An efficient targeted drug delivery through apotransferrin loaded nanoparticles.
BACKGROUND
Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin.


RESULTS
Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano) have diameters of 25-50 etam, which increase to 60-80 etam upon direct loading of drug (direct-nano), and showed further increase in dimension (75-95 etam) in conjugated nanoparticles (conj-nano). The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a) localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus) (b) pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c) the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in regression of hepatocellular carcinoma with negligible toxicity to kidney and liver.


CONCLUSIONS
The present study thus demonstrates that the direct-nano is highly efficacious in delivery of drug in a target specific manner with lower toxicity to heart, liver and kidney.
Krishna
Athuluri Divakar Sai
AD
Department of Biochemistry, University of Hyderabad, Hyderabad, India.
Mandraju
Raj Kumar
RK
Kishore
Golla
G
Kondapi
Anand Kumar
AK
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001059:Apoproteins / Q000737:chemistry*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D007700:Kinetics; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D014168:Transferrin / Q000737:chemistry*
D000903:Antibiotics, Antineoplastic; D001059:Apoproteins; D004337:Drug Carriers; D014168:Transferrin; C028284:apotransferrin; D004317:Doxorubicin