引起的体液免疫应答。
与可溶性 HBsAg 相比；SLN，特别是甘露糖基化配方，表现出更好的细胞摄取、更低的细胞毒性和诱导更强的 TH1 型免疫应答。它们还通过产生持续的抗体效价显示出更好的免疫潜力。
通过体外和体内研究表明，甘露糖基化 SLN 有望成为乙型肝炎疫苗传递的载体，但需要进一步的人体研究来确定其作为乙型肝炎感染疫苗的潜力。
