title: Triple Drug Combination of Zidovudine, Efavirenz and Lamivudine Loaded Lactoferrin Nanoparticles: an Effective Nano First-Line Regimen for HIV Therapy.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India.
authors.forename: Yeruva Samrajya
authors.initials: YS
authors.lastname: Lakshmi
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India. akksl@uohyd.ernet.in.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Kondapi
mesh_terms: D000480:Alkynes; D000818:Animals; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D048588:Benzoxazines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003521:Cyclopropanes; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007781:Lactoferrin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D019259:Lamivudine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000502:physiology; D015215:Zidovudine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004338:Drug Combinations; C109078:lamivudine, zidovudine drug combination; D019259:Lamivudine; D015215:Zidovudine; D007781:Lactoferrin; C098320:efavirenz
keywords: HIV; drug delivery; nanoparticles; pharmacokinetics; zidovudine