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

Chem Cent J. 2018 May 23;12(1):65. doi: 10.1186/s13065-018-0434-1.


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.

Keywords: Doxorubicin; Oral bioavailability; Oral drug delivery; PEG-PLGA-NPs; Plasma pharmacokinetic.