Daunorubicin oral bioavailability enhancement by surface coated natural biodegradable macromolecule chitosan based polymeric nanoparticles.

Background: Daunorubicin hydrochloride (DAUN·HCl), due to low oral bioavailability poses the hindrance to be marketed as an oral formulation.

Aim Of The Study: To develop a natural biodegradable macromolecule i.e. Chitosan (CS)-coated-DAUN-PLGA-poly(lactic-co-glycolic acid)-Nanoparticles (NPs) with an aim to improve oral-DAUN bioavailability and to develop as well as validate UHPLC-MS/MS (ESI/Q-TOF) method for plasma quantification and pharmacokinetic analysis (PK) of DAUN.

Results: A particle size (198.3 ± 9.21 nm), drug content (47.06 ± 1.16 mg/mg) and zeta potential (11.3 ± 0.98 mV), consisting of smooth and spherical shape was observed for developed formulation. Cytotoxicity studies for CS-DAUN-PLGA-NPs revealed; a comparative superiority over free DAUN-S (i.v.) in human breast adenocarcinoma cell lines (MCF-7) and a higher permeability i.e. 3.89 folds across rat ileum, as compared to DAUN-PLGA-NPs (p < 0.01) inhuman colon adenocarcinoma cell line (Caco-2). For PK, CS-DAUN-PLGA-NPs as compared to DAUN-S, exhibited a 10.0 fold higher bioavailability in Wister rat's plasma due to presence of a natural biodegradable macromolecule i.e. CS coated on the PLGA-NPs. With regard to bioanalytical method, easy as well as a rapid method for DAUN-plasma quantification was developed as; 2.75 min and 528.49/321.54 m/z for DAUN along with 1.94 min and 544.36/397.41 m/z for IS i.e. Doxorubicin, for elution time and transition, respectively.

Conclusion: A novel natural biodegradable approach used in the preparation of CS coated DAUN-NPs for oral administration of DAUN is reported in this study which is can be utilized as an alternate for intravenous therapy.