Enhancement of oral bioavailability of doxorubicin through surface modified biodegradable polymeric nanoparticles

Abstract Background Doxorubicin hydrochloride (DOX·HCl), an anthracycline glycoside antibiotic, exhibits low oral bioavailability due to active efflux from intestinal P-glycoprotein receptors. The oral administration of DOX remains a challenge hence; no oral formulation for DOX is marketed, till date. Aim of the study To improve the oral bioavailability of DOX through, preparation of a nanoformulation i.e. PEGylated-doxorubicin(DOX)-loaded-poly-lactic-co-glycolic acid (PLGA)-Nanoparticles (NPs) and to develop and validate an ultra-high performance liquid chromatography electrospray ionization-synapt mass spectrometric bioanalytical method (UHPLC/ESI-QTOF–MS/MS) for plasma (Wistar rats) DOX quantification. Materials and methods For chromatography, Waters ACQUITY UPLC™ along with a BEH C-18 column (2.1 mm × 100 mm; 1.7 μm), mobile phase conditions (acetonitrile: 0.1% formic acid::1:1 v/v) and flow rate (0.20 ml/min) was used. For analyte recovery from rat plasma, a liquid–liquid extraction method (LLE), using Acetonitrile: 5 mM ammonium acetate in a ratio of 6:4 v/v at pH 3.5, was used. Results Nanoformulation with a particle size (183.10 ± 7.41 nm), zeta potential (− 13.10 ± 1.04 mV), drug content (42.69 ± 1.97 µg/mg) and a spherical shape and smooth surface was developed. An elution time of 1.61 and 1.75 min along with a transition at m/z 544.42/397.27 and 528.46/321.41 were observed for DOX and internal standard (IS) Daunorubicin, respectively. In addition, a linear dynamic range with r2 ≥ 0.9985 over a concentration range of 1.00–2500.0 ng/ml was observed for different processes and parameters used in the study. Similarly a marked improvement i.e. 6.8 fold was observed, in PEGylated-DOX-PLGA-NPs as compared to DOX-S, in pharmacokinetics studies. Conclusion The promising approach of PEGylated-DOX-PLGA-NPs may provide an alternate to intravenous therapy for better patient care