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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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Triple Drug Combination of Zidovudine, Efavirenz and Lamivudine Loaded Lactoferrin Nanoparticles: an Effective Nano First-Line Regimen for HIV Therapy
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Journal Article
Triple Drug Combination of Zidovudine, Efavirenz and Lamivudine Loaded Lactoferrin Nanoparticles: an Effective Nano First-Line Regimen for HIV Therapy
2017
Overview
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 C
max
, >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.
Publisher
Springer US,Springer,Springer Nature B.V
Subject
/ Anti-Retroviral Agents - administration & dosage
/ Anti-Retroviral Agents - chemistry
/ Anti-Retroviral Agents - pharmacokinetics
/ Benzoxazines - administration & dosage
/ Benzoxazines - pharmacokinetics
/ Biomedical and Life Sciences
/ Biomedical Engineering and Bioengineering
/ Drugs
/ Female
/ HIV
/ HIV Infections - drug therapy
/ Human immunodeficiency virus
/ Humans
/ Lactoferrin - administration & dosage
/ Lactoferrin - pharmacokinetics
/ Lamivudine - administration & dosage
/ Lamivudine - pharmacokinetics
/ Male
/ Nanoparticles - administration & dosage
/ Pharmacy
/ Rats
/ Tissue Distribution - physiology
