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Antiretroviral action of Rosemary oil-based atazanavir formulation and the role of self-nanoemulsifying drug delivery system in the management of HIV-1 infection

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Abstract

Atazanavir or ATV is an FDA-approved, HIV-1 protease inhibitor that belongs to the azapeptide group. Over time, it has been observed that ATV can cause multiple adverse side effects in the form of liver diseases including elevations in serum aminotransferase, indirect hyper-bilirubinemia, and idiosyncratic acute liver injury aggravating the underlying chronic viral hepatitis. Hence, there is an incessant need to explore the safe and efficacious method of delivering ATV in a controlled manner that may reduce the proportion of its idiosyncratic reactions in patients who are on antiretroviral therapy for years. In this study, we assessed ATV formulation along with Rosemary oil to enhance the anti-HIV-1 activity and its controlled delivery through self-nanoemulsifying drug delivery system or SNEDDS to enhance its oral bioavailability. While the designing, development, and characterization of ATV-SNEDDS were addressed through various evaluation parameters and pharmacokinetic-based studies, in vitro cell-based experiments assured the safety and efficacy of the designed ATV formulation. The study discovered the potential of ATV-SNEDDS to inhibit HIV-1 infection at a lower concentration as compared to its pure counterpart. Simultaneously, we could also demonstrate the ATV and Rosemary oil providing leads for designing and developing such formulations for the management of HIV-1 infections with the alleviation in the risk of adverse reactions.

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Funding

The Indian Council of Medical Research and ICMR-National AIDS Research Institute, Pune, India, funded this research vide grant no. NARI/SAC/VN/2022-23/2266 (VN and AM).

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology (MIET), NH-58, Delhi-Roorkee Highway, Meerut, 250005, Uttar Pradesh, India

    Shobhit Kumar & Dhananjay Taumar

  2. Division of Virology, ICMR-National AIDS Research Institute, Ministry of Health & Family Welfare, Plot No. 73, ‘G’ Block, MIDC, Bhosari, Pune, 411026, Maharashtra, India

    Shraddha Gaikwad, Ashwini More, Vijay Nema & Anupam Mukherjee

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Contributions

Conceptualization: SK and AM; methodology: SK, DT, AM, and SYG; validation: SK, SYG, and AM; formal analysis: SK, SYG, and AM; investigation: SK, DT, AM, and SYG; resources: SK and AM; data curation: SK, DT, SYG, and AM; writing—original draft preparation: SK, SYG, and AM; writing—review and editing: VN and AM; visualization: SK and AM; supervision: SK and AM; project administration; AM; funding acquisition: SK, VN, and AM. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Anupam Mukherjee.

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Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Animal Ethical Committee (IEAC), MIET, Meerut (UP), India, vide protocol no. IAEC/MIET/2022/49 and the Institutional Ethical Committee (IEC), ICMR-NARI, Pune (MH), India, vide protocol no. NARI/EC/Approval/2022/662. No human specimen was used in this study.

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13346_2023_1492_MOESM1_ESM.tif

Supplementary Fig. 1: A schematic representation of the Zeta potential for different batches of formulation (D1–D8). Measurements were obtained using the electrophoretic mobility method. Here the Zeta potential is negative because of the presence of free unsaturated fats in the oil. (TIF 2395 KB)

13346_2023_1492_MOESM2_ESM.tif

Supplementary Fig. 2: Comparison study of in vitro release profiles of ATV from ATV SNEDDS formulations (D1 and D4) and S-SNEDDS formulations (D1 and D4) up to 360 min. Each point represents the mean ± standard deviation (n = 3). Curves are presented as the percentage of drug release at different time points. (TIF 2011 KB)

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Kumar, S., Taumar, D., Gaikwad, S. et al. Antiretroviral action of Rosemary oil-based atazanavir formulation and the role of self-nanoemulsifying drug delivery system in the management of HIV-1 infection. Drug Deliv. and Transl. Res. (2023). https://doi.org/10.1007/s13346-023-01492-8

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