1. Investigation of Levan-Derived Nanoparticles of Dolutegravir: A Promising Approach for the Delivery of Anti-HIV Drug as Milk Admixture.
- Author
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Lakshmi Sadhana S, Priya Dharshini K, Ramya Devi D, Naryanan VHB, Veerapandian B, Luo RH, Yang JX, Shanmugam SR, Ponnusami V, Brzezinski M, and Zheng YT
- Subjects
- Humans, Animals, Drug Liberation, Drug Carriers chemistry, Particle Size, Bacillus subtilis drug effects, Spray Drying, Drug Delivery Systems methods, Pyridones chemistry, Oxazines chemistry, Piperazines chemistry, Heterocyclic Compounds, 3-Ring chemistry, Heterocyclic Compounds, 3-Ring administration & dosage, Anti-HIV Agents administration & dosage, Anti-HIV Agents chemistry, Anti-HIV Agents pharmacology, Nanoparticles chemistry, Fructans chemistry, Milk chemistry
- Abstract
Nanoparticles composed of Levan and Dolutegravir (DTG) have been successfully synthesized using a spray drying procedure specifically designed for milk/food admixture applications. Levan, obtained from the microorganism Bacillus subtilis, was thoroughly characterized using MALDI-TOF and solid-state NMR technique to confirm its properties. In the present study, this isolated Levan was utilized as a carrier for drug delivery applications. The optimized spray-dried nanoparticles exhibited a smooth surface morphology with particle sizes ranging from 195 to 329 nm. In the in-vitro drug release experiments conducted in water media, the spray-dried nanoparticles showed 100 % release, whereas the unprocessed drug exhibited only 50 % release at the end of 24 h. Notably, the drug release in milk was comparable to that in plain media, indicating the compatibility. The improved dissolution rate observed for the nanoparticles could be attributed to the solid-state conversion (confirmed by XRD analysis) of DTG from its crystalline to amorphous state. The stability of the drug was verified using Fourier Transform Infra-Red Spectroscopy and Thermogravimetry-Differential Scanning Calorimetry analysis. To evaluate the in-vitro cellular toxicity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted, which revealed the CC
50 value of 88.88 ± 5.10 µg/mL for unprocessed DTG and 101.08 ± 37.37 µg/mL for DTG nanoparticles. These results indicated that the toxicity of the nanoparticles was comparable to the unprocessed drug. Furthermore, the anti-HIV activity of the nanoparticles in human cell lines was found to be similar to that of the pure drug, emphasizing the therapeutic efficacy of DTG in combating HIV., Competing Interests: Declaration of competing interest None., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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