Anti-CD4 antibody and dendrimeric peptide based targeted nano-liposomal dual drug formulation for the treatment of HIV infection

Sadhana P. Mutalik, Shraddha Y. Gaikwad, Gasper Fernandes, Ashwini More, Sanjay Kulkarni, Shaik Mohammad Abdul Fayaz, Karnaker Tupally, Harendra S. Parekh, Smita Kulkarni, Anupam Mukherjee, Srinivas Mutalik

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Abstract

Aims: Development and characterization of LAM and DTG loaded liposomes conjugated anti-CD4 antibody and peptide dendrimer (PD2) to improve the therapeutic efficacy and to achieve targeted treatment for HIV infection. Main methods: A 2-level full factorial design was used to optimize the preparation of dual drug loaded liposomes. Optimized dual drug loaded ligand conjugated liposomes were assessed for their cytotoxicity and cell internalization on TZM-bl cells. Anti-HIV efficiency of the dual drug loaded liposomes were screened for their inhibitory potential in TZM-bl cells and the activities were confirmed using Peripheral Blood Mononuclear Cells (PBMCs). Key findings: The particle size of the optimized dual drug-loaded liposomes was 133.7 ± 4.04 nm, and the spherical morphology of the liposomes was confirmed by TEM analysis. The entrapment efficiency was 34 ± 4.9 % and 54 ± 1.8 % for LAM and DTG, respectively, and a slower in vitro release of LAM and DTG was observed when entrapped into liposomes. The cytotoxicity of the dual drug loaded liposomes was similar to the cytotoxicity of free drug solutions. Conjugation of anti-CD4 antibody and PD2 did not significantly influence the cytotoxicity but it enhanced the uptake of liposomes into the cells. Conjugated dual drug loaded liposomes exhibited better HIV inhibition with lower IC50 values (0.0003 ± 0.0002 μg/mL) compared to their free drug solutions (0.002 ± 0.001 μg/mL). The liposomal formulations have shown similar activities in both screening and confirmatory cell-based assays. Significance: The results demonstrated the cell targeting ability of dual drug loaded liposomes conjugated with anti-CD4 antibody and peptide dendrimer. Conjugated liposomes also improved anti-HIV efficiency of LAM and DTG.

Original languageEnglish
Article number122226
JournalLife Sciences
Volume334
DOIs
Publication statusPublished - 01-12-2023

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology
  • Pharmacology, Toxicology and Pharmaceutics(all)

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