A long-acting 3TC ProTide nanoformulation suppresses HBV replication in humanized mice

Area of Science:

• Hepatology
• Virology
• Nanomedicine

Background:

• Chronic hepatitis B virus (HBV) infection requires effective antiviral treatments.
• Human immunodeficiency virus (HIV-1) and HBV co-infections necessitate dual-acting, long-acting antivirals.
• Lamivudine (3TC) is a nucleoside analog effective against both HIV-1 and HBV.

Purpose of the Study:

• To evaluate the efficacy of a nanoformulated lipophilic monophosphorylated prodrug of lamivudine (NM23TC) in HBV-infected mice.
• To assess the sustained drug levels and antiviral activity of NM23TC.
• To determine the potential of NM23TC as a long-acting antiviral for HBV.

Main Methods:

• Modification of lamivudine (3TC) into a lipophilic monophosphorylated prodrug (M23TC).
• Nanoformulation of M23TC (NM23TC) to enhance stability and drug delivery.
• Administration of a single intramuscular dose of NM23TC to HBV-infected chimeric liver humanized mice.
• Monitoring of HBV DNA and HBsAg levels in plasma for up to 8 weeks posttreatment.

Main Results:

• A single intramuscular dose of NM23TC (75 mg/kg 3TC equivalents) achieved sustained drug levels.
• NM23TC suppressed HBV replication in humanized mice for 4 weeks.
• Nanoformulation improved drug stability and controlled dissolution.

Conclusions:

• Nanoformulated M23TC (NM23TC) demonstrates significant and sustained suppression of HBV replication.
• This long-acting 3TC nanoformulation is a promising candidate for HBV treatment and prevention.
• Further development of NM23TC is warranted for clinical applications.