title: Curcumin-loaded apotransferrin nanoparticles provide efficient cellular uptake and effectively inhibit HIV-1 replication in vitro.
abstract: BACKGROUND
  Curcumin (diferuloylmethane) shows significant activity across a wide spectrum of conditions, but its usefulness is rather limited because of its low bioavailability. Use of nanoparticle formulations to enhance curcumin bioavailability is an emerging area of research.
  
  
  RESULTS
  In the present study, curcumin-loaded apotransferrin nanoparticles (nano-curcumin) prepared by sol-oil chemistry and were characterized by electron and atomic force microscopy. Confocal studies and fluorimetric analysis revealed that these particles enter T cells through transferrin-mediated endocytosis. Nano-curcumin releases significant quantities of drug gradually over a fairly long period, ∼50% of curcumin still remaining at 6 h of time. In contrast, intracellular soluble curcumin (sol-curcumin) reaches a maximum at 2 h followed by its complete elimination by 4 h. While sol-curcumin (GI(50) = 15.6 µM) is twice more toxic than nano-curcumin (GI(50) = 32.5 µM), nano-curcumin (IC(50)<1.75 µM) shows a higher anti-HIV activity compared to sol-curcumin (IC(50) = 5.1 µM). Studies in vitro showed that nano-curcumin prominently inhibited the HIV-1 induced expression of Topo II α, IL-1β and COX-2, an effect not seen with sol-curcumin. Nano-curcumin did not affect the expression of Topoisomerase II β and TNF α. This point out that nano-curcumin affects the HIV-1 induced inflammatory responses through pathways downstream or independent of TNF α. Furthermore, nano-curcumin completely blocks the synthesis of viral cDNA in the gag region suggesting that the nano-curcumin mediated inhibition of HIV-1 replication is targeted to viral cDNA synthesis.
  
  
  CONCLUSIONS
  Curcumin-loaded apotransferrin nanoparticles are highly efficacious inhibitors of HIV-1 replication in vitro and promise a high potential for clinical usefulness.
authors: Department of Biotechnology, University of Hyderabad, Hyderabad, India.
authors: Upendhar
authors: U
authors: Gandapu
authors: R K
authors: RK
authors: Chaitanya
authors: Golla
authors: G
authors: Kishore
authors: Raju C
authors: RC
authors: Reddy
authors: Anand K
authors: AK
authors: Kondapi
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D001059:Apoproteins / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004279:DNA, Viral / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D016503:Drug Delivery Systems; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D009500:Neutralization Tests; D010316:Particle Size; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000951:Antigens, Neoplasm; D001059:Apoproteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; C028284:apotransferrin; D004250:DNA Topoisomerases, Type II; D003474:Curcumin