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In vitro and in vivo evaluation of dual Clofazimine and Verapamil loaded PLGA nanoparticles

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Abstract

Combination therapy may counter the risk caused by efflux pumps mediated resistance developed by mycobacteria with a concomitant increase of the bactericidal effect of anti-TB drugs. In the present study, combination of two drugs in a nanoformulation was prepared. Clofazimine targets type 2 NADH dehydrogenase of the electron transport chain, and Verapamil inhibits various mycobacterial efflux pumps. The nanotechnology approach was adopted to overcome limitations associated with administration of free form of drugs by using poly (D, L-lactic-co-glycolic acid) as a polymer. Nanoparticles were prepared by oil/water single emulsion solvent evaporation procedure and characterized by various techniques. The results thus highlighted that developed nanoparticles were spherical with nano range size (200-450 nm). Fourier transform infrared spectroscopy revealed successful encapsulation of drugs in developed nanoformulations. Drugs in combination showed higher encapsulation efficiency and percentage drug loading capacity as compared to individual drug nanoformulations. Also, reduced toxicity of nanoformulation was observed in hemolysis assay as compared to free drugs. Ex-vivo analysis demonstrated efficient uptake of rhodamine encapsulated nanoparticles by THP-1 cells, while in-vivo results revealed sustained drug release of nanoformulation as compared to free drugs in combination. Therefore, we were able to achieve development of a single nanoformulation encapsulating Clofazimine and Verapamil in combination. Based on these findings, future studies can be designed to explore the potential of co-encapsulated Clofazimine and Verapamil nanoparticles in management of tuberculosis.

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Authors and Affiliations

  1. Department of Biochemistry, Post Graduate Institute of Medical Education and Research, 160012, Chandigarh, India

    Bhavneet Kaur, Maninder Kaur, Priyanca Ahlawat & Sadhna Sharma

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  1. Bhavneet Kaur
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  2. Maninder Kaur
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  3. Priyanca Ahlawat
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  4. Sadhna Sharma
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Contributions

All authors contributed to the study’s conception and design. Bhavneet Kaur and Maninder Kaur performed material preparation, data collection, and analysis. Priyanca Ahlawat analyzed and interpreted the FTIR data. Bhavneet Kaur wrote the first draft of the manuscript and all authors commented on previous versions of the manuscript. Sadhna Sharma assisted in writing the manuscript and designing the whole study. All authors have read and approved the manuscript.

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Correspondence to Sadhna Sharma.

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An approval was obtained from Institute Animal Ethical Committee (IAEC no.90/IAEC/627) for using Balb/c mice. All experimental procedures were performed in accordance with the institution’s ethical standards or practice.

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Kaur, B., Kaur, M., Ahlawat, P. et al. In vitro and in vivo evaluation of dual Clofazimine and Verapamil loaded PLGA nanoparticles. Ind J Clin Biochem 38, 466–474 (2023). https://doi.org/10.1007/s12291-022-01062-8

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  • DOI: https://doi.org/10.1007/s12291-022-01062-8

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