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Triple Drug Combination of Zidovudine, Efavirenz and Lamivudine Loaded Lactoferrin Nanoparticles: an Effective Nano First-Line Regimen for HIV Therapy

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ABSTRACT

Purpose

To enhance efficacy, bioavailability and reduce toxicity of first-line highly active anti-retroviral regimen, zidovudine + efavirenz + lamivudine loaded lactoferrin nanoparticles were prepared (FLART-NP) and characterized for physicochemical properties, bioactivity and pharmacokinetic profile.

Methods

Nanoparticles were prepared using sol-oil protocol and characterized using different sources such as FE-SEM, AFM, NanoSight, and FT-IR. In-vitro and in-vivo studies have been done to access the encapsulation-efficiency, cellular localization, release kinetics, safety analysis, biodistribution and pharmacokinetics.

Results

FLART-NP with a mean diameter of 67 nm (FE-SEM) and an encapsulation efficiency of >58% for each drug were prepared. In-vitro studies suggest that FLART-NP deliver the maximum of its payload at pH5 with a minimum burst release throughout the study period with negligible toxicity to the erythrocytes plus improved in-vitro anti-HIV activity. FLART-NP has improved the in-vivo pharmacokinetics (PK) profiles over the free drugs; an average of >4fold increase in AUC and AUMC, 30% increase in the Cmax, >2fold in the half-life of each drug. Biodistribution data suggest that FLART-NP has improved the bioavailability of all drugs with less tissue-related inflammation as suggested with histopathological evaluation

Conclusions

The triple-drug loaded nanoparticles have various advantages against soluble (free) drug combination in terms of enhanced bioavailability, improved PK profile and diminished drug-associated toxicity.

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Abbreviations

3TC or LMV:

Lamivudine

ART:

Antiretroviral therapy

ARV:

Antiretroviral

AZT:

Azidothymidine or Zidovudine

DL:

Drug loading

DMSO:

Di methyl sulfoxide

EE:

Encapsulation efficiency

EFV:

Efavirenz

FLART-NP:

First-Line ART Nanoparticles

FT-IR:

Fourier transform infrared spectroscopy

HPLC:

High Performance Liquid Chromatography

HR:

Hemolysis rate

IC50 :

50% Inhibitory concentration

Lf:

Lactoferrin

NP:

Nanoparticles

NTA:

Nanoparticle tracking analysis

PBS:

Phosphate-buffered saline

sol:

Soluble or free

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ACKNOWLEDGMENTS AND DISCLOSURES

PK (orcid.org/0000-0003-1038-6149) is UGC-NET fellow, YSL is ICMR-SRF fellow. This work was supported by Department of Science and Technology under Nano mission (#SR/NM/NS-1127/2011). AKK is recipient of FRPS BSR UGC one time grant. PK and AKK conceived and designed the experiments. PK and YSL did the experiments and analyzed the data. AKK and PK wrote the manuscript. The authors report no conflicts of interest in this work

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Authors and Affiliations

  1. Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India

    Prashant Kumar, Yeruva Samrajya Lakshmi & Anand K Kondapi

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  1. Prashant Kumar
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  2. Yeruva Samrajya Lakshmi
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  3. Anand K Kondapi
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Correspondence to Anand K Kondapi.

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Kumar, P., Lakshmi, Y.S. & Kondapi, A.K. Triple Drug Combination of Zidovudine, Efavirenz and Lamivudine Loaded Lactoferrin Nanoparticles: an Effective Nano First-Line Regimen for HIV Therapy. Pharm Res 34, 257–268 (2017). https://doi.org/10.1007/s11095-016-2048-4

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