title: Biocompatibility, absorption and safety of protein nanoparticle-based delivery of doxorubicin through oral administration in rats.
abstract: Doxorubicin, a potent anticancer drug associated with cardiotoxicity and low oral bioavailability, was loaded into apotransferrin nanoparticles to improve its pharmacological performance. Here, doxorubicin (doxo)-loaded apotransferrin nanoparticles were termed as Apodoxonano, and they were prepared by sol-oil chemistry. The pH-dependent stability of nanoparticles in simulated fluids was evaluated, and the in vitro release was investigated in phosphate-buffered saline. The pharmacokinetic and toxicity studies were conducted in Wistar rats. Nanoparticles have an average size of 75 nm, with 63% entrapment efficiency, at 10 mg w/w of apotransferrin. The particles displayed good pH-dependent stability in the pH range 1.1-7.4, but sensitive at endosomal pH of 5.5, thus facilitating intracellular drug release in endosomes. Multiplex assay showed high transport ability of nano form across epithelial cells (caco-2) when compared to doxo. Moreover, during oral administration, Apodoxonano localizes significantly in esophagus, stomach and small intestine, suggesting that it was absorbed in GI tract through epithelial lining. The drug localization was shown to be significantly lower in the heart reflecting its decreased cardiotoxic nature. The Apodoxonano with a longer bioavailability and a negligible cardiotoxicity can serve as an effective and safe vehicle of drug delivery.
authors.affiliation: Department of Biochemistry, University of Hyderabad, Hyderabad, Andhra Pradesh, India.
authors.forename: Kishore
authors.initials: K
authors.lastname: Golla
authors.forename: Palakolanu S
authors.initials: PS
authors.lastname: Reddy
authors.forename: C
authors.initials: C
authors.lastname: Bhaskar
authors.forename: Anand K
authors.initials: AK
authors.lastname: Kondapi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001059:Apoproteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D001682:Biological Availability; D018938:Caco-2 Cells; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D014168:Transferrin / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism
chemical_list: D001059:Apoproteins; D014168:Transferrin; C028284:apotransferrin; D012710:Serum Albumin, Bovine; D004317:Doxorubicin