Encapsulation of ritonavir in solid lipid nanoparticles: in-vitro anti-HIV-1 activity using lentiviral particles.

OBJECTIVES: In this study, ritonavir was entrapped into solid lipid nanoparticles (SLNs) employing two production methods. The prepared SLNs were characterized and antiretroviral activity was investigated for more efficient formulation. METHODS: Ritonavir-loaded SLNs were produced by solvent emulsification evaporation (SE) and double emulsion methods (DE), and the effects of Tween80 and poloxamer188 as external phase surfactant were compared. Prepared SLNs were characterized in terms of size, surface charge, entrapment efficiency (EE), release profile and thermal behaviour. Moreover, the activity of drug-loaded SLNs was investigated on the lentiviral-based pseudo-HIV-1 particles. KEY FINDINGS: The average size of negatively charged SLNs was 170-250 nm with polydispersity index (PDI) of 0.2. The most EE% was about 53.2% achieved by DE method in the presence of poloxamer188. It was found that addition of poloxamer188 in the process led to increased entrapment efficiency and particle size. The in-vitro antiviral experiment showed ritonavir SLNs can actively maintain inhibition of virus production as well as free drug. CONCLUSIONS: In this study, we showed the SLNs not only can encapsulate ritonavir efficiently but also can maintain its antiviral activity and modulate drug release as promising nanocarrier.

A novel dendritic cell-targeted lentiviral vector, encoding Ag85A-ESAT6 fusion gene of Mycobacterium tuberculosis, could elicit potent cell-mediated immune responses in mice.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), leading to high mortality worldwide. It is well-established that cellular immunity plays a critical role to control Mtb infection. Dendritic Cells (DCs) are potent antigen presenting cells, which play an important role to prime cell-mediated immune responses. In vivo targeting of DCs has been shown to induce both strong cellular immunity and protection against tumor challenges. The aim of the present study was not only to assess the immunizing potential of a novel DC-targeted recombinant lentivirus expressing fusion antigen Ag85A-ESAT6 of Mtb, but also to compare it with a recombinant lentivirus with broad cellular tropism expressing the same antigen in mice. The findings demonstrated that our novel recombinant DC-targeted lentivector was able to successfully transduce and express the fusion antigen Ag85A-E6 in vitro and in vivo. Moreover, a single footpad injection of targeted lentivectors could elicit strong T-helper 1 (Th1) immunity against the above mentioned antigen, as indicated by the specific high-level production of IFN-γ and IL-2 using spleen lymphocytes and lymphoproliferative responses. Despite of these promising results, more attempts are required to elucidate the protective and therapeutic efficacy of this approach in future.