Targeted novel surface-modified nanoparticles for interferon delivery for the treatment of hepatitis B

Abstract

The purpose of the present work was to develop hepatitis B surface antigen (HBsAg) surface-adsorbed cationic poly (D,L-lactic-co-glycolic acid) PLGA nanoparticles for interferon alpha (IFNa) delivery targeted to hepatocytes. Cationic PLGA nanoparticles loaded with IFNa were prepared using the double emulsification technique. Delipidated HBsAg was passively adsorbed on the surface of nanoparticles by using the simple dipping and drying method. Surface morphology and size distribution of nanoparticles were analyzed by scanning electron microscopy and dynamic light-scattering method, respectively. The biodistribution behavior of plain and HBsAgcoated 99m Tc-tagged PLGA nanoparticles was also examined followed by intravenous injection. The results revealed that ∼75% of the radioactivity was recovered in the liver after 4 h of injection that was nearly 3-fold greater in magnitude than the plain PLGA nanoparticles. These data demonstrated that the novel formulation of nanoparticles has potential application in hepatic-targeted drug delivery.

In Vitro IFN-α Release From IFN-α- and Pegylated IFN-α-loaded poly(lactic-co-glycolic acid) and Pegylated poly(lactic-co-glycolic acid) Nanoparticles

“…Giri et al [6] synthesised IFN- loaded cationic PLGA nanoparticles with delipidated HBsAg adsorbed on the surface of nanoparticles. Besides PLGA, a number of other micro/nanocarriers such as poly-ε-caprolactone microspheres [7], lipid-based nanostructures [8] and lipid coated aquasomes [9] have also been investigated as human IFN- delivery systems.…”

Drug Delivery Strategies for Antivirals against Hepatitis B Virus

“…Researchers used a double-emulsification technique to prepare HBsAg passively adsorbed onto the surface of cationic PLGA nanoparticles for site-specific delivery of IFN-α to hepatocytes. HbsAg-coated (99m)Tc-labeled PLGA nanoparticles results presented notable liver recovery, in contrast to normal PLGA nanoparticles [ 74 ]. The particle size and hydrophobicity effects of porous PLA and PLGA nanoparticles were assessed on cell-mediated and mucosal immune responses.…”

Cytokine‐Functionalized Synthetic Dendritic Cells for T Cell Targeted Immunotherapies

“…Reducing off‐target stimulation is, therefore, of key importance to diminish the observed dose‐related side effects so that higher therapeutic efficacy of cytokine‐based therapies can be achieved. For IL‐2 and IFNα, these strategies have focused on improving their circulation times, reducing non‐specific binding, localizing delivery, and direct targeting to infected or tumor cells . Although these approaches have indeed shown reduced side effects compared to high‐dose injections of native cytokines, off‐target activation of immune cells can still remain.…”