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

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

Ahmad N ，Ahmad R ，Alam MA ，Ahmad FJ ，Amir M ，Pottoo FH ，Sarafroz M ，Jafar M ，Umar K ... -  《-》

Improvement of oral efficacy of Irinotecan through biodegradable polymeric nanoparticles through in vitro and in vivo investigations.

Ahmad N ，Alam MA ，Ahmad R ，Umar S ，Jalees Ahmad F ... -  《-》

Preparation and characterization of surface-modified PLGA-polymeric nanoparticles used to target treatment of intestinal cancer.

Ahmad N ，Alam MA ，Ahmad R ，Naqvi AA ，Ahmad FJ ... -  《-》

Biodegradable polymeric nanoparticles for oral delivery of epirubicin: In vitro, ex vivo, and in vivo investigations.

Epirubicin (EPI) is an anthracycline antineoplastic agent, commercially available for intravenous administration only and its oral ingestion continues to remain a challenge. Present investigation is aimed at the development of poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) for oral bioavailability enhancement of epirubicin. Developed formulation revealed particle size, 235.3±15.12 nm, zeta potential, -27.5±0.7 mV and drug content (39.12±2.13 μg/mg), with spherical shape and smooth surface. Cytotoxicity studies conducted on human breast adenocarcinoma cell lines (MCF-7) confirmed the superiority of epirubicin loaded poly-lactic-co-glycolic acid nanoparticles (EPI-NPs) over free epirubicin solution (EPI-S). Further, flow cytometric analysis demonstrated improved drug uptake through EPI-NPs and elucidated the dominance of caveolae mediated endocytosis for nanoparticles uptake. Transport study accomplished on human colon adenocarcinoma cell line (Caco-2) showed 2.76 fold improvement in permeability for EPI-NPs as compared to EPI-S (p<0.001) whereas a 4.49 fold higher transport was observed on rat ileum; a 1.8 fold higher (p<0.01) in comparison to Caco-2 cell lines which confirms the significant role of Peyer's patches in absorption enhancement. Furthermore, in vivo pharmacokinetic studies also revealed 3.9 fold improvement in oral bioavailability of EPI through EPI-NPs. Henceforth, EPI-NPs is a promising approach to replace pre-existing intravenous therapy thus providing "patient care at home".

Tariq M ，Alam MA ，Singh AT ，Iqbal Z ，Panda AK ，Talegaonkar S ... -  《-》

Mucoadhesive chitosan-coated PLGA nanoparticles for oral delivery of ferulic acid.

Lima IA ，Khalil NM ，Tominaga TT ，Lechanteur A ，Sarmento B ，Mainardes RM ... -  《-》